CA2396040A1 - Novel bacterial genes and proteins that are essential for cell viability and their uses - Google Patents

Abstract

The present invention provides novel bacterial genes and their encoded polypeptides thereof which are essential for bacterial cell viability, and their uses.

Description

NOVEL BACTERIAL GENES AND PROTEINS THAT ARE ESSENTIAL FOR
CELL VIABILITY AND THEIR USES
10 Throughout this application various publications are referenced. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains.
FIELD OF THE INVENTION
The present invention relates generally to nucleotide sequences, and polypeptides encoded by the sequences, that are essential for bacterial viability, and to methods of using the nucleotide and polypeptide sequences.
BACKGROUND OF THE INVENTION
Bacterial genera, such as Streptococcus, Staphylococcus, Pseudomorcas, Ye~sinia, Salmonella, and Ente~~obacte~, are the cause of numerous afflictions in humans and animals. Bacterial infection can lead to serious health conditions, including pneumonia, osteomyelitis, meningitis, sinusitis, otitis, cystitis, and even food poisoning. Typically, these infections can be treated with standard antimicrobial agents such as antibiotics.
However, the emergence of pathogenic bacterial strains that are resistant to antibiotics has risen alarmingly in the past two decades. This situation has created an urgent need for the development of new antimicrobial agents.
One strategy for developing new antimicrobial agents is to identify bacterial gene sequences that encode gene products that are essential for bacterial cell viability and develop and/or identify agents which inhibit the function of the gene product.
DNA
sequencing technology has advanced from sequencing one gene at a time to sequencing entire genomes, the sum of all genes in an organism. With the. recent arrival of bacterial genomic information, it is now possible to compare multiple bacterial genomes in an attempt to identify genes that encode conserved gene products. In this manner, one skilled in the art may identify a set of conserved bacterial genes, including a subset of genes that are essential for bacterial cell viability. The essential gene is then used as a starting point to develop therapeutic agents that inhibit or inactivate the product of the essential gene.
The availability of DNA sequence information for multiple microbial genomes is. a recent development. The public release of the first complete genome, Haemopliilus ihflue~zae (Fleischmann, R.D., et al. 1995 Science 269:496-512 ), was followed in rapid succession by a number of public and private genome sequencing programs. Presently, some completely sequenced bacterial genomes have been published, and over 100 other sequencing projects are underway (Blattner, F.R., et al., 1997 Science 277:1453-74;
Ferretti, J.J., et al., 1997 Adv Exp Med Biol 418:961-963; Koonin, E.V., et al., 1996 .
Methods Enzymol 266:295-322). Analyses of these data indicate that approximately 46°1° of putative bacterial genes are of unknown function having no attributable function.
Others have- pursued various strategies to identify bacterial genes that are essential for viability. These strategies include: identifying genes that are expressed by the bacteria when present in the infected host (Hensel; M., et al., 1995 Science 269:400-3), identifying essential genes by isolating temperature sensitive mutants (Schmid, M.B., et al., 1998 Curs Opih Chem Biol 2:529-34), and identifying genes in pathways known from prior physiological studies to be essential (Skarzynski, T. et al., 1996 Structure 1996 4:1465-74) There continues to be a need to identify bacterial genes that encode gene products that are essential for cell viability, such as cell replication, growth, and survival.
These genes and their encoded gene products can be used as a starting point towards identifying agents that inhibit functions essential for cell viability, thereby causing bacterial cell stasis or death (e.g., antibacterial agents).
The present invention provides experimental identification of novel, conserved essential genes (ceg) from bacteria and their encoded protein products. The ceg genes axe considered essential to cell viability because disruption of an endogenous ceg gene results in lethality of a bacterial cell (e.g., as determined by failure to recover viable chloramphenicol-resistant colonies, as described herein). . Thus, the gene products encoded by these genes are potentially valuable targets for chemotherapeutic intervention of bacterial infections.
The ceg nucleotide sequences of the invention were obtained by large-scale computational comparisons of multiple genome sequences to identify conserved protein coding regions, followed by gene disruption to identify cegs. The conservation of protein sequences in many cases is believed to reflect the higher level conservation of common biochemical pathways essential for bacterial function and viability.
SUMMARY OF THE INVENTION
The acronyms "CEG" and "ceg" stand for Conserved Essential Gene. For convenience, the italicized term ceg refers herein to ceg nucleotide sequences. The capitalized term CEG
refers herein to CEG polypeptide sequences.
Embodiments of the ceg nucleotide sequences and the CEG polypeptide sequences are designated CFEs which stands for CEG For Expression. The CFEs are polypeptides resulting from expression of the ceg nucleotide sequence.
The _present invention provides isolated nucleotide sequences of conserved essential genes from bacteria, designated ceg. The invention also provides recombinant nucleic acid molecules including the ceg sequences of the invention, and methods of uses thereof.
Examples of nucleic acid molecules having ceg sequences are described in SEQ
ID

NOS.: 1-113. The invention further provides isolated polypeptides and recombinant polypeptides having the CEG sequences of the invention, and methods of uses thereof.
Examples of polypeptides having CEG sequences are described in SEQ ID NOS.:114-226.
The ceg sequences of the present invention are DNA or RNA. Further, the invention includes nucleic acid molecules that are identical or nearly identical ~(e.g., similar) with the ceg sequences of the invention. The invention additionally provides polynucleotide sequences that hybridize under stringent conditions to the ceg sequences of the invention.
A further embodiment provides polynucleotide sequences which are complementary to the ceg sequences of the invention. Yet another embodiment provides ceg nucleic acid molecules that are labeled with a detectable marlcer. Another embodiment provides recombinant nucleic acid molecules, such as a vector or a fusion molecule, including the ceg sequences of the invention.
. ' The present 'invention provides various ceg sequences, fragments thereof having essential gene activity, and related molecules such as antisense molecules, oligonucleotides, peptide nucleic acids (PNA), fragments, and portions thereof.
The present invention relates to the inclusion of the polynucleotides encoding CEG gene products, such as CEG polypeptides, in an expression vector which can be used to transform host cells or organisms. Such transgenic hosts are useful for the production of CEG gene products for the development of antibacterial agents such as antibiotics.
The invention further provides substantially purified CEG gene products, and uses thereof.
The invention also relates to pharmaceutical compositions comprising antisense molecules capable of disrupting expression of ceg sequences, agonists, antagonists or inhibitors of CEG gene products, and antibodies reactive against the CEG
polypeptides.

These compositions are useful for preventing the growth or survival of bacteria, for example, in the treatment of conditions associated with bacterial infections.
BRIEF DESCRIPTION OF THE FIGURES
Figure 1: A schematic representation of the gene disruption assay, as described .in Example 3, i~c, f~a. A) A recombinant vector undergoing homologous recombination with the host genome. B) The result of homologous recombination.
Figure 2: A -schematic representation of the polarity test for operons, as described in Examples 2 and 3, infi°a. A) The recombinant vector undergoing homologous recombination with the host genome. B) Case 1: one possible result of homologous recombination; the downstream Gene B has an independent promoter. C) Case 2;
another possible result of homologous recombination; the downstream Gene B does not have an independent promoter.
Figure 3: Purification of 2CFE 75, as described in Example 6, ihfi°a.
A) Fractionation profile of 2CFE 75 eluted from a Ni-NTA column. B) Gel electrophoresis of pooled fractions of CFE 75. C) Non-denaturing gel electrophoresis to determine oligo form of 2CFE 75.
Figure 4: Fractionation profile of 2CFE 3 eluted from a hydroxyapatite column, as described in Example 7, infra.
Figure 5: The biosynthesis pathway of Coenzyme A which starts with phosphorylation of pantothenate.
Figure 6: Circular dichroism spectra of 2CFE 101 and 103, as described in Example 10, infra. A) Circular dichroism spectra of 2CFE 101 and 103 at 25 degrees C. B) Circular dichroism thermal melt spectra of 2CFE 101 and 103 at a range of zero to 100 degrees C.

Figure 7: Circular dichroism spectra of aggregate and monomer pools of 2CFE
101 and 103, as described in Example 10, infi°a. A) Circular dichroism spectra of aggregate and monomer pools of 2CFE 101 and 103 at 25 degrees C. B) Circular dichroism thermal melt spectra of aggregate and monomer pools of 2CFE 1 O l and 103 at a range of zero to 100 degrees C.
Figure 8: Absorbance spectra of.pantothenate-dependent production of ADP, as described in Example 10, it~fr°a.
Figure 9: The results of size exclusion chromatography and gel electrophoresis showing the oligomeric forms of 2CFE 21 and 39, as described in Example 11, ihfi~a. Lanes 1-6 contain .2CFE 21, lane 7 is a molecular weight marker, lanes 8-10 contain 2CFE 39 Figure 10: Gel electrophoresis of a helicase reaction using 2CFE 21 and 39 and radiolabeled synthetic Holliday Junction template, 'as described in Example 11, ihfi~a, Lane 1 contains the synthetic Holliday Junction template; lane 2 contains the synthetic duplex; lane 3 contains a single-stranded template; lane 4 contains the helicase reaction using 2CFE 39;
lane 5 contains the helicase reaction using 2CFE 21; lanes 6-8 contain the helicase reaction using 2CFE 39 and 21 at varying concentrations (e.g., 1, 2, and 3 ~,M each);
and lane 9 contains the helicase reaction using 2 ~.M each 2CFE 39 and 21 in the presence of ethidium bromide.
Figure 11: A graph depicting the results of the helicase reaction which were monitored by measuring the unquenching of the Holliday Junction templates with time, as described in Example 11, infi°a.
Figure 12: Capillary electrophoresis results of 2CFE 8 with and without ssDNA, as described in Example 12, infra. A) Electropherogram of 2CFE 8 alone: B) Electropherogram of 2CFE 8 in the presence of a 32-nucleotide single-stranded oligomer.
Figure 13: Gel mobility shift assay of 2CFE 8, and 2CFE 8 in the presence of a single-stranded 32-mer, as described in Example 12, ihfi~a. A) An ethidium bromide-stained, native, polyacrylamide gel containing 2CFE 8, and 2CFE 8 in the presence of a 32-mer. B) The same native, polyacrylamide gel stained with Coomassie.
Figure 14: The N-acetyl glucosamine pathway putatively mediated .by 2CFE 3 and 86, as described in Example 13, i~, f~a.
Figure 15: Capillary electrophoresis results of 2.CFE 3 with and without putative substrates, as described in Example 13, infra.. A) Electropherogram of 2CFE 3 with ,and without glucosamine-1-phosphate. B) Electropherogram of 2CFE 3 with and without D-glucose-1-phosphate. C) Electropherogram of 2CFE 3 alone, 2CFE 3 and glucose-1-phosphate, and 2CFE 3 and glucose-6-phosphate. D) Electropherogram of 2CFE 3 alone or in the presence of glucosamine-1-phosphate, glucosamine-6-phosphate, D-glucose, D(+) galactose, and a,-D-glucose-1-phosphate.
Figure 16: Capillary electrophoresis results of FITC-derivitized 2CFE 3 polypeptide with and without D-glucosamine-6-phosphate (substrate) to produce the product D-glucosamine-1-phosphate, using laser-induced fluorescence, as described in Example 13, infra.
Electropherogram of D-glucosamine-6-phosphate (putative substrate), 2CFE 3 reacted with D-glucosamine-6-phosphate, and the product glucosamine-1-phhosphate.
Figure 17: Gel electrophoresis of 2CFE 86 eluted from an Ni-NTA column, as described in Example 13, infra.
Figure 18: HPLC analysis of a coupled reaction including 2CFE 3, 2CFE 86, and D=
glucosamine-6-phosphate to produce the product, UDP-N-acetylglucosamine-1-phosphate (UDPAG), as described in Example 13, infra.
Figure 19: A fatty acid biosynthesis pathway.

Figure 20: Size exclusion chromatography to determine the molecular weight and oligomeric form of 2CFE 34, as described in Example 14, infi°a..
Selected eluted samples were sized by gel electrophoresis.
Figure 21: Gel electrophoresis of 2CFE 41 eluted from a Ni-NTA colurim, as described in Example 15, i~fi°a.
Figure 22: Capillary electrophoresis results of 2CFE 40, 41, and 46, as described in Example 15, infra.
Figure 23: Depicts a schematic diagram of a ligand which binds 2CFE 34. The ligand is 2-phenyl-N-(3 corboxyl-4hydroxyphenyl) azabicyclo [4.3.0] riona-2, 8-dime.
Figure 24: Depicts a schematic diagram of a ligand which binds 2CFE 43. The ligand is N-(3, 5-dinitrobenzyl)-7-trifluoromethyl benza diaza furanolactone.
Figure 25: Depicts a schematic diagram of a ligand which binds 2CFE 43. The ligand is 2-amino (N-para-methylphenyl sulfonamide)-3-phenylpropianic acid.
Figure 26: A nucleic acid sequence of 2CFE1 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 27: A nucleic acid sequence of 2CFE2 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 28: A nucleic acid sequence of 2CFE3 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 29: A nucleic acid sequence of 2CFE4 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.

Figure , 30: A nucleic acid sequence of 2CFE5 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 31: A nucleic acid sequence of 2CFE6 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 32: A nucleic acid sequence of 2CFE7 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 33: A nucleic acid sequence of 2CFE8 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 34: A nucleic acid sequence of 2CFE9 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 35: A nucleic acid sequence of 2CFE10 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 36: A nucleic acid sequence of 2CFE11 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 37: A nucleic acid sequence of 2CFE12 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 38: A nucleic acid sequence of 2CFE13 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 39: A nucleic acid sequence of 2CFE14 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.

Figure 40: A nucleic acid sequence of 2CFE15 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 41: A nucleic acid sequence of 2CFE16 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 42: A nucleic acid sequence of 2CFE17 deposited with the American Type Culture Collection as ATCC designation on .December 20, 2000.
Figure 43: A nucleic acid sequence of 2CFE19 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 44: A nucleic acid sequence of 2CFE21 deposited with the American Type Culture Collection as ATCC designation ~ on December 20, 2000.
Figure 45: A nucleic acid sequence of 2CFE24 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 46: A nucleic acid sequence of 2CFE25 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 47: A nucleic acid sequence of 2CFE26 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 48: A nucleic acid sequence of 2CFE27 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 49: A nucleic acid sequence of 2CFE28 deposited with the Arrierican Type Culture Collection as ATCC designation on December 20, 2000.

Figure 50: A nucleic acid sequence of 2CFE29 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 51: A nucleic acid sequence of 2CFE30 deposited with the American Type Culture Collection as ATCC designation ' ' on December 20, 2000.
Figure 52: A nucleic acid sequence of 2CFE31 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 53: A nucleic acid sequence of 2CFE32 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000:
Figure 54: A nucleic acid sequence of 2CFE33 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 55: A nucleic acid sequence of 2CFE34 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 56: A nucleic acid sequence of 2CFE35 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 57: A nucleic acid sequence of 2CFE36 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 58: A nucleic~acid sequence of 2CFE37 deposited with the American Type Culture Collection as ATCC designation on December 20; 2000.
Figure 59: A nucleic acid sequence of 2CFE38 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.

Figure 60: A nucleic acid sequence of 2CFE39 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 61: A nucleic acid sequence of 2CFE40 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 62: A nucleic acid sequence of 2CFE41 deposited with the American Type Culture Collection as ATCC designation ' on December 20, 2000.
Figure 63: A nucleic acid sequence of 2CFE42 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 64: A nucleic acid sequence of 2CFE43 deposited with the American Type Culture Collection as ATCC designation ~ on December 20, 2000:
Figure 65: A nucleic .acid sequence of 2CFE44 deposited with the.American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 66: A nucleic acid sequence of 2CFE45 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 67: A nucleic acid sequence of 2CFE46 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 68: A nucleic acid sequence of 2CFE47 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 69: A nucleic acid sequence of 2CFE48 deposited with the American Type Culture Collection as ATCC designation . on December 20, 2000.

Figure 70: A nucleic acid sequence of 2CFE49 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 71: A nucleic acid sequence of 2CFE50 deposited with the American Type Culture Collection as ATCC designation ~ on December 20, 2000.
Figure 72: A nucleic acid sequence of 2CFE51 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 73: A~nucleic acid sequence of 2CFE52 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 74: A nucleic acid sequence of 2CFE53 deposited with the American Type .Culture Collection as ATCC designation on December 20, 2000.
Figure 75: A nucleic acid sequence of 2CFE54 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 76: A nucleic acid sequence of 2CFE55 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 77: A nucleic acid sequence of 2CFE56 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 78: A nucleic acid sequence of 2CFE57 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 79: A nucleic acid sequence of 2CFE58 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.

Figure 80; A nucleic acid sequence of 2CFE59 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 81: A nucleic acid sequence of 2CFE60 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 82: A nucleic acid sequence of 2CFE61 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 83: A nucleic acid sequence of 2CFE62 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 84: A nucleic acid sequence of 2CFE64 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 85: A nucleic acid sequence of 2CFE65 deposited with the American Type Culture Collection as ATCC designation on December 20,,2000.
Figure 86: A nucleic acid sequence of 2CFE66 deposited with the American Type Culture Collection as ATCC designation ~ on December 20, 2000.
Figure 87: A nucleic acid sequence of 2CFE67 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 88: A nucleic acid sequence of 2CFE68 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 89: A nucleic acid sequence of 2CFE69 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.

Figure 90: A nucleic acid sequence of 2CFE70 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 91: A nucleic acid sequence of 2CFE71 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 92: A nucleic acid sequence of 2CFE72 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 93: A nucleic acid sequence of 2CFE75 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 94:. A nucleic acid sequence of 2CFE76 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 95f. A nucleic acid sequence of 2CFE78 deposited with the American Type Culture Collection as ATCC designation ~ on December 20, 2000.
Figure 96: A nucleic acid sequence of 2CFE79 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 97: A nucleic acid sequence of 2CFE80 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 98: A nucleic acid sequence of 2CFE81 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 99: A nucleic acid sequence of 2CFE82 deposited with the American Type .Culture Collection as ATCC designation on December 20, 2000.

Figure 100: A nucleic acid sequence of 2CFE83 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 101: A nucleic acid sequence of 2CFE84 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 102: A nucleic acid Sequence of 2CFE85 deposited with the Arizerican Type Culture Collection as ATCC designation on December 20, 2000.
Figure 103: A nucleic acid sequence of 2CFE86 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 104: A nucleic acid sequence of 2CFE87 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 105: A nucleic acid sequence of 2CFE88 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 106: A nucleic acid sequence of 2CFE89 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 107: A nucleic acid sequence of 2CFE90 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 108: A nucleic acid sequence of 2CFE91 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 109: A nucleic acid sequence of 2CFE92 deposited with the American Type Culture Collection as ATCC designation ' on December 20, 2000.

Figure 110: A nucleic acid sequence of 2CFE94 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 111: A nucleic acid sequence of 2CFE95 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 112: A nucleic acid sequence of 2CFE96 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 113: A nucleic acid sequence of 2CFE97 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 114: A -nucleic acid sequence of 2CFE99 deposited with the American Type Culture Collection as ATCC designation . on December 20, 2000.
Figure 115: A nucleic acid sequence of 2CFE101 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 116: A nucleic acid sequence of 2CFE102 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 117: A nucleic acid sequence of 2CFE103 deposited with the Arizerican Type Culture Collection as ATCC designation on December 20, 2000.
Figure 118: A~ nucleic acid sequence of 2CFE104 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 119: A nucleic acid sequence of 2CFE105 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.

Figure 120: A nucleic acid sequence of 2CFE106 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 121: A nucleic acid sequence of 2CFE107 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 122: A. nucleic acid sequence of 2CFE108 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 123: A nucleic acid sequence of 2CFE109 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 124: A nucleic acid sequence of 2CFE111 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 125: A nucleic acid sequence of 2CFE112 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 126: A nucleic acid sequence of 2CFE113 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 127: A nucleic acid sequence of 2CFE114 deposited With the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 128: A nucleic acid sequence of 2CFE115 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 129: A nucleic acid sequence of 2CFE116 deposited with the American Type Culture Collection as ATCC designation ' on December 20, 2000.

Figure 130: A nucleic acid sequence of 2CFE117 deposited with the American Type Culture Collection as ATCC designation on December 20, 2000.
Figure 131: Schematic structures of alkyloids which are ligands, for example, of 2CFE42.
DETAILED DESCRIPTION OF THE INVENTION
Definitions All scientific and technical terms used in, this application have meanings commonly used in the art unless otherwise specified. As used in this application; the following words or phrases have the meanings specified:
As used herein, a ceg nucleic acid molecule is said to be "isolated" when the nucleic acid molecule is substantially separated from contaminant nucleic acid molecules that encode polypeptides other than CEGs. Additionally, isolated nucleic acid molecule refers to any RNA or DNA sequence obtained from a natural source, or constructed by recombinant methods, or synthesized. A skilled artisan can readily employ nucleic acid isolation procedures to obtain an isolated nucleic acid molecule having ceg sequences.
The term "ceg" includes all isolated forms of ceg nucleotide and CEG amino acid sequences disclosed herein. The ceg sequences encode gene products that have essential biological functions in bacterial cells, such as, for example, nucleotide biosynthesis, amino acid biosynthesis, DNA replication, RNA transcription, protein translation, DNA
recombination, DNA repair, biosynthesis of cofactors (e.g., Coenzyme ~A), biosynthesis of prosthetic groups, cellular processes (e.g., chaperones, cell division, and polypeptide secretion), energy metabolism (e.g., pentose phosphate pathway, glycolysis, gluconeogenesis), fatty acid biosynthesis, cell wall biosynthesis, andlor biosynthesis of purines, pyrimidines, nucleosides, and nucleotides. Accordingly, the gene products of the ceg nucleotide sequences are required for viability of bacterial cells. The term "ceg" also includes eariants having nucleotide sequence similarity to the disclosed ceg sequences, including sequences isolated from various bacterial genera and species, allelic variants, mutant variants, and ceg variants that encode conservative and non-conservative amino acid substitutions. The present invention also provides for all ceg sequences generated by recombinant DNA technology, including complementary sequences, ceg sequences that hybridize to the sequences of the invention at high stringency hybridization conditions, fusion genes comprising a ceg sequence, and codon usage variants.
The term "essential genes" refers to a nucleotide sequence that encodes a gene product having a function which is required for cell viability. The term "essential protein" refers to a polypeptide that is encoded by an essential gene and has a function that is required for cell viability. Accordingly, a mutation that disrupts the function of the essential gene or essential proteins results in a loss of viability of cells harboring the mutation.
"Non-essential genes" or "non-essential proteins" refer to genomic information or the proteins) or RNAs encoded therefrom which, when disrupted by a mutation, do not result in a loss of viability of cells harboring said mutation under defined laboratory conditions.
As used herein, a nucleotide sequence is said to be "identical" to another reference sequence when both nucleotide sequences are exactly alike.
As used herein, a nucleotide sequence is said to be "similar" to another reference sequence when a comparison of the two sequences shows that they have a low level of sequence differences. For example, two sequences are considered to be similar to each other when the percentage of nucleotides that are shared between the two sequences is between about 70 % to 99.99% over the entire length of the two sequences.
As used herein .an amino acid sequence is said to be "similar" to another reference sequence when a comparison of the two sequences shows that they have a love level of sequence differences. For example, two sequences are considered to be similar to each other when the percentage of amino acids that are shared between the two sequences may be between about 30% to 100% identity over the entire length of the two sequences.
As used herein, an "allele" or "allelic sequence" is an alternative form of the naturally-occurring ceg sequence. Alleles result from a mutation, that changes the nucleotide sequence, and generally produce altered mRNAs or polypeptides whose structure or function may or may not be altered.
"Substantially purified" as used herein means a specific isolated nucleic acid or protein, or fragment thereof, in which substantially all contaminants (i.e. substances that differ from said specific molecule) have been separated from said nucleic acid or protein.
In a host cell, an "endogenous" sequence as~ used herein means a nucleic acid sequence that is naturally-occurring and resides within the host genome.
In a host cell, an "exogenous" sequence as used herein means an isolated nucleic acid sequence that is introduced into the host cell, using any one of a variety of introduction methods, such as transfection, electroporation, cationic lipid or salt treatment methods.
"Knockout mutant" or "knockout mutation" as used herein refers to an ivc vitro engineered disruption of a region of endogenous chromosomal DNA (e.g., disruption of the genome), typically within a protein coding region. A knockout mutation can be generated by inserting an exogenous DNA sequence into the homologous endogenous sequence: A
knockout mutation occurring in a protein coding region is expected to disrupt normal expression of the protein coding region. This usually leads to loss of the function provided by the protein.
In order that the invention herein described may be more fully understood, the following description is set forth.

A) MOLECULES OF THE INVENTION
1.) CEG NUCLEIC ACID MOLECULES
The present invention provides isolated and recombinant ceg nucleic acid molecules and fragments thereof, and related molecules, such as sequences complementary to ceg sequences or a portion thereof, and those that hybridize to the nucleic acid molecules of the invention.
The ceg polynucleotide sequences, also referred to herein as nucleic acid molecules of the invention, are preferably in isolated form, including DNA, RNA, DNA/RNA
hybrids, and related molecules, and fragments thereof. Specifically contemplated are genomic DNA, ribozymes, and aritisense molecules, as well as nucleic acid molecules based on an alternative backbone or including alternative bases, whether derived from natural sources or.
synthesized. Embodiments of particular ceg polynucleotide and amino acid sequences include, but are not limited to, the sequences described in Tables I and II
(e.g., SEQ ID
NOS:1-113, 114-226 and SEQ ID NOS: 227-339, 340-452, respectively). The ceg polynucleotide and amino acid sequences were designated cfe which stands for CEG For Expression.
Biological samples of the 2CFE nucleic acid molecules (e.g., SEQ ID NOS: 227-331) were deposited on December 20, 2000 with the American Type Culture Collection (ATGC), 10801. University Blvd., Manassas, VA 20110-2209 TABLE I
CFE DesignationSEQ. ID NO. SEQ. ID NO. POLARITY
(Nucleotide) (Polypeptide) CFE 1 1 114 +

CFE 4 4 117 ~ +

CFE 6 6 I19 +

TABLE I
CFE Designation SEQ. ID NO. SEQ. POLARITY
(Nucleotide) ID
NO.
(Polypeptide) CFE 8 ~ 8 121 CFE 9 - 9 122 +

CFE 10 10 123 +

CFE 11 11 124 +

CFE 12 12 125 +

CFE 14 14 127 +

CFE 19 18 131 +

CFE 25 ' 21 134 +.

CFE 27 23 136 +

CFE 30 26 ' 139 -CFE 31 27 140 +

CFE 32 28 141 +

CFE 34 30 143 +

CFE 3 5 31 144 +

CFE 36 32 145 +

CFE 38 34 147 +

CFE 41 37 ~ 150 -CFE 43 _ 39 152 CFE 44 40 ~ 153 . +

TABLE I
CFE Designation SEQ. ID NO. SEQ. POLARITY
(Nucleotide) ID
NO.
(Polypeptide) CFE 47 43 156. -CFE 49 45. 158 +

CFE 50 46 159 +

CFE 51 47 160 +

CFE 53 49 162 +

CFE 54 50 163 +

CFE 55 51 164 +

CFE 56 52 165 +

CFE 57 53 166 +

CFE 58 54 167 +

CFE 60 56 169 +

CFE 61 57 170 +

CFE 64 60 173 +

CFE 65 61 174 +

CFE 66 62 175 +

CFE. 67 63 176 +

CFE 69 65 178 ~,~ , +

CFE 70 66 179 +

CFE 73 69 182 +

CFE 75 71 ~ 184 -CFE 76 72 185 ' +

CFE 78 74 187 +

CFE 81 77 . 190 +

TABLE I
CFE Designation SEQ. ID NO. SEQ. POLARITY
(Nucleotide) ID
NO.
(Polypeptide) CFE 86 ~ 82 195 -CFE 87 ~ 83 196 -CFE 89 85 198 +

CFE 90 86 199 +

CFE 93 89 202 +

CFE 94 90 203 +

CFE 95 91 204 +

CFE 96 ~ 92 205 . +

CFE 99 95 208 +

CFE 100. . 96 209 CFE 102 98 211 +

CFE 103 . 99 212 -CFE 104 100 213 +

CFE 108 104 217 +

CFEl 10 106 219 -CFE 111 107 ' 220 . -CFE 114 110 . 223 CFE 117 ' 113 226 -TABLE II
CFE Designation SEQ. ID NO. SEQ. ID NO. FIGURE
(Nucleotide) (Polypeptide) 2CFE 3 2g 2CFE 13 3g 2CFE 15. 40 2CFE 21 q.4 2CFE 26 ' 47 2CFE'29 50 2CFE 31 . 52 2CFE 36 . 57 _ 2CFE 38 ' ~ 59 CFE.DesignationSEQ. ID NO. SEQ. ID NO. FIGURE
(Nucleotide) (Polypeptide) ~

2CFE 42 ' 63 2CFE 44 . . 65 2CFE 72 . 92 CFE DesignationSEQ. ID NO. SEQ. ID NO. FIGURE
(Nucleotide) (Polypeptide) 2CFE 81 9g 2CFE ~83 100 2CFE 86 . 103 2CFE 105 ~ 119 2CFE 106 . 120 2CFE 107 ~ 121 2CFE 112 ~ 125 2CFE 115. 128 2CFE 116 ' 129 a) Variant ceg Nucleotide Sequences The present invention also provides nucleic acid molecules having a nucleotide sequence substantially identical or similar to the ceg sequences (SEQ ID NOS: 1-113, 227-331) disclosed herein.
The present invention provides nucleotide sequences which are similar to SEQ
ID
NOS:1-113 andlor SEQ ID NOS:227-331. , The present invention provides nucleotide sequences which vary from SEQ ID NOS:1-113 or 227-331 by a range of about 1%
to about 70%.
The present invention encompasses variations in polynucleotide sequences resulting from mutations and/or from transfer of genetic material from one cell to another (e.g., horizontal gene transfer or horizontal gene exchange).
The present invention also provides for variants of the polynucleotide ceg sequences disclosed herein, including variants isolated from naturally-occurring sources, those generated by recombinant DNA technology or other in vitro synthesis methodologies (e.g., PCR). The variant polynucleotide sequences of the invention encode polypeptides that exhibit the biological activity of naturally-occurring CEG polypeptides, such as activity required for bacterial cell viability.
In general, for example, a variant of ceg polynucleotide sequences may encode a polypeptide that differs by one or more amino acid substitutions. The variant may have conservative changes, wherein a substituted amino acid has similar structural or chemical properties, eg, replacement of leucine with isoleucine.
A polynucleotide sequence can encode conservative amino acid substitutions without altering either the conformation or the 'function of the polypeptide. Such changes include substituting any of isoleucine (I), valine (V), and leucine (L) for any other of these hydrophobic amino acids; aspartic acid (D) for glutamic acid (E) and vice versa;
glutamine (Q) for asparagine (N) and vice versa; and serine (S) for threonine (T) and vice versa. Other substitutions can also be considered conservative, depending on the environment of the particular amino acid and its role in the three-dimensional structure of the protein. For example, glycine (G) and alanine (A) can frequently be interchangeable, as can alanine (A) and valine (V). Methionine (M), which is relatively hydrophobic, can .
frequently be interchanged with leucine and isoleucine, and sometimes with valine.
Lysine (K) and arginine (R) are frequently interchangeable in locations in which the significant feature of the amino acid residue is its charge and the differing pK's of these two amino acid residues are not significant. Still other changes can be considered "conservative" in particular environments.
A variant may also have nonconservative changes, eg, replacement of a glycine with a tryptophan. Other variations may also include amino acid deletions or insertions, or both.
Guidance in determining which and how many amino acid residues may be substituted, inserted or deleted without abolishing biological or immunological activity may be found using computer programs well known in the art, for example, DNASTAR software.
Another type of ceg sequence variant includes naturally-occurring allelic variants of ceg which share significant similarity (e.g., between about .30- 99%) to the disclosed CEG
polypeptide sequence. Allelic variants of the ceg sequences can encode conservative or non-conservative amino acid substitutions of the CEG polypeptide sequence herein described.
An example of. allelic variants of ceg are mutant alleles of ceg polynucleoticle sequences that encode a polypeptide having one or more changes in the polypeptide sequence, such as amino acid substitutions, deletions, insertions, frame shifts, or truncations.
The mutant alleles of ceg may or may not encode . a CEG polypeptide having the same biological functions as wild-type CEG proteins.
3.0 Variations in the bacterial genomic sequences can also arise from transfer of genetic material to another bacterial cell. The transfer of gene sequences can occur intraspecies or interspecies. Gene transfer can occur between bacterial cells which are members of the same or different populations. A population includes, but is not limited to, a serotype isolate, a clinical isolate, a naturally-occurring isolate, a strain, and a species. The transfer of genetic material can occur between cells within a population; for example transfer between serotype A to serotype A, or between S. pneumoniae and S.
pneumoniae. The transfer of genetic material can occur between cells of different populations; for example, between serotype A to serotype B or S pneumoniae and S.
mutans.
Gene transfer can give rise to mutant or polymorphic variant genes sequences.
In rare cases, gene transfer introduces new gene sequences that confer a new phenotype, such as antibiotic resistance. The transfer of genetic material includes transfer of large regions of genomic sequences which include partial gene sequences, whole single gene sequences, or multiple gene sequences. This mode of transfer can give rise to replacement of native whole gene sequences or introduction of new sequences in the recipient cell.
This mode of transfer gives rise to mosaic gene sequences in the recipient cell.
The variation of genomic sequences resulting from gene transfer can be examined using molecular techniques, including: multilocus enzyme electrophoresis (Selander.
R. K., et al., 1986 Appl. Ehvi~on. Mic~obiol. 51:837-884); and restriction endonuclease cleavage electrophoretic profiling (Coffey, T. J., et al., 1991 Mol. Mic~obio. 5:2255-2260); pulse-field gel electrophoresis fingerprinting (Bygraves, J. A. and Maiden, M. C. J.
1992 J.
Gen. Mic~obiol. 138:523-531); and ribotyping (Stull, T. L., et al., 1988 J.
Infect. Dis.
157:280-286). The degree of variation can vary greatly, and ranges from little or no variation as exemplified by gene sequences of E coli (Caugant, d. A.,, et al., Genetics 98:467-490; Whittam, T. S., et al., 1'983 MoL Biol. Evol. 1:67-83;
Souza, V., et al., 1992 P~oc. Natl. Acad. Sci. USA 89:8389-8393) and Salmonella (Selander, R. K., et al., 1990 Infect. Immun. 58:2262-2275; Selander, R.K. and Smith, N. H. 1990 Rev. Med.
Microbiol. 1:219-228; Smith, J. M., et al., 1993 P~oc. Natl. Acad. Sci. USA
90:4384-4388), to extensive gene transfer in Neisseria goho~rhoeae (Smith, J. M., et al., 1993 Proc. Natl. Acad. Sci. USA 90:4384-4388).
Gene transfer can be examined between various isolates of a particular microbial species which are antibiotic-sensitive or antibiotic-resistent (Coffey, T. J., et al., 1991 Molec.
Mic~obiol. 5:2255-2260). Molecular biology techniques can be utilized to study the degree of transfer between populations, such as, for example, the degree of gene transfer between serotypes, isolates, strains,-or species . The degree of transfer can be examined . by comparing, for example, the penicillin binding proteins and numerous different loci which encode metabolic enzymes or capsular biosynthesis enzymes. .
For example, intra-species, inter-serotype, gene transfer is possible (Coffey, T. J., et al., 1991 supra). Additionally, intraspecies gene transfer in S. pneumohiae (Coffey, T. J., et al., 1998 Mol. Mic~obiol. 27:73-83), Yib~io chole~ae (Bik, E. M., et al., 1995 EMBO J.
14:209-216), and Haemophilus influe~zae (Knoll, J. S. and Moxon, E. R. 1990 J.
Bacte~iol. 172: 1374-1379) are possible.
Interspecies gene transfer is also possible (Dowson, C. G., et al., 1989 Proc.
Natl. Acad.
Sci. USA 86:8842-8846; Laibl, G., et al., 1991 Mol. Mic~obiol. 5:1993-2002;
Bourgoin, F., et al., 1999 Gene 233:151-161).
Variant gene sequences arising from gene transfer can be continually generated in transformable bacteria (e.g., transformation competent), such as S.
pneumoniae. For example, the worldwide spread of varying degrees of antibiotic resistance has.
been documented and reviewed (Dowson, C. G., et al., 1994 Ti~euds Micr~obiol. 2:361-366;
Spratt, B. G. in Bacterial Cell Wall, eds Ghuysen J-M. and Hakenbeck, R. 1994 pp. 517-534; and reviewed in Maiden, M. C. J. 1998 Clinic. Infect. Dis. 27 (Supplement 1) S12-S20). For example, variant gene sequence arising from gene transfer can be tracked using a marker gene such as the gene which encodes the penicillin binding protein (.Barcus, V. A., et al., 1995 FEMSMic~obiol. Lett. 126:299-303). At the nucleotide level, gene sequences encoding the penicillin binding proteins in susceptible and resistant strains differ by about 14% to 23% (Hakenbeck, R. 1995 Biochem. Pharmacol.
50:1121-1127; Spratt, B. G. in Bacterial Cell Wall, eds Ghuysen J-M. and Hakenbeck, R.
1994-pp.
517-534; Spratt, B. G., et al., 1991 Neisseria mehiugitidis and Streptococcus pheumor~iae eds. Camisi, J., et al., pp. 73-83; CofFey, T. J., et al., 1995 Micro. Drug Resist. 1:29-34).
The ceg nucleotide sequences can be isolated from various species of Streptococcus including Streptococcus pneumohiae. Additionally, the ceg sequences can be isolated from other Steptococcal species, including S mutans, S pyoge~es, and S.
thermophila, The ceg polynucleotide sequences can also be isolated from strains of other bacterial genera including, but not limited to; Streptococcus, Escherichia, Bacillus, Pseudomohas, Yersinia, Salmonella, and Haemophilus.
The present invention additionally provides isolated codon-usage variants that.differ from the disclosed ceg nucleotide sequences, yet do not alter the predicted CEG
polypeptide sequence or function. The codon-usage variants may be generated by recombinant DNA
technology. Codons may be selected to optimize the level of production of the ceg transcript or CEG polypeptide. in a particular prokaryotic or eukaryotic expression host, in accordance with the frequency of codon utilized by the host cell.
Alternative reasons for altering the nucleotide sequence encoding a CEG polypeptide include the production of RNA transcripts having more desirable properties, such as an extended half life or increased stability. A multitude of variant ceg nucleotide sequences that encode the respective CEG polypeptide may be isolated, as a result of the degeneracy of the genetic code. Accordingly, the present invention contemplates selecting every possible triplet codon to generate every possible combination of nucleotide sequences that encode the disclosed CEG polypeptides. This particular embodiment provides isolated nucleotide sequences that vary from the sequences as described in SEQ ID NOs.: 1-113 or 227-331, such that each variant nucleotide sequence encodes a polypeptide having sequence identity with the amino acid sequences, as described in SEQ ID NOs.:l 14-226 or 332-436, respectively.

b) Complementary Sequences The present invention includes polynucleotide sequences that are complementary to the sequences disclosed herein. The term "complementary" as used herein refers to the capacity of purine and/or pyrimidine nucleotides to associate through hydrogen bonding to form double stranded nucleic acid molecules. The following base pairs are related by complementarity: guanine and cytosine; adenine and thymine; and adenine and uracil.
Complementary applies to all base pairs comprising at least two single-stranded nucleic acid molecules.
c) Sequences Capable of Hybridizing Another embodiment provides nucleic ' acid molecules that will hybridize to ceg . sequences under hybridization conditions. It is readily apparent to one skilled in the art that the stringency of the hybridization condition selected will depend upon the characteristics of the nucleic acid molecule to be hybridized, such as, the length, the degree of complementarity (e.g., exact or non-exact complementarity), the percent A/T
content, and the objective of the hybridization experiment.
The hybridization procedure may by performed in low stringency hybridization conditions. Low stringency hybridization conditions will permit hybridization between two nucleic acid molecules that differ from exact complementarity by about 25%
to 70%.
Hybridization under standard high stringency conditions will occur between two complementary nucleic acid molecules (e.g., 100% exact complementarity) or.
two complementary nucleic acid molecules that differ from exact complementarity by about 1 % to about 70%.
The high stringency hybridization conditions that disfavor non-homologous base pairing are well known in the art. Typically, high stringency hybridization conditions, includes but is not limited to, hybridizing at 50 °C to 65 °C in SX
~SSPE, and washing at 50 °C to 65 °C in O.SX SSPE. Typically, low stringency conditions, includes but is not limited to, hybridizing at 35 °C to 37 °C in SX SSPE and.40% to 45%
formamide and washing at 42 °C in 1-2X SSPE. The conditions arid formulas for high stringency hybridization methods are well known in the art and can be readily obtained in Molecular Clohihg; A
Laboratory Manual (2"d edition, Sambrook, Fritch, and Maniatis 1989, Cold Spring Harbor Press) or in Short Protocols ih Molecular Biology (Ausubel, F. M., et al., 1989, John Wiley & Sons).
d) Fragments of ceg Sequences The invention further provides nucleic acid molecules having fragments of the ceg sequences, such as a portion of the ceg sequence (e.g., SEQ ID NOS:1-113, 227-331) disclosed herein. The size of the fragment will be determined by its intended use. For example, the length of the fragment to be used as a nucleic acid probe or PCR
primer is chosen to obtain a relatively small number of false positives during probing or priming.
Alternatively, a fragment of the ceg sequence may be used to construct a recombinant fusion gene having a ceg sequence fused to a non-ceg sequence.
The nucleic acid molecules, fragments thereof, and probes and primers of the present invention are useful for a variety of molecular biology techniques including, for example, hybridization screens of libraries, or detection and quantification of mRNA
transcripts as a means for analysis of gene transcription and/or expression. Preferably, the probes and primers are DNA. A probe or primer length of- at least 15 base pairs is suggested by theoretical and practical considerations (Wallace, B. , and Miyada, . G. 1987 "Oligonucleotide Probes for the Screening of Recombinant DNA Libraries" in:
Methods in Enzymology, 152:432-442, Academic Press). Other lengths of fragments, probes, or primers are possible and routine to determine.
The probes and primers of this invention can be prepared by methods well known to those skilled in the art (Sambrook, et' al. supra). In a preferred embodiment the probes and primers are synthesized by chemical synthesis methods (ed: Gait, M. J.

Oligonucleotide Synthesis, IRL Press, Oxford, England).
One embodiment of the present invention provides nucleic acid primers that are complementary to ceg sequences, which allow the specific amplification of nucleic acid molecules of the invention or of any specific parts thereof. Another embodiment provides nucleic acid probes that are complementary for selectively or specifically hybridizing to the ceg sequences or to any part thereof.
e) Derivative Nucleic Acid Molecules ' _ The nucleic acid molecules of the invention include peptide nucleic acids (PNAs), or derivative molecules such as phosphorothioate, phosphotriester, phosphoramidate, and methylphosphonate, that specifically bind to single-stranded DNA or RNA in a base pair-dependent manner (Zamecnik, P. C., et al., 1978 P~oc. Natl. Acad. Sci.
75:280284;
Goodchild, P. C., et al., 1986 P~~oc. Natl. Acad. Sci. 83:4143-4146).
PNA molecules comprise a nucleic acid oligomer to which an amino acid residue, such as lysine, and an amino group have been added. These small molecules, also designated anti-gene agents, stop transcript elongation by binding to their complementary (template) strand of nucleic acid (Nielsen, P. E., et al., 1993 Anticahce~ Drug Des 8:53-63). For example, reviews of methods for synthesis of DNA, RNA, and their analogues can be found.in: Oligohucleotides and Analogues, eds. F. Eclcstein, 1991, IRL Press, New York;
Oligohucleotide Synthesis, ed. M. J. Gait, 1984, IRL Press, Oxford, England.
Additionally, methods for antisense RNA technology are described in U. S.
patents 5,194,428, and 5,110,802. A slcilled artisan can readily obtain these classes of nucleic acid molecules using the herein described ceg polynucleotide sequences, see for example Innovative ahd Perspectives i~ Solid Phase Synthesis (1992) Egholm, et al. pp 325-328 or U. S. Patent No. 5,539,082.

f7 RNA Molecules The present invention provides RNA molecules that encode the predicted ceg gene products. In particular, the RNA molecules of the invention may be isolated full-length or partial mRNA molecules or RNA oligomers that encode CEG gene products. The RNA molecules of the invention include the nucleotide sequences encoding all or portions of CEGs.
The RNA molecules of the invention also include antisense RNA molecules, peptide nucleic acids. (PNAs), or non-nucleic acid molecules such as phosphorothioate derivatives, that specifically bind to the. sense strand of DNA or RNA in a base pair-dependent manner. A skilled artisan can readily obtain these classes of nucleic acid molecules using the herein described ceg sequences.
g) Labeled Nucleic Acid Molecules The nucleic acid molecules having ceg sequences can be labeled with a detectable marker. Examples of a detectable marker include, but are not limited to, a radioisotope, a ' fluorescent compound, a bioluminescent compound, a chemiluminescent compound, a metal chelator or an enzyme. Technologies for generating labeled DNA and RNA
probes are well known in the art (See e.g. Sambrook et al., supra).
2.) RECOMBINANT NUCLEIC ACID MOLECULES
Also provided are recombinant nucleic .acid molecules, such as recombinant DNA
molecules (rDNAs) that comprise ceg sequences or fragments thereof. As used herein, a recombinant DNA molecule is a DNA molecule that has been subjected to molecular manipulation in vitro.
Methods for generating rDNA molecules are well known in the art, for example, see Sambrook et al., Molecular Cloning (199), supra.

a) Vectors The nucleic acid molecules of the invention may be recombinant molecules each comprising the sequence, or portions thereof, of a ceg sequence linked to a non-ceg sequence. For example, the ceg sequence may be fused operatively to a vector to generate a recombinant molecule. The term vector includes, but is not limited to, ' plasmids, cosmids, and phagemids. A preferred vector includes an autonomously replicating vector comprising a replicon that directs the replication of the rDNA within the appropriate host cell. The preferred vectors can also include an expression control element, such as a promoter sequence, which enables transcription of the inserted ceg sequences and can be used for regulating the expression (e.g., transcription and/or translation) of an operably linked ceg sequence in an appropriate host cell such as Esche~ichia coli. Expression control elements are lcnown in the art and include, but are not limited to, inducible promoters, constitutive promoters, secretion signals, enhancers, transcription terminators, and other transcriptional regulatory elements.
Other expression control elements that are involved in translation are known in the art, and include the Shine-Dalgarno sequence, and initiation and termination codons. The preferred vector also includes at least one selectable marker gene that encodes a gene product that confers drug resistance such as resistance to ampicillin or tetracyline. The vector also comprises multiple endonuclease restriction sites that enable convenient insertion of ,exogenous DNA sequences.
The preferred vectors for generating ceg transcripts and/or the encoded CEG
polypeptides are expression vectors which are compatible with prokaryotic host cells.
Prokaryotic cell expression vectors are well known in the art and are available from several commercial sources. For example, a pET vectors (e.g., pET-21, Novagen Corp.) may be used to express CEG polypeptides in bacterial host cells.

b) Recombinant Vectors for Integration The present invention provides recombinant vectors that may be used to integrate exogenously provided sequences into the genome of a host cell. The recombinant integration vectors of the present invention include a gene that encodes a selectable marker and ceg sequences; or fragments thereof The integration vectors are used to integrate the ceg sequence into a target gene sequence that resides within the bacterial host genome (e.g., endogenous sequence), thereby disrupting the function of the target gene sequence within the bacterial cells. These integration vectors may be used in a gene disruption assay to screen candidate ceg nucleotide sequences, in order to identify the candidate sequences that encode a gene product that is required for bacterial cell viability.
Accordingly, these recombinant integration vectors include candidate ceg sequences that ' will be screened to determine if the candidate ceg sequences encode a gene product that is required for cell viability. The candidate ceg sequence that is included as part of the recombinant integration vector is the "exogenous" ceg sequence that is employed as the "disrupting" sequence in a gene disruption assay. The ceg sequence that resides within the host genome is the "endogenous" or "target" ceg sequence.
The integration event rarely occurs, for example, by non-homologous recombination in which a recombinant vector, that includes the exogenous ceg sequence, inserts the exogenous ceg sequence into a random location within the host genome. In a more preferred embodiment, the integration event inserts the exogenous ceg sequence into a specific target site within the host genome. The targeted integration event can involve homologous recombination in which the integration vector, that includes the exogenous ceg sequence, inserts the exogenous ceg sequence into its homologous target ceg sequence that resides within the host's genome (e.g., the endogenous ceg sequence) (Figure 1). Further, the exogenous ceg sequence can be used as a disrupting sequence whereby the homologous recombination event integrates the exogenous ceg sequence into the endogenous target ceg sequence resulting in disruption of the function of the endogenous ceg sequence. For example, disrupting the function of the endogenous ceg sequence may result in the loss of bacterial cell viability.
An example of a recombinant vector that can be used as an integration vector in S
pneumoniae is the pEVP-3 vector (Jean-Pierre Claverys, et al. 1995 Gene 164:
123-128).
The pEVP-3 vector integrates an exogenous sequence by homologous recombination involving a Campbell-type event (S. Adhya and A. Campbell 1970 J. Mol. Biol.
50:481-490). The pEVP-3 vector includes a replicon that functions only in gram-negative bacteria, such as E. coli. Therefore, the pEVP-3 vector cannot replicate in S.
. pneumoniae. This vector also contains multiple cloning sites, and confers resistance to chloramphenicol in both a gram-negative and gram-positive bacteria, such as S
pneumohiae.
c) Fusion Gene Sequences A fusion ceg gene is another example of a recombinant molecule of the invention. A fusion gene includes a ceg sequence operatively fused (e.g., linked) to a non-ceg sequence such as, for example, a tag sequence to facilitate isolation and/or purification of the expressed CEG gene product (Kroll, D.J., et al., 1993 DNA Cell Biol 12:441-53).
Alternatively, a recombinant fusion molecule has a ceg sequence of the invention fused to a ceg sequence isolated from a different microbial source. For example, the disclosed ceg sequences isolated from S pneumoniae can be fused to a ceg sequence isolated from a different bacterial species.
3.) CEG PROTEINS AND POLYPEPTIDE MOLECULES
The invention additionally provides CEG proteins and peptide fragments thereof that are isolated or substantially purified. Embodiments of particular CEG amino acid sequences are disclosed in Tables I ,and II (SEQ ID NOS:114-226 and SEQ ID NOS:332-436, respectively).

The present invention also includes polypeptides having sequence variations from the predicted CEG polypeptide sequences disclosed herein, including mutant variants, conservative substitution variants, and similar CEG polypeptides from other prokaryotic organisms. For convenience, such proteins are referred to herein as "CEG
proteins", "CEG polypeptides", or "proteins of the invention".
As used herein, CEG protein refers to a polypeptide having amino acid sequence identity or similarity to any one of the predicted amino acid sequences, as provided in SEQ ID NO.:
114-226 or 332-436. The variant CEG polypeptides can be allelic forms of CEG, such as mutant forms of CEG polypeptides. The present invention also provides conservative substitution-mutants of the CEG proteins that maintain functional activity of wild-type CEG
(e.g., the CEG polypeptide is required for bacterial cell viability).
The CEG protein may be isolated from any source whether natural, synthetic, semi-synthetic, or recombinant. As used herein, "natural" refers to a polypeptide which is found in nature. Accordingly, the CEG proteins may be isolated from a prokaryotic organism, such as a bacterial strain including, but not limited to, Streptococcus, Esche~ichia, Bacillus, Pseudomonas, Ye~sinia, Salmonella, and Streptomyces.
The CEG
proteins of the invention, and fragments thereof, can also be generated by recombinant methods or chemical synthesis methods.
The CEG polypeptides of the invention are essential for the viability of a bacterial cell.
Further, the CEG polypeptides can exhibit at least any one of the following functions: a pantothenate kinase, a Holliday Junction branch migration protein, a single stranded DNA binding protein, a phosphoglucosamine mutase, an acetyltransferase, an uridylyltrarisferase, a malonyl CoenzymeA:ACP transcylase, a 3-oxoacyl-ACP
synthase II, a 3-oxoacyl-ACP reductase, a phosphomethylpyrimidine (HMP-P) kinase, a GTP
binding protein, a ATP binding protein, or a 4-aminoimidazole carboxylase.
Putative functions can include, but are not limited to, sugar transferase, techoic acid biosynthesis, ribosome recycling factor, response regulator, nicotinate phosphoribosyltransferase, nitropropane dioxygenase, (3R)-hydroxymyristol acyl carrier protein dehydrase, sugar dehydrogenase, murein biosynthesis, cobalimin biosynthesis, ABC transporter, tRNA
modification enzyme, arylsulfatase, 16S processing enzyme, tRNA methyl transferase, elongation factor P, signal recognition particle, 'protein export, undecaprenol kinase, SRP
docking domain, diacyl glycerol kinase, dihydopicilinate reductase, HU-DNA
binding protein, thiamine biosynthase, GreA transcription elongation factor, dTDP-L-rhamnose synthase, ATP-binding motif, ribose-5-p-3-epimerase-like activity, GTP
pyrophosphokinase, acetyl-CoA carboxylase, O-sialoglycoprotein endopeptidase, glucosamine-fructose-6-phosphase aminotransferase, Strpn adhesion-associated ABC-permease, GTP pyrophosphokinase ReIA, IMP dehydrogenase, DNA gyrase subunit B, acetyl-GoA carboxylase subunit AccD, phosphoglycerol kinase, acetyl-CoA
carboxylase carbonyl transferase,. phosphopanthetheine adenylyltransferase, oligopeptide transport permease subunit, translocation protein, perM permease, DNA pol III gamma and tau subunits, DNA pol III delta subunit, signal peptidase I, acetyl-coA
carboxylase biotin carboxyl carrier protein, protein chain release factor-1, replicative DNA
helicase, topoisomerase, pentapeptide-transferase, elongation factor G, spore coat polysaccharide biosynthesis protein C, protein 'release factor B, DNA polymerase III alpha subunit, phosphoprotein phosphatase, chaparonin, UDP-N-acetylmuramoylalanyl-D-glutamate-2, 6-diaminopimelate ligase, techuronic acid biosynthesis, UDP-glucose lipid carrier transferase, transcription termination factor, chromosome segregation factor, amino acid biosynthesis, HMG-CoA reductase, hypoxanthine-guanine phosphoribosyltransferase.
a) MODULATORS OF CEG POLYPEPTIDES
The invention provides compounds that modulate (e.g., activate or inhibit) the function of a CEG polypeptide. Such compounds can provide lead-compounds for developing drugs for diagnosing and/or treating conditions associated with bacterial infections. The modulator is a compound that may alter the function of the CEG polypeptide, such as activating or inhibiting the function of a CEG polypeptide. For example, the compound can act as agonist, antagonist, partial agonist, partial antagonist, cytotoxic agents, inhibitors' of cell proliferation, and cell proliferation-promoting agents.
The activity of the compound may be known, unknown or partially known.
Suitable ligands include, but are not limited'to, diazalactones, N protected amino acid, azabicyclodiene, and alkaloids.
An example of a diazalactone is:
O
N N02_ N

N02-, An example of a N protected amino acid is:
NH
O
O-An example of an azabicyclodiene is:
OH

Examples of alkaloids are:
F ~ F N\ 'N
~'N
~N I / N . N ,N
N CI / N
N N
CI
CI
O
N i ~N
N ~ \ I NONI
.N, N ~ NJ ~N\
B) METHODS FOR MAKING THE CEG PROTEINS AND POLYPEPTIDES
Recombinant methods are preferred if a high yield is desired.
Recombinant.methods involve expressing the cloned gene in a suitable host cell. For example, a host cell is introduced with an expression vector having the CEG sequence, then the host cell is cultured under conditions that permit in vivo production of the CEG protein.
The recombinant vector can integrate the CEG sequence into the host genome.
Alternatively, the CEG sequence can be maintained extra-chromosomally, as part of an autonomously replicating vector.
1. HOST-VECTOR SYSTEMS
The invention further provides a host-vector system comprising the vector, plasmid, phagemid, or cosmid comprising a ceg nucleotide sequence, or a fragment thereof, introduced into a suitable host cell. The host-vector system can be used to produce the CEG polypeptides encoded by the ceg nucleotide sequences. The host cell can be prokaryotic ~or eukaryotic. Examples of suitable prokaryotic host cells include bacteria strains from genera such as Esche~ichia, Bacillus, Pseudomovcas, Streptococcus, and St~eptomyces. Examples of suitable eukaryotic host cells include a yeast cell, a plant cell, or an animal cell, such as a mammalian cell. A preferred embodiment provides a host-vector system comprising the pET21 vector having a ceg sequence introduced into an E.
coli ~,DE3 lysogen which is useful, for example for the production of the CEG
protein, herein designated CFE polypeptides and CFE proteins.
Introduction of the rDNA molecules of the present invention into an appropriate cell host is accomplished by well known methods that typically depend on the type of vector used and host system employed. For example, transformation of prokaryotic host cells by electroporation and salt treatment methods are typically employed, see for example, Cohen et al., 1972 P~oc Acad Sci USA 69:2110; Maniatis, T., et al., 1989 Molecular Cloning, A
Labo~~ato~y Mahual, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY.
Transformation of vertebrate cells with vectors containing rDNAs, electroporatibn, cationic lipid or salt treatment methods are typically employed, see, for example, Graham et al., 1973 Virol 52:456; Wigler et al., 1979 P~~oc Natl Acad Sci USA 76:1373-76.
Successfully transformed cells, i.e., cells that contain a rDNA molecule of the present invention, can be identified by well known techniques. For example, cells resulting from the introduction of a rDNA of the present invention can be selected and cloned to produce single colonies. Cells from those colonies can be harvested, lysed and their DNA content examined for the presence of the rDNA using a method such as that described by Southern, JMol Biol (1975) 98:503, or Berent et al., Biotech (1985) 3:208, or the proteins produced from the cell assayed via a biochemical assay or immunological method.
Procaxyotes are generally used as host cells for cloning and producing the products of exogenous DNA sequences. For example, the Esche~ichia coli K12 BL21 (7~DE3) (Novagen) is particularly useful for expression of foreign proteins. Other strains of E.
coli, and bacilli such as Bacillus subtilis, Enterobacteriaceae such as Salmonella typhimur~ium or Se~r~atia ma~cescans, various Pseudomonas, Streptococcus, and Streptomyces species may also be employed as host cells in cloning and expressing the recombinant proteins of this invention.
In general terms, the production of recombinant CEG proteins may involve using a host/vector system, or other methods may be used. The host/vector system may employ the following steps.
A nucleic acid molecule is obtained that encodes a CEG protein or a fragment thereof, such as any one of the polynucleotides disclosed in SEQ ID NOs.: 1-113 or 227-331.
The CEG-encoding nucleic acid molecule is preferably inserted into an expression vector in operable linkage with suitable expression control sequences, to generate an expression vector including the CEG-encoding sequence. The expression vector is introduced into a suitable host, by standard transformation methods, and the resulting transformed host is cultured under conditions that allow the production of the CEG protein. For example, if expression of the CEG gene is under the control of an inducible promoter, then 'suitable growth conditions would include the appropriate inducer. The CEG protein (e.g., designated a CFE polypeptide or protein), so produced, is isolated from the growth medium or directly from the cells; recovery and purification of the protein may not be necessary in some instances where some impurities may be tolerated. A skilled artisan can readily adapt an appropriate host/expression system known in the art for use with CEG-encoding sequences to produce a CEG protein.(Cohen, et al., supra; Maniatis et al., supra).
Host cells harboring the nucleic acids disclosed herein are also provided by the present invention. A preferred host is E. coli strain BL21(~,DE3) transfected or transformed with a vector comprising a nucleic acid of the present invention. The invention also provides a host cell capable of expressing the ceg sequences described herein. The preferred host cell is any strain of E. coli that can accommodate high level expression of an exogenously introduced gene.

The proteins of the present invention can also be made by chemical synthesis.
The principles of solid phase chemical synthesis of polypeptides axe well known in the art and may be found in general texts relating to this area (Dugas, H. and Penney, C.

Bioo~ganic Chemistry, pp 54-92, Springer-Verlag, New York). CEG polypeptides may be synthesized ~by solid-phase methodology utilizing an Applied Biosystems peptide synthesizer (Applied Biosystems, Foster City, Calif.) and synthesis cycles supplied by Applied Biosystems. Protected amino acids, such as t-butoxycarbonyl-protected amino acids, and other reagents are commercially available from many chemical supply houses.
The polypeptides of the invention exhibit properties of a CEG protein, such as, for example, the ability to elicit the generation of antibodies that specifically bind an epitope associated with CEG polypeptides. Accordingly, the CEG polypeptide, or any oligopeptide thereof, is capable of inducing a specific immune response in appropriate animals or cells and binding with specific antibodies.
C) ANTIBODIES THAT RECOGNIZE AND BIND THE PROTEINS AND
POLYPEPTIDES OF THE INVENTION
The invention fiarther provides antibodies (e.g., polyclonal, monoclonal, chimeric, humanized, and human antibodies) that bind a CEG polypeptide. The most preferred antibodies will selectively bind a CEG polypeptide and will not bind (or will bind weakly) a non-CEG polypeptide. Antibodies that are particularly contemplated include monoclonal and polyclonal antibodies, as well as fragments thereof (e.g., recombinant proteins) which include the.antigen binding domain andlor one or more complement determining regions of these antibodies. These antibodies can be from any source, for example, rabbit, sheep, rat, dog, cat, pig, horse, mouse, and human.
The invention encompasses antibody fragments that specifically recognize a CEG
polypeptide. As used herein, an antibody fragment is defined as at least a portion of the variable region of the immunoglobulin molecule that binds to its target, i.e., the antigen binding region. Some of the constant region of the irilmunoglobulin may be included.

As will be understood by those skilled in the art, the , regions or epitopes of a CEG
polypeptide to which an antibody is directed may vary with the intended application. For example, antibodies intended for use in an immunoassay for the detection of membrane-bound CEG proteins on viable bacterial cells should be directed to an accessible epitope on membrane-bound CEG proteins. Antibodies that recognize other epitopes may be useful for the identification of CEG protein within damaged or dying cells, for the detection of secreted CEG protein or fragments thereof.
Various methods for the preparation of antibodies are well known in the art.
For example, antibodies may be prepared by immunizing a suitable mammalian host using a CEG
protein, peptide, or fragment, in isolated or immunoconjugated form (Harlow, 1989 Antibodies, Cold Spring Harbor Press, NY). In addition, fusion~proteins comprising CEG
polypeptides may also be used, such as a CEG protein/GST-fusion protein. Cells expressing or overexpressing a CEG polypeptide may also be used for immunizations. Similarly, any cell engineered to express CEG protein may be used. This strategy may result in the production of monoclonal antibodies with enhanced capacities for recognizing endogenous CEG protein.
The present invention contemplates chimeric antibodies that comprise a human and non-human immunoglobin portion. The antigen combining region (vaxiable region) of a chimeric antibody can be derived from a prokaryotic source (e.g., bacteria) and the constant region of the chimeric antibody which confers biological effector function to the immunoglobulin can be derived from a eukaryotic source (e.g., human). The chimeric antibody should have the antigen binding specificity of the prokaryotic antibody molecule and the effector function conferred by the eukaxyotic antibody molecule.
In one example, the procedure used to produce chimeric antibodies can involve the following steps:
a) Identifying and cloning the correct immunoglobin gene segment encoding the w antigen binding portion of the antibody molecule. This gene segment is known as the VDJ, variable, diversity and joining regions. for heavy chains or VJ, variable, joining regions for light chains or simply as the V or variable region. This gene regions may be in either the cDNA or genomic form;
b) Cloning the gene segments encoding the constant region or desired part thereof;
c) Ligating the variable region with the constant region so that the complete chimeric antibody is encoded in a form that can be transcribed and translated;
d) Ligating this construct into a vector containing a selectable marker and gene control regions such as promoters, enhancers and poly(A) addition signals;
e) Amplifying this construct in bacteria;
f) Introducing this DNA into eulcaryotic cells (transfection) most often mammalian lymphocytes;
g) Selecting for cells expressing the selectable marker;
h) Screening for cells expressing the desired chimeric antibody; and k) Testing the antibody for appropriate binding specificity and effector functions.
Chimeric antibodies of several distinct antigen binding specificities have been produced by protocols well known in the art, including anti-TNP antibodies (Boulianne et al., 1984 Nature 312:643); and anti-tumor antigen antibodies (Sahagan et al., 1986 J.
Immuuol.
137:1066). Likewise, several different effector functions have been achieved by linking new sequences to those encoding the antigen binding region. Examples of these include enzymes (Neuberger et al., 1984 Nature 312:604); immunoglobulin constant regions from another species and constant regions of ~anothex immunoglobulin chain (Sharon et al., 1984 Natu~~e 309:364; Tan et al., 1985 J. Immuuol. 135:3565-3567).
Additionally, ' procedures for modifying antibody molecules and for producing chimeric antibody molecules using homologous recombination to target gene modification have been described (Fell et al., 1989 P~oc. Natl. Acad. Sci. USA 86:8507-8511).
The predicted amino acid sequence of a CEG protein may be used to select specific regions of the CEG protein for generating antibodies. For example, hydrophobicity and hydrophilicity analyses of a CEG polypeptide may be used to identify hydrophobic and hydrophilic regions in the CEG protein. Regions of the CEG protein that show immunogenic structure, as well as other regions and domains, can readily be identified using various other methods . known in the art, such as Chou-Fasman, Gamier-Robson , Kyte-Doolittle, Eisenberg, Karplus-Schult or Jameson-Wolf analysis. Fragments that include the immunogenic regions are particularly suited for generating specific classes of antibodies.
Methods for preparing a protein for use as an immunogen and for preparing immunogenic conjugates of a protein with a carrier such as BSA, KLH, or other carrier proteins are well known in the art. In some circumstances, direct conjugation using, for example, carbodiimide reagents may be used; in other instances linking reagents such as those supplied by Pierce Chemical Co., Rockford, IL, may be effective.
Administration of a CEG
immunogen is conducted generally by injection over a suitable time period and with use of a suitable adjuvant, as is generally understood in the art. During the immunization schedule, titers of antibodies can be taken to determine adequacy of polyclonal antibody formation.
While the polyclonal antisera produced in this way may be satisfactory for some applications, for pharmaceutical compositions, monoclonal antibody preparations are preferred. .Immortalized cell lines which secrete a desired monoclonal antibody may be prepared using the standard method of Kohler and Milstein (Nature 256: 495-497) or other techniques as described in Monoclonal Antibodies; A Manual of Techniques, CRC
press, Inc., Boca Raton, Fla. ' (1987) ed. Zola. The immortalized cell lines secreting the desired antibodies are screened by immunoassay in which the antigen is the CEG
polypeptide having binding activity, or a fragment thereof When the appropriate immortalized cell culture secreting the desired antibody is identified, the cells can be cultured either in vitro or by production in ascites fluid.
The desired monoclonal antibodies axe then recovered from the culture supernatant or from the ascites supernatant. Fragments of the monoclonal antibodies of the invention or the polyclonal antisera (e.g., Fab, F(ab')2, Fv fragments, fusion proteins) which contain the immunologically significant portion (i.e., a portion that recognizes and binds a CEG protein) can be used as antagonists, as well as the intact antibodies. Humanized antibodies directed against a CEG polypeptide are also useful. The advantage of using humanized antibodies is that they are less immunogenic in humans. As used herein, a humanized antibody is an immunoglobulin molecule which is capable of binding to a CEG polypeptide and which comprises a FR region having substantially the amino acid sequence of a human immunoglobulin and a CDR having substantially the amino acid sequence of non-human immunoglobulin or a sequence engineered to bind a CEG protein. Methods for humanizing marine and other non-human antibodies by substituting one or more of the non-human antibody CDRs for corresponding human antibody sequences are well known (Jones et al., 1986 Nature 321: 522-525; Riechmnan et al., 1988 Nature 332: 323-327;
Verhoeyen et al., 1988 Science 239: 1534-1536; Carter et al., 1993 Proc. Natl. Acad. Sci. USA
89: 4285;
and Sims et al., 1993 J. Immur~ol. 1'51: 2296).
Use of immunologically reactive fragments, such as the Fab, Fah', or F(ab')2 fragments is often preferable, especially in a therapeutic context, as these fragments are generally less immunogenic than the whole immunoglobulin. Further, bi-specific antibodies specific for two or more epitopes may be generated using methods generally known in the art. Further, antibody effector functions may be modified so as to enhance the therapeutic effect of the antibodies of the invention. For example, cysteine residues may be engineered into the Fc region, permitting the formation of interchain disulfide bonds and the generation of homodimers which may have enhanced capacities for internalization, ADCC and/or ' complement-mediated cell killing (Caron et al., 1992 J. Exp. Med. 176: 1191-1195;
Shopes, 1992 J. Immur~ol. 148: 2918-2922). Homodimeric antibodies may also be generated by cross-linking techniques known in the art (Wolff et al., Cancer Res. 53: 2560-2565). The invention also provides pharmaceutical compositions having the monoclonal antibodies or anti-idiotypic monoclonal antibodies of the invention.
The antibbdies or fragments may also be produced, using current technology, by recombinant means. Regions that bind specifically to the desired regions of the CEG
protein can also- be produced in the context of chimeric or CDR grafted antibodies of multiple species origin. The invention includes an antibody, e.g., a monoclonal antibody which competitively inhibits the. immunospecific binding of any of the monoclonal antibodies of the invention to a CEG protein.

Alternatively, methods for producing fully human monoclonal antibodies, include phage display and transgenic methods, are known and may be used for the generation of human monoclonal antibodies (reviewed in: Vaughan et al., 1998 Nature Biotechnology 16: 535-539). For example, fully human monoclonal antibodies may be generated using cloning technologies employing large human Ig gene combinatorial libraries (i.e., phage display) (Gxiffiths and Hoogenboom, "Building an in vitro immune system: human antibodies from phage display libraries"; in: Protein Engineering of Antibody Molecules for Prophylactic and Therapeutic Applications in Man, Clarlc, M. (Ed.), Nottingham Academic, pp (1993); Burton and Barbas, "Human Antibodies from combinatorial libraries"
Id., pp 65-' 82). Fully human monoclonal antibodies may also be produced using transgenic mice engineered to contain human immunoglobulin gene loci as described in PCT
Patent Application W098124893, Jakobovits et al., published December 3, 1997 (see also, Jakobovits, 1998 Exp. Opin. Invest. Drugs 7: 607-614). This method avoids the in viti o manipulation required with phage display technology and efficiently produces high affinity, authentic human antibodies.
The antibody or fragment thereof of the invention may be labeled with a detectable marker or conjugated to a second molecule, such as a therapeutic agent (e.g., a cytotoxic agent) thereby resulting in an immunoconjugate. For example, the therapeutic agent includes, but is not.limited to, an anti-tumor drug, a toxin, a radioactive agent, a cytokine, a second antibody or an enzyme. Further, the invention provides an embodiment wherein the antibody of the invention is linked to an enzyme that converts a prodrug into a cytotoxic drug.
Examples of cytotoxic agents include, but are not limited to ricin, ricin A-chain, doxorubicin, daunorubicin, taxol, ethiduim bromides mitomycin, etoposide, tenoposide, viricristine, vinblastine, colchicine, dihydroxy anthracin dione, actinomycin D, diphteria toxin, Pseudomonas exotoxin (PE) A, PE40, abrin, arbrin A chain, modeccin A
chain, alpha-sarcin, gelonin, mitogellin, retstrictocin, phenomycin, enomycin, curicin, crotin, calicheamicin, sapaonaria officinalis inhibitor, and glucocorticoid and other chemotherapeutic agents, as well as radioisotopes such as 212Bi, i3ih l3iln, 9oY, and ls6Re.

Suitable detectable markers for diagnostic used include, but are not limited to, a radioisotope, a fluorescent compound, a bioluminescent compound, chemiluminescent compound, a metal chelator or an enzyme. . Antibodies may also be conjugated to an anti-s cancer pro-drug activating enzyme capable of converting the pro-drug to its active form.
See, for example, U.S. Patent Nos. 4,952,394 and 5,716,990.
Additionally, a recombinant protein of the invention comprising the antigen-binding region of any of the monoclonal antibodies of the invention can be made. In such a situation, the antigen-binding region of the recombinant protein is joined to at least a functionally active portion of a second protein having therapeutic activity.
The second protein can include, but is not limited to, an enzyme, lymphokine, oncostatin or toxin.
Suitable toxins include those described above.
Techniques for conjugating or joining therapeutic agents to antibodies are well known (Arnon et al., "Monoclonal Antibodies For Immunotargeting Of Drugs In Cancer Therapy", in: Monoclonal Antibodies Avid Cancer Therapy, Reisfeld et al. (eds.), pp. 243-56, Alan R.
Liss, Inc. 1985; Hellstrom et al., "Antibodies For Drug Delivery", in:
Coht~olled Drug Delivery (2nd Ed.), Robinson et al. (eds.), pp. 623-53, Marcel Dekker, Inc.
1987; Thorpe, "Antibody Carriers Of Cytotoxic Agents In Cancer Therapy: A Review", in:
Monoclonal Antibodies '84: Biological Aid Clinical Applications, Pinchera et al. (eds.), pp. 475-506 (1985); and Thorpe et al., "The Preparation And Cytotoxic Properties Of Antibody-Toxin Conjugates", in: Immu~ol. Rev., 62:119-58 (1982)). 'Techniques for joining detectable markers to antibodies are also known.
D) PHARMACEUTICAL COMPOSITIONS OF THE INVENTION
The invention includes pharmaceutical compositions for use in the treatment of microbial infections comprising a pharmaceutically effective amount of an anti-CEG
antibody or a CEG polypeptide.

In one embodiment, the pharmaceutical compositions may comprise a CEG
antibody, either unmodified, conjugated to a therapeutic agent (e.g., drug, toxin, enzyme or second antibody) or in a recombinant form (e.g., chimeric or bispecific). The compositions may additionally include other antibodies or conjugates (e.g., an antibody cocktail).
The pharmaceutical compositions also preferably include suitable carriers and adjuvants which include any material which when combined with the molecule of the invention (e.g., an anti-CEG antibody or a CEG protein) retains the molecule's activity and is non-reactive with the subject's immune systems. Examples of suitable carriers and adjuvants include, but are not limited to, human serum albumin, ion exchangers, alumina, lecithin, buffer substances such as phosphates, glycine, sorbic acid, potassium sorbate, and salts or electrolytes such as protamine sulfate. Other examples include any of the standard pharrriaceutical catTiers such as a phosphate buffered saline solution, water, emulsions such as oil/water emulsion, and various types of wetting agents. Other carriers may also include sterile solutions, tablets including coated tablets and. capsules.
Typically such carriers contain excipients such as starch, milk, sugar, certain types of clay, gelatin, steaxic acid or salts thereof, magnesium or calcium stearate, talc, vegetable fats or oils, gums, glycols, or other known excipients. Such carriers may also include flavor and color additives or other ingredients. Compositions comprising such carriers are ~ formulated by well known conventional methods. Such compositions may also be formulated within various lipid compositions, such as, for example, liposomes as well as in various polymeric compositions, such as polymer microspheres.
The pharmaceutical compositions of the invention can be administered using conventional modes of administration including, but not limited , to, intravenous, intraperitoneal, oral, intralymphatic or administration directly into the tumor.
Intravenous administration is preferred.
The pharmaceutical compositions of the .invention may be in a variety of dosage forms which include, but are not limited to, liquid solutions or suspensions, tablets, pills, powders, suppositories, polymeric microcapsules or microvesicles, liposomes, and injectable or infusible solutions. The preferred form depends upon the mode of administration and the therapeutic application.
The CEG polypeptides and proteins of this invention are found in common pathogenic bacterial species such as Streptococcus pneumoniae. This organism causes upper respiratory tract infections. Thus, the peptides and proteins of this invention can be used as immunogens in subunit vaccines for vaccination against a pathogenic bacteria such as Streptococcus pneumoniae. Additionally, the ceg sequences of the invention can be used as DNA vaccines (U.S. Patent No. 5,736,524 and U.S. Patent No. 5,989,553).
..
The polypeptides and proteins of this invention can be formulated , as univalent and multivalent vaccines. The protein can be mixed, conjugated or fused with other antigens, including B or T cell epitopes of other antigens. -Further, when a haptenic peptide of the proteins of the invention is used, (i.e., a peptide which reacts with cognate antibodies, but cannot itself elicit an immune response), it can be conjugated to an immunogenic carrier molecule. Conjugation to an immunogenic carrier can render the oligopeptide immunogenic. Examples of carrier molecules are tetanus toxin or toxoid, diphtheria toxin or toxoid and any mutant forms of these proteins 20. such as CRM₁₉₇. Others include exotoxin A of Pseudomohas, the heat labile toxin of E. coli and rotaviral particles (including rotavirus and VP6 particles).
Alternatively, a fragment or epitope of the carrier protein or other immunogenic protein can be used. For example, the happen can be coupled to a T cell epitope of a bacterial toxin.
In formulating the vaccine compositions with the CEG polypeptides or proteins of the invention, alone or in the various combinations described, the immunogen is adjusted to an appropriate concentration and formulated with any suitable vaccine adjuvant. Suitable adjuvants include, but are not limited to: surface active substances, e.g., hexadecylamine, octadecylamine, octadecyl amino acid esters, lysolecithin, dimethyl-dioctadecylammonium bromide), methoxyhexadecylgylcerol, and pluronic polyols;
polyamines, e.g., pyran, dextransulfate, poly. IC, carbopol; peptides, e.g., muramyl dipeptide, dimethylglycine, tuftsin; oil emulsions; and mineral gels, e.g., aluminum hydroxide, aluminum phosphate, etc. and immune stimulating complexes. The immunogen may also be incorporated into liposomes, or conjugated to polysaccharides and/or other polymers.
The vaccines can be administered to a human or animal in a variety of ways.
These include intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, oral and intranasal ~ rou'tes of administration. Further, the vaccines can be live or inactivated vaccines.
The most effective mode of administration and dosage regimen for the compositions of this invention depends upon the severity and course of the disease, the patient's health and response to treatment and the judgment of the treating physician.
Accordingly, the dosages of the compositions should be titrated to the individual patient.
E) USES OF THE MOLECULES OF THE INVENTION
1) MOLECULAR WEIGHT MARKERS
The nucleic acid molecules of the invention and their encoded proteins may be employed as molecular weight marlcers. For example, the molecular weight of each of the nucleic acid molecules having ceg sequences and their predicted polypeptides can be determined and can be used to compare against other gene sequences and proteins whose molecular weights are unknown.
2) DIAGNOSTICS
The nucleic acid molecules of the invention may be employed in diagnostic eriibodiments.~ For example, the presence of nucleotide sequences which are identical or similar to the ceg sequences of the invention may be detected within a biological sample.

The biological sample may include blood, serum or a swab from nose, ear or throat, may be determined by means of a nucleic acid detection assay.
Nucleic acid probes or primers having sequences complementary to ceg sequences may be used in a hybridization assay to detect the presence of the sequences which are identical or similar to the ceg sequences of the invention in the biological samples.
Typically, nucleic acids molecules obtained from a suitable biological sample are hybridized with labeled probes or primers. The resulting hybridized molecules are detected and resolved by methods well known in the art , such as Northern or Southern blotting, micro-array technology, or amplifying with PCR technology. Other hybridization techniques and systems are known that can be used in connection with the detection aspects of the invention, including diagnostic assays such as those described in Falkow et al., U.S. Pat. No. 4,358,535.
. Examples of the PCR technology are disclosed in U.S. Patent Nos. 4,683,202 and 4,965,188 (incorporated herein by reference). Generally, nucleic acid molecules are obtained from a suitable biological source and contacted with two primers corresponding to the ceg sequences disclosed herein, under conditions which allow for hybridization and polymerization to occur. A pair of probes, one corresponding to the 5' flanking region and the other corresponding to the 3' flanking region would be sufficient to detect the nucleic acid molecules of the invention in a biological sample and may be used to indicate the amount of bacteria present.
Alternative methods of detecting nucleic acid molecules include, for example, in situ hybridization techniques, where a ceg probe is used to detect homologous sequences within one or more cells, such as cells within a clinical sample or even cells grown in tissue culture. As is well known in the art, the cells are prepared for hybridization by fixation, e.g. chemical fixation, and placed in conditions that allow for the hybridization of a detectable probe with nucleic acids located within the fixed cell.

The amount of ceg sequences present in a biological sample can be quantified and compared to the levels in a normal or "healthy" sample. For example, ceg sequences present in either increased or decreased levels, compared to the levels found in the control sample may indicate the presence of bacteria. This information is useful for ' diagnosis of a bacterial infection that requires treatment with an antibacterial agent.
Alternatively, the amount of CEG polypeptides present in a biological sample may be determined by means of an immunoassay. For example, labeled antibodies reactive against CEG polypeptides may be used in an immuno-reactive assay to detect the presence of CEG polypeptides in the biological samples.
3) SCREENING CANDIDATE CEG SEQUENCES
a) Gene Disruption Assay The ceg nucleotide sequences of the invention can be used to identify nucleotide sequences which are identical or similar to the ceg sequences that are required for bacterial cell viability. For example, the ceg sequences can be used in a bacterial gene disruption assay to screen candidate nucleotide sequences to identify sequences required for bacterial cell viability.
The disruption assay can involve: introducing into a host cell a recombinant vector that is capable of integration into the host genome, where the recombinant vector, includes a candidate sequence that putatively encodes a cell-viability gene product (e.g., the exogenous ceg sequence); the vector integrates the candidate sequence into a target sequence within the host's genome (e.g., the endogenous ceg sequence); and the host cell, so introduced, is screened for viability. The recombinant vector preferably includes a selectable marker so that the introduced host cell can be screened for viability in the presence of a selectable agent.

For example, Figure 1 shows a schematic representation of a gene disruption assay, within a bacterial host cell. In Figure .1A, the recombinant vector, pEVP3, includes the CAT gene (e.g., the selectable marker chloramphenicol acetyl transferase) and an internal region of the ceg disrupting sequence; the internal region excludes the 5' and 3' ends of the ceg sequence. The "X" in Figure 1 indicates the recombinant pEVP3 vector undergoing homologous recombination with the target sequence (e.g., within the host genome). In Figure 1B, the resolved pEVP3 vector that is integrated into the host genome, is shown.
Left to right are the following elements: the native promoter of the target gene; a 5' partial copy of the target gene; the body of the integrated pEVP3 vector including the disrupting gene and CAT; and, a 3' partial copy of the target gene. Thus, integration of the pEVP3 vector via homologous recombination results in two partial gene duplications flanking the integrated vector. If the target gene is not essential for survival, it is possible to recover chloramphenicol-resistant colonies of S. pheumoniae. Failure to recover chloramphenicol resistant colonies, in the presence of the proper controls as described below, indicates that the target gene may be essential for cell viability.
More particularly, the gene disruption assay for screening candidate ceg sequences can involve the following steps. The recombinant pEVP-3 . vector encoding CAT
resistance and having a fragment of a candidate ceg sequence, can be introduced into transformation-competent S. pheumoniae cells by methods that are well-known in the art (Lee, M.S., et al., 1998 Appl. Euvirot~. Microbiol. 64:4796-4802). The preferred size of the ceg fragment can be between about 200 to about 500 by in length. It is advantageous that the candidate ceg sequence does not include the 5' and 3' ends that encode the N-and C-terminal ends of the CEG polypeptide. This insures that the inserted ceg fragment and the disrupted endogenous ceg gene sequence are not capable of expression of a full-length, functional ceg gene product. The transformation-competent cells can be obtained by performing the transformation step in the presence of a heptadecapeptide that induces competence for transformation of S pheumohiae (Havaxstein, L. S., et al., 1995 P~oc.
Nat'l. Acad. Sci. 92:11140-11144), such as the CSP-1 -peptide. The CSP-1 can be naturally-derived or synthetic. Additionally, the transformation step can.be optimized by performing the transformation when the cells have reached a density which is optimal for transformation (e.g.,. 3 X 10' cells per ml.) (Havaxstein, L. S. et al.
supra). The recombinant vector can be introduced into the competent pneumococci and may undergo homologous recombination, whereby the candidate ceg fragment recombines with the corresponding endogenous ceg sequence, resulting in targeted integration of the vector into the pneumococcal genome and disruption of the endogenous ceg.
The transformed cells can be plated on or cultured in chloramphenicol-containing growth medium. The cells can be cultured under standard conditions, such as 37° C in 5% COz, for approximately 40 to 48 hours, for the purpose of selecting cells that carry the integrated vector.
Additionally, control samples can be run in parallel with the gene disruption assay, in order to determine whether the gene disruption procedure is working properly.
For example, the control samples can be used to calibrate the gene disruption experiment so that disruption of a known non-essential bacterial gene results in an approximate number of colonies per plate. Similarly, the disruption of a known essential gene can be calibrated to yield only zero or one colony per plate. The appearance of one colony is due to the rare illegitimate recombination into a non-homologous sequence. In particular, a knov~m non-essential gene such as the lytA gene (Tomasz, A., et al., 1988 J.
Bacte~iol.
170:5931-5934) can be used so that between about 70 to 100 chloramphenicol-resistant colonies will grow per plate. Similarly, the ftsZ gene (Lutkenhaus, J. F., et al., 1980 J.
Bacte~iol. 143:1281-1288), a known essential gene, can be used to yield zero or, rarely, one colony per plate. As is well known in the art, specific parameters that are involved in any given gene disruption assay can be adjusted to calibrate the desired number of plated cells in the control samples. Experimental parameters that can be adjusted include, but are not limited to, the E. coli strain used to propagate the vector/insert, the fragment length of the sequence to be integrated, the amount of recombinant integration vector used to transform the cells, use of transformation-competent cells, and plating density of the transformed cells.

The transformed cells carrying the recombinant integration vector that disrupts expression of an endogenous essential gene (e.g., the target ceg gene) can be identified, based on a selectable phenotype such as non-viability. For example, the cells that carry a disrupted non-essential gene will be viable and, due to the integration of pEVP3, will grow on chloramphenicol-containing medium. In contrast, cells that carry a disrupted essential gene will not grow (e.g., non-viable) on the chloramphenicol-containing medium. ~ Thus, the transformed cells that do not grow under these selective conditions carry an endogenous gene sequence that is essential for cell viability which has been disrupted by an exogenous candidate fragment, thereby identifying a ceg sequence. Steps one through three may be repeated in order to confirm that the ceg sequences, so identified, are essential for cell viability.
b) Autolysin Assay It is advantageous to ' perform additional steps to determine whether the homologous recombination events result in disruption of the intended target gene sequence. The ZytA
transformation control can be used to confirm that the transformation system is functioning properly. For example, a phenotypic test for autolysin activity (lytA gene product) can be performed to determine that the exogenous lytA fragment is correctly integrated into the lytA site within the host genome. This typically involves flooding the culture plates containing transformants carrying the integrated lytA control vector with a solution of detergent, such as 0.1 % deoxycholate, which triggers cell lysis in lytA-intact cells (e.g., the cells that have not undergone homologous recombination).
After about 5-10 minutes the colonies with intact lytA will appear ghost-like due to cell lysis, and the colonies with a disrupted lytA gene will appear intact.
c) Polarity Analysis The ceg sequences that are confirmed to be essential for cell viability can be examined further by performing a polarity analysis to determine if the corresponding endogenous ceg sequence is organized in an operon. Polarity is an effect unique to prokaryotes and is the result of the operon organization of bacterial genomes. Many bacterial genes are arranged in operons in which multiple genes are under the control of a single regulatory sequence (e.g., a promoter) and are transcribed into a single mRNA transcript.
With respect to the orientation of multiple genes within an operon, the genes that are proximal to the regulatory sequence are said to be "upstream" genes and the genes that are distal are said to be "downstream",genes. For example, many operons contain genes encoding different proteins that catalyze discrete steps of a common biochemical pathway. Thus, any of the proteins that catalyze the steps of the pathway may be essential for cell viability.
The presence of operons in a bacterial host genome may influence the interpretations of the gene disruption results. For example, disruption of an upstream gene may be erroneously interpreted as affecting the expression of the disrupted gene but may, in fact, have expression affects on the intact downstream genes. Therefore, it is advantageous to perform a polarity analysis to determine if a ceg sequence is part of an operon.
A polarity analysis can involve performing an i~ vivo gene disruption procedure using as the disrupting sequence, a ceg sequence that includes the entire ceg coding sequence region but lacking expression regulatory sequences. This differs from the gene disruption assay, which involves the central region of the ceg sequence. The polarity analysis involves gene duplication via homologous recombination. For example, the pEVP-vector having the entire coding region of a ceg sequence can be used for the polarity analysis (Figure 2 A). The polarity analysis will yield different results depending on the organization of the endogenous target sequence within the host genome.
For example,. Figure 2 shows a schematic representation of the polarity test for operons, within a bacterial host cell. In Figure 2A, the recombinant vector, pEVP3, includes the CAT gene and the entire coding region of the ceg disrupting sequence. The "X"
in Figure . 2 indicates the recombinant pEVP3 vector undergoing homologous recombination with the target sequence. Two of the possible results of homologous recombination are shown in Figures 2 B and C.

In Figure 2 B, case l, if the endogenous target sequence is not organized in an operon, the integration event may yield: a functional target sequence (e.g., it is capable of expression); a duplicate non-functional target sequence that lacks a promoter;
and a ftulctional downstream gene (e.g., Gene B) that is controlled by its own promoter. The cells carrying this type of integrated target sequence can be recovered as viable cells that grow in the presence of chloramphenicol; this condition is termed "polarity negative".
In Figure 2 C, case 2, if the target sequence is organized in an operon, then the integration event may yield an integration site that is similar to that described for case 1, including: a functional target sequence; and a duplicate non-functional target sequence which is not functional. However, this integration event may also yield a non-functional downstream gene (e.g., Gene B) because expression of this downstream gene is controlled by a promoter located upstream of the insertion site. The cells that carry this type of integrated target sequence will be non-viable; this condition is termed "polarity positive".
Thus, the polarity analysis provides a method to determine whether integration of a recombinant vector into a target ceg sequence effects expression of downstream genes.
The ceg sequences disclosed herein (SEQ ID NOs.: 1-113, 227-331) encode gene products that are essential for viability in S. pheumohiae. Furthermore, many of these ceg sequences have been analyzed for the polarity effect and the results are presented in Table I. One subset of ceg sequences is classified as polarity negative (-), since the homologous recombination event did not effect the expression of downstream genes.
Another subset of ceg sequences is classified as polarity positive (+), since the homologous recombination event did affect the expression of downstream genes.
The ceg sequences that have not yet been classified as polarity positive or negative are indicated in Table I as a blank. For the ceg sequences that are classified as polarity positive, the genes downstream of the disrupted endogenous ceg sequences may or may not also be essential.

4) ASSAYS FOR IDENTIFYING CEG LIGANDS AND OTHER
BINDING AGENTS
The present invention provides screening methods for identifying agents that interact and/or bind to the CEG proteins of the invention, such as a ligand. An agent can be, for example, a natural product, a derived or synthetic chemical molecule, a polypeptide, a nucleic acid molecule, or a metal. The agents that interact with CEG proteins may cause bacterial cell death by disrupting the functions of CEG proteins, including, but not limited to, nucleotide biosynthesis, DNA replication, RNA transcription, protein translation, and/or cell wall biosynthesis. Accordingly, the present invention provides screening methods for identifying agents having antibacterial activity, such as agents that cause bacterial cell death by interacting with the CEG proteins. These antibacterial agents are useful for treating diseases and afflictions associated with bacterial infections.
Various methods can be used to discover agents having antibacterial activity, as determined by the ability of the binding agent to bind to a CEG protein and disrupt the function of the CEG protein. These screening methods include whole cell ih vivo assays as well as in vita°o assays with cellular components.
An ih vivo screening method for identifying ligands that bind CEG polypeptides can be performed in a whole cell assay. A typical method may be the use of whole bacterial cells to assess the 'antibacterial properties based on cell growth or viability. These methods can include methods for measuring cell growth and/or viability, for example, by optical density or zones of growth (Koch, A. L. et al., 1970 Ahal. Biochem.
38:252-259;
Biemer, J. J. et al., 1973 Ann. Clip. Lab. Sci. 2:135-140; Mahual of Clinical Microbiology; 7th edition, Murray, P. R. (ed), ASM Press), by growth inhibition in an agar assay (Murray, P. R., supra), or other means of detecting cell metabolism (Mychajlonka, M. et al., 1980 Antimicrob. Agents Chemothe~. 17:572-582), and are well known to those akilled in the art. In addition, there are molecular biology-based detection methods for use with whole bacterial cells, such as gene reporter assays, to monitor the effect of the ligand on specific targets (Slauch, J. M., et al., 1991 Methods Enzymol.
204:213-248). Examples of the reporter genes include, but are not limited to, beta-galactosidase, alkaline phosphatase, luciferase, and green fluorescent protein. For example, one embodiment provides a reporter system that monitors inhibition of DNA
synthesis by fusing a reporter such as beta-galactosidase (lack to genes known to be upregulated by the cessation of DNA synthesis as a result of the binding of ligands to the DNA synthetic apparatus. (Shurvinton, C. E., et al., 1982 Mol. Geh. Genetics 185:352-355; Rosato, A., et al., 1998 Ahtimic~ob. Agents Chemothe~. 42:1392-1396).
Alternatively, the. yeast two-hybrid system (Fields, S. and Song, O. 1989, Nature 340:245-246) may be adapted to screen for ligands that bind CEG polypeptides.
Generally, the yeast two-hybrid system is performed in a yeast host cell carrying a reporter gene, and is based on the modular nature of the GAL transcription factor which has a DNA
binding domain and a transcriptional activation domain. The yeast two-hybrid system relies on the physical interaction between a recombinant polypeptide that comprises the GAL
DNA binding domain and another recombinant polypeptide that comprises the GAL
transcriptional activation domain. The physical interaction between the two recombinant polypeptides reconstitutes the transcriptional activity of the transcription factor, thereby causing expression of the reporter gene. Either of the recombinant polypeptides used in the two-hybrid system can be generated to include a CEG polypeptide sequence to screen for binding partners of CEG. , Another method uses the bacterial CEG proteins as the basis for i~ vitro assay systems to detect binding agents. Typically, the iu vitro screening method comprises: a) generating the CEG protein of the invention, or membranes enriched in the CEG protein; b) exposing the CEG protein or membranes to a candidate agent; and c) detecting the interaction of the CEG protein with the agent by any suitable means.
Additionally, the screening methods may be adapted to automated high-throughput procedures, such as PANDEX.RTM Baxter-Dade Diagnostics, allowing for efficient high-volume screening of candidate agents.
An alternative method for screening potential ligands involves an in vitro binding procedure. Typically, the CEG proteins of the invention can be produced using recombinant DNA technology and host-vector systems as described herein. A
candidate agent is introduced into a reaction vessel containing the CEG protein, ox fragment thereof; the candidate agents may be detectable by methods such as, but not limited to, radioisotope or chemical labeling. Binding of the CEG protein by a candidate agent can be determined by any suitable means, including, for example, quantifying bound label versus unbound label using any suitable method. Binding of a candidate agent may also be detected by methods similar to an alternative physical method disclosed in U.S. Patent No. 5,585,277. In this method, binding of a candidate agent to a protein is assessed by monitoring the ratio of folded protein to unfolded protein, for example by monitoring sensitivity of the protein to a protease, or amenability to binding of the protein by a specific antibody against the folded state of the protein, or binding to chaperone protein, or by binding to any suitable surface.
The invention provides methods of identifying compounds that modulate (e.g., activate or inhibit) the function of a CEG polypeptide. Essentially any compound can be used in the assays of the invention. The preferred compounds are those that are soluble in aqueous or organic solutions. It will be appreciated by those of skill in the art that there are many commercial suppliers of chemical compounds that can be used in the methods of the invention, including Sigma Chemical Co. (St. Louis, Mo.), Aldrich Chemical Co.
(St.
Louis, Mo.), Sigma-Aldrich (St. Louis, Mo.), Fluka Chemika-Biochemica Analytika (Buchs, Switzerland), and the lilce.
The present invention provides methods for detecting compounds which are identified as modulators of CEG function. The methods of the invention can be performed using isolated CEG polypeptides, or use whole cells expressing the CEG polypeptide.
The steps, of the method using isolated CEG polypeptides include: contacting the isolated CEG polypeptide with a candidate compound; and determining whether the function of the CEG polypeptide is altered. The steps of the method using whole cells include:
contacting the whole cells with a candidate compound; and determining whether the cell dies, indicating the compound inhibited the function of a CEG polypeptide.

The preferred methods of the invention provide high-throughput screening assays for identifying compounds which modulate the function ~of a CEG polypeptide. The high throughput methods permit screening of large libraries of compounds. For example the high throughput methods can use automated assay steps. The assays can be performed in parallel on a solid support, as microtiter formats on microtiter plates in robotic assays are well known. A preferred embodiment of the methods includes adapting the methods to use microtiter plates or. pico- nano- or micro-liter arrays. In high throughput assays it is desirable to run positive controls to ensure that the components of the assays are working properly.
The high throughput screening methods of the invention include , providing a combinatorial library containing a large number of compounds (candidate modulator compounds) (Borman, S, C. & E. News, 1999, 70(10), 33-48). Such combinatorial chemical libraries can be screened in one or more assays to identify library members (particular chemical species or subclasses) that exhibit the ability to modulate the function of the CEG polypeptide (Borman, S., supra; Dagani, R. C. & E. News, 1999, 70(10), 51-60). The compounds, so identified, can serve as lead-compounds or can themselves be used as potential or actual therapeutics.
A combinatorial chemical library is a collection of diverse chemical compounds generated by using either chemical synthesis or biological synthesis, to combine a number of chemical building blocks, such as reagents. For example, a linear combinatorial chemical library, such as a polypeptide library, is formed by combining a set of chemical building blocks (amino acids) in every possible way for a given compound length (i.e., the number of amino acids in a polypeptide compound).
Millions of chemical compounds can be synthesized through such combinatorial mixing of chemical building blocks.
Preparation and screening of combinatorial chemical libraries is well known to those of skill in the art. Such combinatorial chemical libraries include, but are not limited to, peptide libraries (see, e.g., U.S. Pat. No. 5,010,175, Furlca, Iht. J. Pept. Pot. Res., 1991, 37:487-493 and Houghton, et al., Nature, 1991, 354, 84-88). Other chemistries for generating chemical .
diversity libraries can also be used. Such chemistries include, but are not limited to, peptoids (PCT Publication No. WO 91119735); encoded peptides (PCT Publication WO
93/20242);
random bio-oligomers (PCT Publication No. WO 92/00091); benzodiazepines (U.S.
Pat. No.
5,288,514); diversomers, such as hydantoins, benzodiazepines and dipeptides (Hobbs, et al., Proc. Nat. Acad. Sci. USA, 1993, 90, 6909-6913); vinylogous polypeptides (Hagihara, et al., J.
Amer. Chem. Soc. 1992, 114, 6568); nonpeptidal peptidomimetics with beta-D-glucose scafFolding (Hirschmann, et al., J. Amer. Chem. Soc., 1992, 114, 9217-9218);
analogous organic syntheses of small 'compound libraries (Chen, et al., J. Amen. Chem.
Soc., 1994, 116, 2661; Armstrong, et al. Acc. Chem. Res., 1996, 29, 123-131); or small organic molecule libraries (see, e.g., benzodiazepines, Baum C&E News, 1993, Jan. 18, page 33,);
oligocarbamates (Cho, ~ et al., Science, 1993, 261, 1303); and/or peptidyl phosphonates (Campbell, et al., J. O~g. Chem. 1994, 59, 658); nucleic acid libraries (see, Seliger, H et al., Nucleosides & Nucleotides, 1997, 16, 703-710); peptide nucleic acid libraries (see, e.g., U.S.
Pat. No. 5,539,083); antibody libraries (see, e.g., Vaughn, et al., Nature Biotechnology, 1996, 14(3), 309-314 and PCT/LTS96/10287); carbohydrate libraries (see, e.g., Liang, et al., Science, 1996, 274, 1520-1522 and U.S. Pat. No. 5,593,853, Nilsson, UJ, et al., Combinatorial Chemistry & High Throughput Sct~eeuiug, 1999 2, 335-352; Schweizer, F;
Hindsgaul, O.
Cur~eut Opinion Ih Chemical Biology, 1999 3, 291-298); isoprenoids (LT.S. Pat.
No.
5,569,588); thiazolidinones and metathiazanones (U.S. Pat. No. 5,549,974);
pyrrolidines (LT.S.
Pat. Nos. 5,525,735 and 5,519,134); morpholino compounds (U.S. Pat. No.
5,506,337);
benzodiazepines (U.S. Pat. No. 5,288,514); and other similar art.
Devices for the preparation of combinatorial libraries are commercially available (see, e.g., 357 MPS, 390 MPS, Advanced Chem. Tech, Louisville Ky., Symphony, Rainin, Woburn, Mass., 433A Applied Biosystems, Foster City, Calif., 9050 Plus, Millipore, Bedford, Mass.). In addition, numerous combinatorial libraries are themselves commercially available (see, e.g., ComGenex, Princeton, N.J., Asinex, Moscow, Ru, Tripos, Inc., St. Louis, Mo., ChemStar, Ltd., Moscow, RU, 3D Pharmaceuticals, Exton, Pa., Martek Bio sciences, Columbia, Md., etc.).

In the high throughput methods of the invention, several thousand different candidate compounds can be screened in a relatively short period of time. For example, each well of a microtiter plate can be used to run a separate assay against a selected potential modulator, or if concentration or incubation time effects are to be observed, every 5-10 wells can test a single modulator. Thus, a single standard microtiter plate can assay about 100 (96) modulators. If 1536 well plates are used, then a single plate can easily assay from about 100 to about 1500 different compounds. It is possible to assay many different plates per day; assay screens for up to about 6,000-20,000, and even up to about 100,000-1,000,000 different candidate modulator compounds are possible using the methods of g the invention.
The following examples are presented to illustrate the present invention and to assist one of ordinary skill in making and using the same. The examples are not intended in any way to otherwise limit the scope of the invention.

The following provides a general description of how a list of candidate ceg sequences was generated. The list was generated by selecting candidate ceg gene sequences from a Concordance web engine using the method described in: Bruccoleri, R.E., Dougherty, T.J., Davison, D.B. (1998) "Concordance analysis of microbial genomes" in:
Nucleic Acids Res 26:4482-4486.
Microbial Genomics CEG Discovery Process Summary Microbial Concordance Anal The entire genomic sequence data of various bacteria was acquired from several public and proprietary sequence database sources, including GTC (Genome Therapeutics Corporation), and TIGR (The Institute for Genomic Research).

Predicted ORFs from the genomic data were identified, translated, and stored.
, The desirable ORFs were at least 90 amino acid residues in length. Concordance analysis was performed among bacteria and various parameters were used to filter out genes with high similarity to eukaryotes.
Concordance Analysis The entire genomic sequence of various Eubacteria was acquired from several public and private sources. The proprietary PathoGenome System from Genome Therapeutics Corporation, Waltham, MA, USA contributed data. Public data was obtained from GenBank (http://ncbi.nlm.nih..-govt, The Institute for Genomic Research (TIGR), the Yeast Proteome Database, from Proteome, Inc. of Beverly, MA, and the Sanger Center of the Medical Research Council of the United Kingdom (http://www.sanger.ac.uk).
Additionally, the non-microbial sequence data used as a basis for comparison and data subtraction was obtained from a proprietary database, including the LifeSeq Database from Incyte Pharmaceuticals, Palo Alto, CA.
Where required, Incyte nucleotide sequences were translated into protein sequences in all six possible reading frames. GTC supplied predicted protein sequences with their data. In the case of other eubacterial nucleotide sequences, the program CRITICA
(Badger, J. and Olsen, G., 1999 "CRITICA: coding region identification tool invoking comparative analysis" in: Molecular Biology ahd Evolution 16:512-524). The sequences were stored in flat files on a Unix computer system. Each predicted amino acid sequence had to be greater than 90 amino acids.
Each predicted protein sequence was compared to every other sequence (an "all-against-all" comparison). The program used was FASTA (Pearson, W.R., "Flexible sequence similarity searching with the FASTA3 program package." Methods ih Molecular Biology 2000 132:1 ~5-219.) The parameters used were ktup=2, and all scores above the default cutoff were kept. The output was processed and stored in a PostGres 95 database (http://www.post~res~l.org). Graphical user interfaces, using web browser technology, were constructed to query the database.

A Concordance Analysis was performed on the data. The question used to generate the dataset was show all Streptococcus pneumohiae open reading frames with a similarity greater than or equal to 30% overall protein sequence identity to both selected gram-positive and/or gram-negative bacteria in the database. The data was further required not to match yeast or human sequences at greater than 30% overall protein sequence similarity. The resulting dataset included a list of more than 400 conserved amino acid sequences having known or unknown function. The amino acid sequences having unknown functions formed the basis 'of a list designated Conserved Unknown Reading Frames, or CURFs which is a subset of the total list of CEGs (e.g., CURFs includes known and unknown).
The resulting list of conserved genes (e.g., more than 400 sequences) was used as a basis 1 S for selecting and screening bacterial gene sequences that are essential for cell viability.
The Concordance system was designed to permit high-throughput identification of conserved gene sequences in the database. (Bruccoleri, R, Dougherty, T, and Davison, D.
1998 "Concordance analysis of microbial genomes" Nueleic Aciels Res. 26:4482-4486.) Data Curation And Analysis Exact N-terminal and C-terminal translational start sites of genes were identified by pairwise similarity searches, multiple sequence alignments. Ribosome binding sites, terminators, nearby genes, operons were identified.
The resulting list of conserved genes was used as a basis for selecting and screening bacterial gene sequences that are essential for cell viability. This Concordance system was designed to permit high throughput use of the conserved gene sequences contained .
on the list. A set of Knockout PCR primers were generated, based on the list of conserved genes, for the purpose of use in the gene disruption procedure described below. The PCR primers were designed to amplify a central 300-500 by region of the ceg (to prevent generation of a functional copy of the ceg gene following integration), ordered electronically, the primers were placed in a 96-well format, and used in the gene disruption procedure as described below.

The following provides a description of the procedure to generate recombinant vectors of pEVP-3 having inserts of candidate ceg nucleotide sequences. The Knockout primers generated by the method described in Example 1 above were used to generate DNA
fragments comprising candidate ceg sequences.
Genomic PCR Krioclcout Target Fragment Generation 96-well plate format were set up (36 ~l H20 , 5 ~,1 lOX VentTM buffer, 1 ~,1 gene specific, knockout forward primer (0.5 ~,g/ql), 1 ~,1 gene specific knockout reverse primer (0.5 ~.gl~l), 0.5 ~,l VentTM DNA polymerase (2000 U/ml New England Biolabs, Beverly, MA), 1.5 ~1 each dNTPs (lOmM; 6.0 ~,1 total), 0.5 ~.1 S. pneumoniae chromosomal DNA
(0.5 ~g/~1), 50 ~,l total volume/reaction).
The nucleotide sequences of the forward and reverse lcnoclcout primer pairs were generated from the nucleotide sequence information obtained from the Genomic Therapeutics Corporation database for Streptococcus pneumoniae. The primer pairs were each used in a PCR reaction to generate a unique internal (e.g., central region) fragment of the candidate gene targeted for knockout.
The PCR program was set in the PCR machine (Initial 95 °C - 5 minutes:
30 Cycles of:
95 °C - 1 minute, 58 °C - 1 minute,. 72 °C - 30 seconds;
Final, 72 °C - 10 minutes, 4 °C -hold indefinitely). 5 ~l of each reaction was run on an 0.8% agarose gel after purifying fragment over PCR purification lcit (Qiagen) to visualize the fragments then ligation reactions were performed.

Ligation Reactions proceeded (set up in 96-well plate format (10.0 ~1 genomic PCR
fragment (generated from step 2 above), 1.0 ~1 pEPV-3 SmaI-cut vector (1: 10 dilution of vector DNA at SO-100 ng/p,l), 1.5 ~,1 lOX ligation buffer (New England BiolabsTM), 1.0 ~,1 T4 DNA Ligase (New England BiolabsTM 400,000 U/ml), 1.5 ~,l ddH20, 15.0 ~,l total reaction volume):
Reactions were allowed to incubate in 96-well plate at .14 °C overnight in the PCR
machine. Transformations. into E. coli for in vivo amplification were proceeded the following day.
The nucleotide sequences of the forward and reverse primer pairs used for the polarity test were generated in a similar manner, from the nucleotide sequence information obtained from the Genomic Therapeutics Corporation database for Streptococcus -pneumoniae. The primer pairs were each used in a PCR reaction to generate a unique fragment of the candidate gene targeted for the polarity test. The fragment generated for the polarity test included the entire ceg coding sequence region but lacking the expression regulatory sequences.
Transformation into E. coli (strain LE392~
The next day, 3 ~l of above ligation mix was used per transformation reaction plus 50 ~.l LE392 competent cells. Reactions were set up in 96-well plate format;
incubated on ice for 30 minutes; heat-shocked at 42° C for 90 seconds; and incubated on ice 2 minutes;
100 ~1 SOC media (Gibco BRL) was added; then incubated at 37° C on platform shaker for 1 hour; plated on LBlchloramphenicol (13.0 ~.giml) agar plates for constructs over night at 37° C with plates inverted and proceeded with colony PCR to confirm constructs.
The universal primers flanking the insert site in pEVP-3 were used for PCR
amplification.
The colony PCR involved the following. 96-well plate format was set up (36.5 ~,1 HaO, 0.5 q.1 pEPV3 forward primer (0.25 ~g/ql), 0.5 ~,1 pEPV3 reverse primer (0.25 ~,g/ql), 1.5 ~l each (6.0 ~,l total) dNTP,s (10 mM), 0.5 ~.l VentTM DNA polymerase, 5 ~l 10~ VentTM
buffer, 1 ~,1 of a 1:50 cell dilution, 50 ~,l total volume).
pEPV3 forward primer: 5' CATCAAGCTTATCGATACCGTCG 3' (SEQ ID N0:437) p EPV3 reverse primer: 5' CACAGTAGTTCACCACCTTTTCCC 3' (SEQ ID N0:438) Colonies of E. coli LE392 were picked onto ~ a master plate of LB + 13 ~g/ml chloramphenicol (incubate throughout the day at 37° C) and then into 50 ~1 H20 which has been placed into a 96-well plate. 1 ~.1 of this dilution was used in above PCR reaction (if the 96-well dilution plate is kept you will not need to prepare a master plate). Cultures for minipreps of plasmid candidates may be prepared directly from the cell dilutions.
The PCR program was run (95 °C - 5 minutes, 30 Cycles of: 95 °C -1 minute, 58 °C - 1 minute, 72 °C - 30 seconds, 72 °C.- 10 minutes; 4 °C -hold).
A 10 ~.l/ reaction was run on a 1.0 % TBE gel. A gel designed for 96 well plates and a multichannel pipettor were used to ease loading of the sample rows. The gel was run and stained with ethidium bromide. The positive clones were identified with appropriate molecular size insert(s), amplified by the flanking pEVP-3 primers.
Minipreps Of Plasmids To Identify Cells Carryin~ The Pevp-3 Vector With An Insert The constructs that carried an insert were identified. The constructs having an insert were inoculated into a 5 ml LB/Cm culture, and incubated over night at 37 °C with aeration. Miniprep plasmid DNA was prepared by a standard procedure. The miniprep DNA was digested with appropriate restriction enzymes to confirm the presence of the insert (enzymes flank SmaI site in pEVP-3) (10 ~1 miniprep DNA, 2 ~,l 10 ~
buffer, 1 ~,1 XbaI, 1 ~,1 XhoI, 6 ~l ddH20; 20 ~,1 total volume for digest).

To confirm the presence of an insert, the digest reactions were electrophoresed on an agarose gel and the gel was stained with ethidium bromide. The positive clones were used for the S. pneumoniae KNOCKOUTS procedure.
The confirmatory PCR reactions, using knock out-specific primers (quality control step) involved 35.5 ~l H20, 5 ~1 10 ~ VentTM buffer, 1 ~1 knockout forward primer (0.5 ~,gl~,l), 1 ~,1 knockout reverse primer (0.5 ~,g/~l), 0.5 ~.l VentTM (6.0 ~,1 total) DNA
Polymerase (2000 U/ml), 1.5 ~.l each dNTPs (lOmM, 6.0 ~l total), 1.0 ~l miniprep DNA from test clone, 50 ~.1 total reaction volume. The PCR program was as follows: 95 °C for 5 minutes, 30 Cycles of: 95 °C for 1 minute, 60 °C for .l minute, 72 °C for 30 seconds, 72 °C for 10 minutes, hold at 4 °C. The presence of the correct-sized insert was confirmed by agarose gel electrophoresis and ethidium bromide staining. The confirmed clones were used for the S pheumoniae gene KNOCKOUT procedure. Glycerol stocks were made of all positive E. coli LE392 constructs and frozen at - 80 degrees C.

The following provides a description of the high throughput gene disruption procedure used in S. pneuhomiae strain (e.g., gene knockout procedure). The candidate ceg fragments that were generated by the method described in Example 2 were used in the gene disruption procedure in order to identify ceg nucleotide sequences that are required for cell viability.
Reactions were set up in a 1.5 ml eppendorf tubes or 96 well plate (1 ~,g total of miniprep pEVP-3 + insert DNA (usually 10 ~,1 of Qiagen miniprep DNA); then 200 ~l of S.
pheumov~iae (strain Rx-1) competent cells diluted 1:10 in competence media was ,added (1 ml of competence media = 980 ~.l Todd H~yvitt (Difco Laboratories) with 0.5% yeast extract, 20 ~1 10% BSA, 1 ~.1 10 % CaCl2, and 0.5 ~1 (200 ~,g/ml) Csp-1 competence peptide).

Controls were run with each I~NOCI~OUT experiment and involved 1 ~g pEPV3 Lyt A
construct = positive control (non-essential), or 1 ~g pEPV3 Fts Z construct =
negative control (essential). Then the 96 well plates and controls were incubated at 37 °C for 2.5 to 3 hours in 37 °C room without shaking. The 200 ~l of the samples were plated on Todd Hewitt agar plates with 0.5% yeast extract and 2 ~g/ml chloramphenicol.
The samples were incubate over night at 37 °C in 5% COZ incubator.
Control plates were checked for presence of colonies (pEVP-3::lytA) and no growth (pEVP-3::ftsZ).
Plates were examined for growth (ca. 70-150 colonies) designating nonessentials and zero colonies designating essential genes.
The polarity test was performed in a similar manner, using the polarity fragments described in Example 3.

The following provides a description of the autolysin procedure used to determine that the non-essential control samples of S pheumouiae contain a disrupted lytA
gene.
Phenotypic Autolysin Test The culture plates containing transformants carrying the lytA control vector were flooded with 0.1% deoxycholate in H20. The plates were observed after 5-10 minutes.
Plates with "ghosts" indicated intact lytA gene, or plates without "ghosts" indicated a disrupted lytA gene. The "ghost" phenomenon is due to detergent triggered autolysis of the cells, causing a gradual fading of the colonies.
The detergent treatment triggers the autolysin in lytA intact cells; it cannot trigger the autolysin (lytA gene product) in lytA disrupted cells. Colonies with intact lytA "ghost" in 5-10 minutes due to massive pneumococcal cell lysis.

The following provides a description of the procedure used to express the CEG
proteins (e.g., designated CFE proteins) in E. coli cells.
CEG Protein Production Full-length ceg gene were inserted into pET-21 expression vector using the E.
coli BL21 ~,DE3 expression system using the following method:
For each ceg, custom primers were used to insert N- and C- termini into vectors such that the 5' end (N-terminus of the CEG) is positioned properly for expression behind the T7 promoter and optimally placed with regard to the pET ribosome binding site.
The pET
vectors contain an Ndel site which allows positioning of ATG start site in the vector. In cases where the ceg sequence contains an internal Ndel site, blunt ligation of the ceg PCR
fragment into the vector is accomplished via Klenow fill-in of the Ndel site.
In many cases, primers were also designed such that the ceg 3' (C-terminus of the expressed protein) will contain an in-frame extension of 6X-histidine residues, encoded in the vector sequence of pET-21. The individual cegs were PCR amplified via custom designed primers as described above. Both ceg PCR and~vector DNA were digested with appropriate restriction enzymes. The full-length ceg were ligated into the pET
expression vector. The ligation mixture was transformed into competant E coli ~,DE3 cells and selected for transformants on LB agar with 50 ~,g/ml ampicillin. Positive insert bearing clones were screened via minipreps of the plasmids and size analysis on 0.8% agarose gels, with detection by ethidium bromide staining, as above.
Protein Production The proper reading frame of each ceg inserted into pET-21 is verified by DNA
sequencing.

A small (2-S ml) test culture of E coli BL21 ~,DE3 with the insert-bearing plasmid is tested for protein expression by IPTG induction of the expression vector for 1-2 hours.
The expression is verified by SDS-Polyacrylamide Gel Electrophoresis analysis of a whole cell extract (SDS extract of 0.5-1 ml of cells treated at 100 °C
for 5 minutes) to determine whether the protein is over-expressed and migrates at the correct predicted molecular weight.
The protein is overproduced and purified. via the following method. A large scale (500-1000m1) culture of E coli is grown to early logarithmic phase in broth (e.g., LB broth) and protein .expression induced for 2 hours with IPTG (isopropyl-D-thiogalactoside).
The cells are harvested by centrifugation (8000 X G; 15 minutes) and the cell pellets resuspended in 20 ml. of buffer. The cells are lysed by sonication, and the supernatant fluid centrifuged at low speed (5000 X G, 15 min.) to remove unbrolcen cells:
The supernatant fluid, containing the over-expressed protein is subjected to Ni-NTA affinity column chromatography (Quiagen, Inc., Chatsworth, CA). The 6X-histidine residues linked at the C-terminal end of the CEG proteins permit rapid protein purification via selective binding to a Ni-NTA resin column. The protein-bound Ni-NTA resin was to remove contaminants, and the bound proteins subsequently eluted with imidazole and recovered. It is possible to upscale this procedure to larger volumes for higher yields of proteins.

The following provides a description of the methods used to purify all 2CEG
polypeptides (e.g., 2CFE polypeptides #19-117; SEQ ID NOS:349-436) having a histidine tag at their C-terminal ends. The 2CEG polypeptides having the his-tags were produced by the methods described in Example 5, supra. As an example, results of purification of 2CFE 75 polypeptide are presented.

Production Of The CFE Polypeptides The BL21 ~,DE3 cells harboring recombinant pET-21 vectors carrying a 2CFE
nucleotide sequence (SEQ ID NOS:244-331) were cultured in LB broth containing ampicillin.
When the A6oo reached approximately 0.6, protein production was induced by adding 1.0 mM of IPTG, the cells were cultured for an additional .2 hours. The cell pellet was collected by centrifugation, and the collected cell pellet was sonicated in Solution A (50 mM NaP04; 300 mM NaCI, pH 8.0). The sonicated cells were centrifuged at 10,000 . RPM to remove the debris.
Purification Of The CFE Poly~e tp ide The supernatant was diluted with Solution A, loaded onto a Ni-NTA column (Quiagen) equilibrated with Solution A; the column bed size was 2.5 x 25 cm, and the flow rate was approximately 3.0 ml/minute. The 2CFE protein was eluted using a linear gradient of imidazole, using 0-250 mM in 450 ml, flow rate approximately 3.0 ml/minute.
The eluted samples were collected as 22 ml fractions per tube and the eluted samples were monitored using spectrophotometry. The amount of protein in the eluted fractions was estimated using the Bradford method (Bradford, M. M., 1976 Ahal. Biochem.
72:248) and the samples were run on an SDS-PAGE gel (Novex EC6008) (Figure 3 A). Fractions were selected for pooling based on the results of the SDS-PAGE gel. The pooled fractions were concentrated using a 10,000 MW Centricon (Amicon) to approximately 5 ml. .
The 2CFE 75 polypeptide, a precipitate formed and was redissolved upon increasing the sample volume and removing the imidazole by repeated concentration in 50 mM
Tris, 100 mM NaCI, pH 7.5. Varying amounts of the 2CFE 75 polypeptide were diluted in either 20 mM Tris, 20 mM ICI, pH~ 7.5 or 20 mM Tris; 20 mM MgCl2, pH 7.5 at concentrations of 12, 24, or 36 ug/ml. The diluted samples were electrophoresed on an SDS-PAGE gel under non-reducing conditions (Figure 3 B). The results of Figure suggests that 2CFE 75 forms a multimer.

The following provides a description of the methods used to purify CEG
polypeptides that lack a histidine tag (e.g., 2CFE polypeptides #1-17; SEQ ID NOS:332-348).
As an example, the results of purification of CFE 3 polypeptide are presented.
Purification of the CFE 3 Poly~eptide The 2CFE 3 polypeptide was produced using the large scale IPTG-induced method described in Example 5, supra. The 2CFE 3 (SEQ ID N0:334) polypeptide lacks a C-terminal histidine tag. The 2CFE 3 polypeptide was purified using a 2-column procedure. The 2CFE 3 polypeptide preparation was eluted from a 26/10 Q
Sepharose column (Pharmacia) using a 0-1.0 M NaCI gradient, 2 ml/minute flow rate, and the gradient size was 1 liter. Then the 2CFE 3 polypeptide was eluted from a hydroxyapatite Bio-gel column (Bio-Rad) using a 5-200 mM potassium phosphate (pH 8.0) gradient, the flow rate was 0.3 ml/minute, and the gradient size was 300 ml. A sample of the preparation was run on a polyacrylamide gel (Figure 4).

The following provides a description of the size exclusion chromatography methods used to estimate the molecular weight and determine whether the CEG polypeptides oligomerize. The CFE polypeptide may olimerize to form monomers, dimers, tetramers, hexameric rings, or other oligomeric forms.
Size exclusion chromatography was performed on all isolated 2CFE polypeptides #s 1-117 (e.g., SEQ ID NOS:332-436). This method was performed using various types of columns, depending on the particular 2CFE polypepeptide tested.

The Biosil SEC-125 HPLC Gel Filtration column (BioRad Laboratories, Inc) was used, for example, to characterize CFE 8. The mobile phase was 0.2 M KH2P04, 0.9%
NaCI
pH 6.8.
The Phenomenex 600 x 7.5 mm Biosep SECS 3000 column was used, for example to characterize 2CFE 21 and 39. The mobile phase for size exclusion was 50 mM
Na2HP04, pH 7.0 and 150 mM NaCI run at 1 ml/minute in a Gilson HPLC system, with protein detection at 280 nm.

The following provides a description of the computer-aided methods used to search for similarities between the amino acid sequences of the CEG polypeptides and sequences available through public and proprietary databases. In many cases, the function of the CEG polypeptides was suggested by the results of the similarity searches. The function of some of these CEG polypeptides has been confirmed by performing additional analyses. Table V provides a list of the suggested and confirmed functions of CEG
polypeptides designated CFEs #1-117.
The. putative fiulction of the CFE polypeptides were determined using computer-aided bioinformatic approaches, including distant homologies, motif searching, or predictions based on statistical rules. For example, the distant homology approach involved pairwise or multiple sequence 'alignments, employing tools such as FASTA, and Psi-BLAST.
The motif searching approach involved using sophisticated hidden Markov models.
The approach based upon predictions of statistical rules involved prediction of transmembrane regions, coiled-coil, and other structural motifs. These approaches have been reviewed in Computational Methods In Molecular Biology 1998, eds. Salxber, S.L., Searls, D.B. Searls, and Kasif, S. , Elsevier, and in Bioinformatics: A Practical Guide To The Analysis Of Genes And P~~oteins 1998 eds Baxevanis, A. D. and Francis Ouellete, B.F. , Wiley-Interscience.

Global sequence similarity searches were performed using the amino acid sequences of all the conserved essential gene sequences (e.g., CFEs 1-117; SEQ ID NOS:114-226) to search, against a non-redundant protein database using the BLAST2 algorithm (Altschul S.F., et al., 1997 Nucleic Acids Res. 25(17):3389-3402). In a similar search, similar sequences were identified in the Concordance database using the "Neighbor"
function (Bruccoleri R. E., Dougherty T.J., Davison D.B. 1998 Nucleic Acids Res.
26(19):4482-4486). To determine if the predicted amino acid sequences were full length and in the proper reading frame, BLAST-type searching and CLUSTAL multiple sequence alignments (Higgins D.G., et al., 1996 Methods Enzymol. 266:383-402) were used.
Local sequence similarity searches were performed, by searching for Prosite (Hofmann K., et al., 1999 Nucleic Aeids Res. 27(1):215-219) and Pfam motifs (Bateman A., et al., 2000 Nucleic Acids Res. 28(1):263-266). Additionally, the amino acid sequences of the CFEs were analyzed by performing protein threading analyses using the ProCeryon fold recognition program (Sippl, et al., 1992 P~otei~s 13:258-271; Sippl, J. 1993 J. Comp.
Aided Mol. Design 7:473-501; www.proceryon.com) and Geneformatics.
In bacteria, many operons include genes encoding different proteins that catalyze discrete steps of a common biochemical pathway. Therefore, the operon structures in S
pneumoniae was compared with that in other bacteria in order to predict the function of CFE polypeptides.
Additionally, analysis of bacterial metabolic pathways were performed using Pathway Tools from DoubleTwist, based on the EcoCyc system (Karp P.D., et al., 1999 Nucleic Acids Res. 1999 27(1):55-58). This analysis was used to .predict which CFEs mediate various steps of the pathways.
When the sequence identity between a CFE polypeptide and the annotated database (e.g., SwissProt, Genbank) was low (e.g., sequence identity less than about 30%), a Protein Threading (e.g., fold recognition) method was used to predict similarities in the folded protein structure of CFE polypeptides in the absence of a high level of sequence similarity with proteins in the databases (review by Teichmann, et al., 1999 Current Opinion in St~uctu~~al Biology 9:390-399). The Protein Threading method predicts the compatibility of a query sequence (e.g., CFE polypeptide sequences) with each of the folds in a library of known protein structures. The library of known protein structures as developed, maintained, and updated throughout the search process.
A list of potential structural folds, onto which each query was compatible, was generated for all CFE polypeptides (e.g, SEQ ID NOS:114-226). The fold assignments for each query were used to generate pairwise sequence alignments. The pairwise sequence alignments were used to generate protein models of the query polypeptide (e.g., CFE
polypeptides).
The pairwise sequence alignments were also used to compare the position of critical residues of the structural template with the query polypeptide. The list of critical residues was generated by using multiple sequence alignments derived from a structural classification of proteins to generate a conservation profile which provided sequence-specific positions conserved across a homologous family of protein folds.
Comparative modeling was used to search the model of the query polypeptide for the critical residues and determine whether the structural and functional motifs are conserved in the query protein.
Conservation of structural and fiuictional motifs permitted assignment of putative structure and function to a query polypeptide sequence.
The Protein Threading method was used to search for putative folded structure and function for all CFE polypeptides (SEQ ID NOS:114-226). The CFE polypeptides having significant sequence identity (e.g., more than 30%) to known proteins were assigned putative functions with a high level of confidence.
EXAMPLE ZO
The following provides a description of the methods used to characterize purified, CFE
1 O 1 polypeptide. The 2CFE;1 O l polypeptide mediates the conversion of pantothenate to 4' phosphophantothenate, and is predicted to be a pantothenate kinase.

Computer-Aided Comparison The computer-aided comparison, as described in Example 9 supra, suggests that the amino acid sequence of the CFE 101 polypeptide (SEQ ID N0:210) is 42% similar to the amino acid sequence of the coaA protein of E. coli. Thus, CFE 101 may be a pantothenate kinase, which mediates the conversion of pantothenate to 4' phosphophantothenate (Figure 5).
Circular Dichroism and Circular Dichroism Thermal Melt Anal,~is Circular dichroism and circular dichroism melt methods were used to determine the folded structure of the expressed and isolated 2CFE polypeptides. For example, this method was used to characterize the folded structure of isolated 2CFE 101 (SEQ
ID
N0:421 ).
The starting concentration of the 2CFE 101 polypeptide was such that ODZOS was approximately 1.5, and the OD28o was approximately 0.05 (e.g., 0.05 to 0.1 mg/ml). The starting concentration of 2CFE 101 was approximately 344 ~M in 50% glycerol, 50 mM
Tris, 100 mM NaCI, 5 mM MgCl2, 0.5. mM EDTA, at pH 7.5. The polypeptide was diluted to a final concentration of 7 ~.M, as determined by absorbance at AZSO, in 20 mM
Na-phosphate, 100 mM KCI, at pH 7Ø The circular dichroism analysis was performed using quartz cuvettes, the instrumentation was from JASCO (Model J-720), the readings were performed at 25 degrees C (Figure 6 A). The band width was 1 nm, the sensitivity was 20 mdeg, the response was 0.25 seconds, the scan speed was 50 nm/minute, and the step was 0.5~. The circular dichroism thermal melt analysis was performed at a range of between 0 and 100 degrees C (Figure 6 B). Additionally, the circular dichroism was performed comparing monomer and aggregate pools of 2CFE 1 O 1.

Size Exclusion Anal Size exclusion chromatography methods were performed using the Biosil SEC
column, as described in Example 8 supra. The results suggest that the 2CFE 101 polypeptide forms monomer (40,200 Da) and oligomers (194,000 Da). The specific activity of the monomer and oligomeric forms of 2CFE 1 Ol were determined, as described below.
Biochemical Assays The biochemical assays of the 2CFE 101 polypeptide was based on the PKJLDH
coupled enzyme assays described by Vallari, D. S., et al. (1987 J. Biol. Chem.
262:2468-2471) and Song, W. -J., et al., (1994 J. Biol. Chem. 269:27051-27058).
Briefly, the assay was performed as follows. The reaction included: 885 ~,1 of 0.1 M
Tris-HCl (pH 7.6), 25 ~,1 NADH (14.1 mM), 20 ~,l ATP (10.7 mM), 50 ~,1 phospho-enol-pyruvate (56 mM), 5 ~,l LDH/PK (lactose dehydrogenase/PK; Sigma, catalog # P-0294, 60 U/ ml PK, 1050 U/ml LDH), 5 ~.l of the 2CFE 101 polypeptide (9 mg/ml in 50 mM
Tris-HCI, pH 7.5, 100 mM NaCI which was diluted to 4.5 mg/ml in 50% glycerol).
The reaction was started by adding 10 ~,l pantothenate (100 mM; Sigma, catalog #
P2250).
The production of ADP in the reaction was monitored by measuring the absorbance a 340 nm. The results in Figure 8 show that the, 2CFE 101 polypeptide mediates ADP
production in the presence of pantothenate and ATP. The Km of pantothenate (n=4) was 144 (~16.5) ~,M, the Vm~ of the 2CFE 101 polypeptide (n=4) was 2.04 (~0.25) ~.M miri 1 mg 1. The. monomer form has a specific activity of approximately 1.7 ~.M miri 1 mg 1.
The oligomeric form has a specific activity of 0.26 ~,M miri 1 mg 1.
Alternatively, the 2CFE 101 polypeptide can be tested in an assay that monitors the conversion of pantothenate to 4'-phosphopantothenate. The same reaction described ' above can be used, except 14C-labeled pantothenate is used. The . reaction can be monitored by measuring the amount of 14C-labeled 4'-phosphopantothanate produced.

The following provides a description of the methods used to characterize purified, CFE
39 and CFE 21 polypeptides, carrying a C-terminal histidine 6-tag. The methods include helicase reactions, in which synthetic Holliday Junction templates are resolved into duplex structures. In one method, helicase reaction was monitored using radiolabeled templates. In another method, the helicase assay was adapted for use in a high throughput assay employing fluorescence labeled templates.
Computer-Aided Comparison The computer-aided comparison, as described in Example 9 supra, suggests that the CFE
39 polypeptide (SEQ ID NO: 148) is an RuvA homologue. The comparison also suggests that CFE 21 (SEQ ID N0:132) is an RuvB homologue.
Previous studies by Parsons and others have shown that RuvA and RuvB proteins, in E.
coli, promote branch migration or movement of Holliday Junctions during genetic recombination and DNA repair (Parsons, C. A., et al., 1992 P~oc. Natl., Acad.
Sci. USA
89:5452-5456; Tsaneva, L -R., et al., 1993 Proc. Natl., Acad. Sci. USA 90:1315-1319;
Muller, B., et al., 1993 J. Biol. Chem. 268:17179-17184; Mitchell, A. H. and S. C. West 1996 J. Biol. ~ Chem. 271:19497-19502; Parsons, C. A. and S. C. West 1993 J.
Molec.
Biol. 232:397-405; Tsaneva, I. R., et al., 1992 Molec. Gee. Geuet. 235:1-10;
Mitchell, A.
H. and S. C. West 1994 J. Molec. Biol. 1994 243:208-215).
Size Exclusion Chromatography Size exclusion chromatography was performed on 2CFE 39 (SEQ ID N0:366) and 21 (SEQ. ID N0:350) using the Phenomenex 600 x 7.5 mm Biosep SECS 3000 column, as described in Example 8 supra. Protein standards (BioRad) were used to calibrate the column, including thyroglobulin (670,000 Da), gamma globulin (158,000 Da), ovalbumin (44,00 Da), myoglobin (17,00 Da), and B-12 (1350 Da).

The results indicate that 2CFE 39 (RuvA) forms tetramers and 2CFE 21 (RuvB) forms a hexameric ring structure. Selected eluted samples were electrophoresed on a polyacrylamide gel (Novagen) (Figure 9).
The Holliday Junction Analysis Using Radiolabeled Templates The Holliday Junction analysis was performed using radiolabeled, synthetic, asymmetrical, Holliday Junction templates, as described in Hiom, K. and S. C.
West 1995 Cell 80:787-793. The Holliday Junction templates were produced by annealing together four separate, single-stranded, oligonucleotide strands to form four-stranded structures (e.g., the Holliday Junction template). The Holliday Junction templates were reacted with the 2CFE 39 and 2CFE 21 polypeptides, in a helicase reaction, to test their ability to generate two duplex structures.
Producing the Synthetic Holliday Junction Templates The asymmetrical Holliday Junction templates were produced by annealing the following oligonucleotide sequences:
Oligonucleotide strand 1:
5'-CCAGTGATCACATACGCTTTGCTAGGACATCTTGATATCAGCCCACGTT
CACCCGCCTACCAGTGCCACGTTGTATGCCCACGTTGACC-3' (SEQ ID N0:438) Oligonucleotide strand 2:
5'-GGGTCAACGTGGGCATACAACGTGGCACTGGTAGGCGGGTGAACGTGGG
CTGATATCAAGATGTCCATCTGTCCGTTCATCTATGACGT-3' (SEQ ID N0:439) Oligonucleotide strand 3:
5'-AACGTCATAGATGAACGGACAGATCATGGTGCTTTTAAAGTCTAGAGAC
TATCGAGCATTAGTACCAGTATCGAATCCGTCTTGTCAA-3' (SEQ ID N0:440) Oligonucleotide strand 4:
5'-TTTGACAAGACGGATTCGATACTGGTACTAATGCTCGATAGTCTCTAGAC
TTTAAAAGCACCATGTAGCAAAGCGTATGTGATCACTG-3' (SEQ ID N0:441) Oligonucleo'tide strand 3 was labeled at the 5' end using approximately 300 ng of oligonucleotide strand 3, 1 ~l lOx Phosphate Buffer, 5 ~.13aP ATP, 1 ~,l T4 polynuclotide kinase (Gibco-BRL)), in a 10 p1 volume, and the reaction was performed at 37 degrees C
for 30 minutes. The reaction was loaded onto a G50 column to remove the unincorporated radiolabel. The final concentration of the radiolabeled oligonucleotide strand 3 was approximately 15 ng per ~,1.
Approximately equimolar amounts of the four oligonucleotide strands were annealed (e.g., hybridized). The annealing reaction included: 5 p1 Annealing Buffer (200 mM
Tris-Cl pH 8.0, 100 mM MgCl2, 1 M NaCI, 10 mM DTT); 450 ng of radiolabeled oligorlucleotide strand 3; and 1000 ng each of oligonucleotide strands l, 2, and 4; in 50 ~.l total reaction volume. The control annealing reaction included: 5 ~.l Annealing Buffer, 60 ng radiolabeled oligonucleotide strand 3; 1000 ng oligonucleotide strand 4;
in 50 p,1 total reaction volume. Annealing was performed at 95 degrees C for 5 minutes, degrees C for 30 minutes, 42 degrees C for 30 minutes, and room temperature (e.g., between about 23 to 27 degrees C) for 30 minutes to generate the synthetic Holliday Junction templates. The synthetic Holliday Junction templates were gel or column-purified to remove the duplex and non-annealed products. As a control, oligonucleotide strands 3 and 4 were annealed to form duplex structures. The synthetic Holliday Junction templates and duplex structures were stored at -20 degrees C.
CFE 39 and CFE 21: The Helicase Reaction Using Radiolabeled Tem fates The helicase reaction was performed to determine whether 2CFE 39 and 2CFE 21 resolved the synthetic Holliday Junction templates into duplex structures. The helicase reaction was performed as follows. A 50 pl total reaction volume included: 25 p,l of 2x Reaction Buffer (50 mM Tris-Cl pH8.0, 30 mM MgCla, 2 mM ATP); 1 ~,l synthetic Holliday Junction template (36 ng); 2 ~.1 2CFE 39 (1 ~.M); and 2 ~,l 2CFE 21 (1 ~,M).
The reaction was incubated at 37 degrees for 30 minutes. The reaction was stopped by adding 5 ~l Stop Buffer (100 mM Tris-Cl pH 7.5, 5 mg/ml Proteinase-I~, 5%
SDS). The stopped reaction was returned to 37 degrees C for 5 minutes. The helicase reaction was loaded onto and run on a non-denaturing, 12% PAGE, Tris-glycine gel.
The results shown in Figure 10, lanes 6, 7 and 8, indicate that the 2CFE 39 and 2CFE 21 polypeptides resolved the synthetic Holliday Junction templates into duplex structures.
CFE 39: The Helicase Reaction It has been previously shown that E. coli RuvA binds to Holliday Jmction templates (Parsons, C. A., et al., 1992 P~oc. Natl., Acad. Sci. USA 89:5452-5456). The ability of S.
pneumohiae CFE 39 to bind to a Holliday Junction template can be tested by employing the helicase assay described herein. The results of the helicase assay can be monitored by performing a gel shift assay and/or capillary electrophoresis. The presence of a Holliday Junction template bound to 2CFE 39, which migrates more slowly than the Holliday Junction template alone, would indicate that S. pheumov~iae 2CFE 39 binds to Holliday Junction templates.
CFE 39 and CFE 21: Holliday Junction Analysis Using Fluorescent-Labeled Templates The helicase reaction described herein was performed using Holliday Junction templates having one oligonucleotide strand labeled with a fluorescent agent and another strand labeled with a quenching agent. The 5' fluorescent end and the 3' quenching end of the strands that make up the Holliday Junction templates are in proximity to each other, resulting .in a non-fluorescent template. When the Holliday Junction templates are resolved into duplex structures, the fluorescent and quench ends are not in proximity to each other, resulting in fluorescence.

The Holliday Junction templates used to perform this experiment comprised the following: the 5' end of oligonucleotide strand 1 was labeled with a fluorescein (e.g., the fluorescent agent), and the 3' end of oligonucleotide strand 4 was labeled with DABCYL
(e.g., the quenching agent). The oligonucleotide strand 1 labeled with fluorescein and the oligonucleotide strand 4 labeled with DABCYL were custom synthesized (Gibco-BRL
Life Technologies, Inc.).
The fluorescein and DABCYL Tabled oligonucleotides were annealed in a reaction, as described above, to generate synthetic Holliday Junction templates. The helicase reaction was performed as described above. The results of the helicase reaction were monitored by measuring the unquenching of the Holliday Junction templates with time (Figure 11).
The helicase assay using Holliday Junction templates labeled with fluorescent-quenching agents can be adapted for use in high throughput analyses to test 2GFE 39, 2CFE 21, and other polypeptides for their ability to resolve 'the templates into duplex structures.

The following provides a description of the methods used to characterize purified, CFE 8 polypeptide, which lacks a histidine tag. The CFE 8 is a putative DNA single-stranded binding protein.
Computer-Aided Comparison The computer-aided comparison, as described in Example 9 supra, suggests that the CFE
8 polypeptide (SEQ ID N0:121) may be a single stand binding protein homologue, such as SSB.

Size Exclusion Chromatography The 2CFE 8 polypeptide (SEQ ID N0:339) was characterized by size exclusion chromatography, using the Biosil SEC-125 HPLC Gel Filtration column as described in Example 8 supra. The chromatogram showed one peak corresponding to a molecular weight of approximately 89 lcDa. Based on the nucleotide sequence, the predicted molecular weight of 2CFE 8 is 17,351 Da. In non-denaturing conditions, 2CFE 8 forms a multimer.
Binding~lReaction The 2CFE 8 polypeptide was reacted with a single-stranded oligonucleotide A.
Briefly, the binding reaction included: 50 ~,M of 2CFE 8 polypeptide, 50 ~.M oligo strand A, 20 mM Tris/20 mM ICI pH 7.5. The binding reaction was performed at 37 degrees C, for 2 hours.
Oligonucleotide strand A:
5'-TTAGGGCCCGGGCTATCTTACAATCTCGTT-3' (SEQ ID N0:442) Capillary Electrophoresis The results of the binding reaction was monitored by capillary electrophoresis, following the methods described in "Handbook of Capillary Electrophoresis" 2°a Edition, 1997, ed.
J. Larders.
Separation was performed using an uncoated capillary tube (360 ~,m o.d., 50 ~,m i.d., with a 50 cm effective separation length; Watrex International, Inc., Pittsford, NY) and 50 mM borate pH 9.3 as the mobile phase, at 25 lcVolts, 20 minutes separation time.
The results indicate that 2CFE 8 alone elutes as a sharp peak, indicating little adsorption to the uncoated capillary wall (Figure 12 A). The shape of the peak and peak retention time changed with 2CFE 8 in the presence of all oligonucleotides tested (Figure 12 B).
As a negative control, MurB polypeptide (Pucci, M. J., L. F. Discotto, and T.
J.
Dougherty 1992 "Cloning and Identification of the Escherichia coli murB DNA
sequence, which encodes UDP-N-acetylenolpyruvoylglucosamine reductase" J.
Bacte~iol.174:1690-'1693) was reacted with the same oligonucleotides. MurB
reacted with or with out the oligonucleotides showed no change in peak shape or retention time.
After capillary electrophoresis analyses, the 2CFE8 alone and 2CFE,plus oligonucleotide samples were run on native polyacrylamide gels to determine whether the polypeptide was intact. The results indicate that in all cases, 2CFE 8 was intact and had not degraded with time or storage.
Mobility Shift Assa, The ability of 2CFE 8 polypeptide to bind oligonucleotide strand A was tested in a mobility shift assay.
The results indicate that 2CFE 8 binds single stranded oligonucleotides (Figure 13 A and B). In Figure 13 A, the gel was stained with ethidium bromide. The unbound oligonucleotides appear near the bottom of the gel, while the bound oligonucleotides appear near the middle. The same gel was stained with Coomassie (Figure 13 B), revealing that 2CFE 8 polypeptide bound .to the oligonucleotide migrated further than unbound 2CFE 8, due to the change in charge carried by the oligonucleotide.
Various ratios of 2CFE8:oligo were tested. The optimal binding ratio was 2:1.
The Effect of M~Ch The 2CFE 8 polypeptide precipitated in the presence of 5 mM MgCla. The precipitation was reversible by the addition of 1 ~.M of the oligonucleotides tested. The observation indicates specific binding between 2CFE 8 polypeptide and the oligonucleotides tested.

Scintillation Proximi Assay Scintillation proximity. assay (SPA) methods can be used in a high throughput screening procedure to monitor, for example, a binding reaction. SPA utilizes beads (Amersham) which are coated on the surface with a particular compound or molecule. For example, the SPA bead may be coated with avidin to facilitate binding with any molecule having a biotin tag.
The binding reaction of the 2CFE 8 polypeptide and the oligonucleotide strand A can be monitored using SPA beads and a scintillation counter. The beads can be coated with avidin, the 2CFE 8 polypeptide can be tagged with biotin, and the oligonucleotide strand A can be radiolabeled.

The, following provides a description of the methods used to characterize purified, 2CFE
3 (SEQ ID N0:334) and 2CFE 86 (SEQ ID N0:409) polypeptides.
The 2CFE 3 polypeptide catalyzes the conversion of D-glucosamine-6-phosphate to D-glucosamine-1-phosphate, indicating that 2CFE 3 mediates amino-sugar biosynthesis through the N-acetyl glucosamine pathway (Figure 14).
The 2CFE 86 polypeptide catalyzes the conversion of D-glucosamine-1-phosphate to N-acetylglucosamine-1-phosphate, and the conversion of N-acetylglucosamine-1-phosphate to UDP-N-acetylglucosamine-1-phosphate, which indicates that 2CFE 86 also mediates amino-sugar biosynthesis through the N-acetyl glucosamine pathway (Figure 14).
Computer-Aided Comparisons Of CFE 3 The computer-aided comparison, as described in Example 9 supra, suggested that the CFE 3 polypeptide (SEQ ID N0:116) is a phosphoglucosamine mutase, such as GImM.

Purification of the CFE 3 Polypeptide The 2CFE 3 polypeptide was produced using the large scale IPTG-induced method described in Example 5, supra. The 2CFE 3 polypeptide lacks a C-terminal histidine tag.
The 2CFE 3 polypeptide was ,purified using a 2-column procedure. The 2CFE 3 polypeptide preparation was eluted from a 26/10 Q Sepharose column (Pharmacia) using a 0-1.0 M NaCI gradient, 2 ml/minute flow rate, and the gradient size was 1 liter. Then the 2CFE 3 polypeptide was eluted from a hydroxyapatite Bio-gel column (Bio-Rad) using a 5-200 mM potassium phosphate (pH 8.0) gradient, the flow rate was 0.3 ml/minute, and the gradient size was 300 ml. A sample of the 2CFE 3 preparation was electrophoresed on an SDS polyacrylamide gel (Figure 4).
Affinity Capillary Electrophoresis of CFE 3 Affinity capillary electrophoresis methods were used to determine whether the polypeptide binds to various glucose derivatives. Binding was performed under equilibrium conditions, in which the sugars were dissolved in the running buffer and reacts with 2CFE 3 during separation in the column. The affinity capillary electrophoresis method used to analyze 2CFE 3 follows the methods described in "Handbook of Capillary Electrophoresis" 2°d Edition, 1997, ed. J.
Landers.
Briefly, 2CFE 3 polypeptide was reacted with increasing amounts of various glucose derivatives (e.g., substrate) at 25, 30 and 37 degrees C. .The glucose derivatives included UDP-glucose, glucose-1-phosphate, glucose-6-phosphate, glucosamine-1-phosphate, and glucosamine-6-phosphate. The reaction included: 2CFE 3 polypeptide (2.0 mg/ml), separation buffer (25 mM Tris; 192 mM Glycine, pH 8.0; BupH Tris-Glycine Buffer Packs, Pierce). Separation was performed at 25 kVolts, separation time was 15 or 20 minutes.
The results shown in Figure 15 A indicate that at 25 degrees C, 2CFE 3 binds to D-glucose-1-phosphate in a dose-dependent manner, as the peak shape and/or the retention time for 2CFE 3 changes in the presence of 100 and 500 ~.M D-glucose-1-phosphate compared to unreacted 2CFE 3.
The results shown in Figure 15 B indicate that at 25 degrees C, 2CFE 3 binds to D-glucosamine-6-phosphate in a dose-dependent manner, as the peak shape and/or the retention time for 2CFE 3 changes in the presence of 100 and 500 ~.M D-glucosamine-6-phosphate compared to unreacted 2CFE 3.
The results shown in Figure 15 C indicate that at 25 degrees C, the 2CFE 3 polypeptide also binds to glucose-6-phosphate.
A comparison of 2CFE 3 reacted with various glucose derivatives, at 30 degrees C, is shown in Figure 15 D. The results indicate that D-glucosamine-6-phosphate is a putative substrate for 2CFE 3, as this reaction exhibits the greatest change in peals shape and/or retention time.
CFE 3: Capillary Electrophoresis and Laser-Induced Fluorescence In a further analysis of 2CFE 3 polypeptide, capillary electrophoresis was performed with laser-induced fluorescence in order to separate and detect interaction between the substrate (e.g., D-glucosamine-6-phosphate) and the product (e.g., D-glucosamine-1-phosphate) in a one dose, one time-point procedure.
The 2CFE 3 polypeptide was derivitized by reacting 10 mM FITC (fluorescein isothiocyanate dissolved in methanol; Calbiochem, San Diego, CA) with D-glucosamine-6-phosphate, at ambient temperature, in the dark, overnight. The FITC-derivatized 2CFE
3 polypeptide (2.0 mg/ml) was reacted with the substrate (D-glucosamine-6-phosphate and D-glucosamine-1-phosphate) for one hour.
Separation was performed using an uncoated capillary (360 ~.m o.d., 50 ~m i.d., with a 50 cm effective separation length) and 50 mM borate (pH 9.3) as the mobile phase. The argon-ion laser had an excitation wavelength of 488 nm and an emission filter of 520 run (Beckman, Fullerton, CA). The results shown in Figure 16 indicate that 2CFE 3 binds and catalyzes the conversion of D-glucosamine-6-phosphate to D-glucosamine-1-phosphate.
Computer-Aided Comparison Of CFE 86 The comparison results, as described in Example 9 supra, suggested that the polypeptide (SEQ ID N0:195) is an acetyltransferase, such as GImU which is a bifunctional enzyme in E. coli. It has been previously shown that, in E coli, GImU is a bifunctional protein having both the acetyltransferase and uridylyltransferase active sites (Mengin-Lecreulx, D. and J. van Heijennort 1994 J. Bacte~iol. 176:5788-5795;
Gehring, Al., et al., 1996 Biochemistry 35:579-585). The bifunctional enzyme catalyzes the conversion of D-glucosamine-1-phosphate to N-acetylglucosamine-1-phosphate (acetyltransferase), and catalyzes the~conversion of N-acetylglucosamine-1-phosphate to UDP-N-acetylglucosmine-1-phosphate (uridylyltransferase). The Km of the acetyltransferase and uridylyltransferase reactions has been previously calculated (Mengin-Lecreulx, D. and J. van Heijennort 1994 supra ). Additionally, the crystal structure of GlmU from E. coli is known (Brown, K., et al., 1999 EMBO J.
18:4096-4107).
Purification of the CFE 86 Polyp~tide The 2CFE 86 polypeptide (SEQ ID N0:409) has a C-terminal histidine tag. The 86 polypeptide was produced using the large scale IPTG-induced method described in Example 5, supra. The 2CFE 86 polypeptide was purified using the Ni-NTA
affinity column method described in Example 6, supra. The eluted 2CFE 86 polypeptide was dialyzed against 50 mM Tris-Cl, 100 mM NaCI, 25% glycerol, pH 8Ø Samples of the purified 2CFE 86 polypeptide were electrophoresed on a polyacrylamide gel (Figure 17).

Coupling CFE 3 and CFE 86 to Produce UDPAG
A biochemical assay was performed, to determine whether 2CFE 3 and 2CFE 86 convert ' D-glucosamine-6-phosphate to UDP-N-acetylglucosamine-1-phosphate (e.g., UDPAG).
The 2CFE 3 and 2CFE 86 polypeptides were used in a coupled reaction based on the assays described in Jolly, L. P., et al., 1999 Eu~. J. Biochem. 262:202-210.
A time-dependent and dose-dependent assay were performed. Briefly, the assay was performed in 96-well plates, each well including 100 ~,1 volume. The assay included: 1 mM D-glucosamine-6-phosphate (Sigma); 0.7 mM D-glucosamine-1,6-diphosphate (Sigma); 1.2 mM acetyl-Coenzyme A (Sigma); and 5 mM uridine-5'-phosphate (Sigma);
3 mM MgCl2 (Sigma); 50 mM Tris-Cl, pH 8.0 (Life Technologies). The reaction was started by adding 1 ~.g of 2CFE 3; and 10 ~,g of 2CFE 86. The reaction was performed at room temperature. The reaction was stopped at 0, 15, 30, and 65 minutes, by filtering out the 2CFE polypeptides.
The results of the assay was monitored by HPLC (high pressure liquid chromatography) using an Optisil 10~, SAX column (250 x 4.6 mm), measuring at 262 nm, the mobile phase was 150 mM I~HHZP04 (pH 3.5), and 1.5 ml/minute flow rate. The results shown in Figure 18 show the time-dependent assay and indicate that HPLC detected the presence of UDPAG.
CFE 86: The Urid~yltransferase Reaction The 2CFE 86 polypeptide was tested in a uridylyltransferase reaction, in which N-acetyl-D-glucosamine-1-phosphate and' UTP produce UDP-N-acetylglucosamine. The uridylyltransferase reaction was monitored using a malachite green/inorganic pyrophosphatase assay (e.g., malachite green-IPPAse assay) and/or monitored using HPLC. The malachite green-IPPAse assay was used to measure orthophosphate production from digestion of the pyrophosphate liberated in the uridylyltransferase reaction.

The malachite green reagent was prepared as follows. A 0.045 % solution of malachite green (Sigma; M9636) was prepared in water. A 4.2 % solution of ammonium molybdate (Mallinckrodt) was prepared in 4N HCI. The malachite green and ammonium molybdate were mixed in a 3:1 ratio, and stirred for about 20 minutes. The mixture was filtered, and stored at 4 degrees C. The inorganic pyrophosphatase (Sigma; I-2267) was diluted to 0.1 U/~,l in 50 mM Tris/3mM MgCl2 ph 8.0, and stored at 4 degrees C.
The.uridylyltransferase reaction was performed in 96-well plates. The coupled reaction described herein was performed, in the presence of 2CFE 3 alone or 2CFE 3 and 86, and included the addition of 0.5 U/well of the diluted inorganic pyrophosphate. The reaction was mixed for 5 minutes at room temperature. The reaction was stopped by the addition of 240 ~,1/well of the malachite green reagent and 30 ~,1/well of 34%
sodium citrate, and the reaction was mixed. The results of the uridylyltransferase reaction was monitored by spectrophotometry at 660 nm.
The results of separate uridylyltransferase reactions were monitored by HPLC, using a Phenosphere-NEXT C18 column (250 x 4.6 mm). The mobile phases included A and B
as follows: A) methanol/10 mM potassium phosphate pH 6.5 (0:100); and B) methanol/10 mM potassium phosphate pH 6.5 (40:60). The mobile phases were run under the following conditions: 100% mobile phase A for 5 minutes,~to 100%
mobile phase B in 3 minutes; and hold 100% mobile phase B for 9 minutes. The retention time for the UDPAG product is approximately 5.75 to 6.0 minutes.
The results three uridylyltransferase reactions, monitored by HPLC are summarized in Table III below.

TABLE III
Specific Activity Purified CFE 86: (nmol/min/u,~):
2CFE 86-1 3.1 2CFE 86-2 3.4 2CFE 86-3 3.1 The results of the uridylyltransferase reactions, monitored by HPLC or HPLC
and Malachite Green IPPAse assays are summarized in Table IV below.
TABLE IV
Reaction: Km~~.,~.M ): Method:
Acetvltransferase reaction:

Glucosamine-1-P 150 HPLC
Acetyl-coA
Urid~ytransferase reaction:
N-acetylglucosamine-1-P 48 HPLC and MG/IPPAse The following provides a description of the methods used to characterize various 2CFE
polypeptides, including CFE 21, 34, 35, 39, and 90. The molecular weight of these 2CFE
polypeptides were analyzed by size exclusion chromatography and gel electrophoresis.
The 2CFE 34, 35, and 90 polypeptides putatively mediate fatty acid biosynthesis.

Computer-Aided Com arison The computer-aided comparison, as described in Example 9 supra, suggests that (SEQ ID N0:143), CFE 35 (SEQ ID N0:144), and 90 (SEQ .ID N0:199) are polypeptides which mediate a fatty acid biosynthesis pathway (Figure 19) The ,comparison suggests that CFE 34 is a malonyl CoA:ACP transcylase, which catalyzes the reaction in which malonyl CoA and acyl carrier protein (ACP) are converted to malonyl-ACP and CoA. Thus, the CFE 34 polypeptide may be a homologue of E coli FabD.
The comparison suggests that CFE 90 is a 3-oxoacyl-ACP synthase II (beta lcetoacyl-ACP synthase II) which catalyzes the reaction in which malonyl-ACP is converted to beta aceto acetyl-ACP. Thus, the CFE 90 polypeptide may be a homologue of E.
coli FabF.
The comparison suggests that CFE 35 is a 3-oxoacyl-ACP reductase (beta aceto acetyl ACP reductase) which catalyzes the reaction in which beta-lceto-acetyl-ACP is converted to beta-hydroxy-acetyl-ACP. Thus, the CFE 35 polypeptide may be a homologue of E.
coli FabG.
Size Exclusion Chromatogrraphy The estimated molecular weights of 2CFE 34 (SEQ ID N0:361), 2CFE 35 (SEQ ID
N0:362), and 2CFE 90 (SEQ ID N0:413) were determined using the Biosil SEC-125 HPLC Gel Filtration column as described in Example 8, sup~~a.
The results suggest that 2CFE 34 polypeptide is a monomeric protein (33,093 Da), 2CFE
is a trimeric protein (25,758 Da; approximately 85%), and 2CFE 90 is a dimeric 30 protein (43,930 Da). Selected eluted samples of 2CFE 34 were electrophoresed on a polyacrylamide gel (Figure 20).

Biochemical Assay: CFE 34 The function of 2CFE 34 was determined by performing various biochemical reactions.
To determine whether 2CFE 34 catalyzes the convertion of malonyl-CoA to malonyl and CoA, the following reaction was performed.
The biochemical reaction was performed in the presence of acyl carrier protein. The reaction included the following: 10 ~,M 14C labeled malonyl-CoA, 20 ~,M ACP, 30 ~,M
2CFE 34 (e.g., FabD) in 20 mM Tris-Cl, pH 8.0 and 5 mM DTT in 300 ~,1 volume.
The reaction was performed at room temperature (e.g., approximately 24 degrees C) for 30 minutes. The reaction was terminated with the addition of 45,1 of 0.5% TFA.
The labeled reaction was injected onto a MonoQ 5/5 column on a Gilson HPLC.
Detection was performed by monitoring the radioactivity of the continuous flow-through of the HPLC effluent. Chromatography was performed using a buffer gradient for column elution. Buffer A included 20 mM Tris-Cl, pH 8.3. Buffer B was the same as Buffer A
and included 1 M NaCI. The program was held at 90% A, 10% B for 10 minutes followed by a linear ramp to a final mix of 50% of each Buffer A and B over 10 minutes.
The substrate (e.g., 14C malonyl-CoA) eluted at 9.9 minutes, the product (e.g., 14C
malonyl-ACP) eluted at 14.3 minutes. The results indicate that CFE 34 catalyzes the conversion of malonyl-CoA and acyl carrier protein (ACP) to malonyl-ACP and CoA. .

The following provides a description of the methods used to characterize CFE
polypeptides 40, 41, and 46.

Computer-Aided Comparison The computer-aided comparison, as described in Example 9 supra, suggests that the CFE
40 polypeptide (SEQ ID N0:149) is a phosphomethylpyrimidine (HMP-P) kinase involved in thiamine biosynthesis.
The comparison, as described in Example 9 supra, suggests that the CFE 4.1 polypeptide (SEQ ID NO:150) has a GTP-binding motif and may be a protease.
The comparison, as described in Example 9 supra, suggests that the CFE 46 polypeptide (SEQ ID NO:155) has an ATP-binding motif.
Affinity Purification of CFE 41 The large-scale method described in Example 5 supra (e.g., IPTG-induced protein production) was used to prepare a sample of 2CFE 41 polypeptide (SEQ ID
N0:368).
The sample was affinity purified using the Ni-NTA method described in Example 6, supra. The eluted fractions were loaded onto and run on a 12% SDS-PAGE gel (Novex) (Figure 21).
Circular Dichroism and Circular Dichroism Thermal Melt Analysis Circular dichroism and circular dichroism thermal melt methods were performed using JASCO instrumentation. The concentration of the isolated 2CFE 40 (SEQ ID
N0:367) was approximately 21 ~.M, in a 0.1 cm pathlength cell at 210 nm. The circular dichroism spectrum suggests that this preparation of 2CFE 40 had mixed alpha and beta secondary structure. The circular dichroism thermal melt spectrum suggests that 2CFE
40 has a Tm 'of approximately 67 degrees C. The 2CFE 40 polypeptide precipitates at approximately the Tm.

The concentration of the isolated 2CFE 41 (SEQ ID N0:368) was approximately 70 ~.M, in a 0.02 cm pathlength cell. The circular dichroism spectrum suggests that this preparation of 2CFE 41 had mixed alpha and beta secondary structure, with a greater percentage of alpha structures. The circular dichroism thermal melt spectrum suggests that 2CFE 41 has a Tm of approximately 38 degrees C. The 2CFE 41 polypeptide precipitates at approximately the Tm.
The concentration of the isolated 2CFE 46 (SEQ ID N0:373) was approximately 23 ~.M, in a 0.1 cm pathlength cell at 280 nm. The circular dichroism spectrum suggests that this preparation of 2CFE 46 had mixed alpha and beta secondary structure. The circular dichroism thermal melt spectrum suggests that 2CFE 46 is highly stable at elevated temperatures. At 90 degrees C, the 2CFE 46 polypeptide exhibited only a 27%
loss in signal and the polypeptide remained soluble.
Capillary Electrophoresis Capillary electrophoresis was performed on samples of purified 2CFE 40, 41 and 46.
The electropherograms of 2CFE 40, 41, and 46 are shown in Figure 22.

The following provides a description of methods that can be used to characterize CEG
polypeptides (e:g., CFE polypeptides).
Computer-Aided Com~lation Computer-aided compilation of bacterial metabolic pathways may be analyzed using Pathway Tools from Doubletwist, based on the EcoCyc system (I~arp P.D., et al., 1999 .Nucleic Acicls Res. 1999 27(1):55-58). This analysis may be used to predict which CFEs mediate various steps of the pathways. This information may be used in combination with the results of a binding reaction which identifies a ligand or substrate that binds with a CFE polypeptide.
Identifying the Function of a CFE Polypeptide The function of a CFE polypeptide may be identified by identifying a ligand or substrate which binds with the CFE polypeptide. The ligand or substrate may be identified using fractionation and affinity capillary electrophoresis methods. The following method is based upon the assumption that the bacterial cell lysate includes the ligand or substrate.
A bacterial host cells carrying an endogenous (e.g. native) CFE gene or carrying a recombinant vector which includes a CFE gene may be cultured so that the CFE
polypeptide is produced by the cell. The cells may be ruptured in order to obtain the cell lysate. The cell lysate may be fractionated using HPLC technology. The HPLC
fractions may be reacted with a CFE polypeptide in a binding reaction, and the binding reaction may be analyzed by affinity capillary electrophoresis methods. The ligand or substrate which reacts with the CFE polypeptide may be identified using mass spectrophotometry methods (in "Mass Spectrometry" 1990 eds. McCloskey, J. A., in Methods in Euzymology volume 193; Henion, J., et al., 1993 "Mass Spectrometric Investigations of Drug-Receptor Interactions" Ther. Drug Mo~cit. 15:563-569; Loo, J. A., et al., "Application of Mass Spectrometry for Target Identification and Characterization" Med Res: Rev. 19:307-319; Nguyen, D. N., et al., 1995 "Protein Mass Spectometry:
Applications to Analytical Biotechnology J. Ch~omatog~.705:21-45).

The following provides a description of nuclear magnetic resonance (NMR) spectroscopy methods that were used to characterize CFE polypeptides.
High resolution NMR spectroscopy was applied to isN-fabled, l3C~isN-labeled, 2H~i3C~isN-labeled, and type-specifically isotopically labeled CFE polypeptide samples in the solution state for the following purposes: to assess various aspects of the structural state, e.g., foldedness, structural integrity; to refine a previously determined experimental structure of a close sequence homologue; to refine a homology-modeled structure; to assess the potential for a CFE polypeptide to bind small molecules; and to identify small-s , molecule pharmacophoric fragments that bind specifically to ' the CFE
polypeptide ("Nuclear Magnetic Resonance" 1994 eds. James, T. L. in Methods ih E~zzymology volume 239).
The NMR analysis includes screening both a compound deck of approximately 4,500 commercially available, structurally and chemically diverse compounds (the small-molecule pharmacophore deck) and a compound deck of proprietary, known, anti-microbial compounds (anti-microbial deck) against the CFE polypeptides (i.e., target polypeptides) to determine, either based upon perturbations to the chemical shifts of the amide proton and/or nitrogen resonances, as measured from a two-dimensional proton-nitrogen heteronuclear single-quantum correlation spectrum (2D screening method), or based upon increases in the linewidth of the compound's proton resonance(s), as measured by a one-dimensional TlP spin-lock difference spectrum (1D screening method), both whether a compound binds to a CFE polypeptide and, in the case of the 2D
screening method, where the compound binds on the CFE polypeptide.
Isotopic Labelin~~of CFE Polypeptides BL21-DE3 E. coli bacteria are transformed with the CFE expression vectors.
Expression takes place between 20°C and 37°C in minimal media containing [1sN]-ammonium sulfate as the sole nitrogen source and either glucose, [ZH]13-glucose, or [13C]6-glucose as the sole carbon source. Glucose is used for preparing uniformly 1sN-labeled and 2H/1sN-labeled CFE polypeptides. [aH]13-glucose is used for preparing type-specifically IH/13C-labeled, uniformly 1sN-labeled CFE polypeptides. [13C]6-glucose is used for preparing isC/isN-labeled CFE polypeptides. The minimal media is prepared in 100% H20 for expressing both uniformly ~sN-labeled and uniformly 13C/1sN-labeled CFE
polypeptides;
the minimal media is prepared in 95% D20 (deuterium oxide) and 5% H20 for expressing both type-specifically 1H113C-labeled, uniformly 15N-labeled. and just uniformly 2H/15N-labeled CFE polypeptides. In the case of type-specifically 1H/13C_labeled, uniformly 15N-Iabeled CFE polypeptides, 40 mg/L of protonated and uniformly l3CnsN-labeled isoleucine, valine and leucine amino acids are added to the minimal media.
NMR Screening Compounds in the anti-microbial deck are pre-dissolved to a target concentration of 16 mM in deuterated DMSO (dimethylsulfoxide) with each deck well containing only one compound. Compounds in the small-molecule, pharmacophore deck are pre-dissolved in deuterated dmso to a target concentration of 50 mM in groups of 8, i.e., each deck well contains 8 unique compounds with each compound at a target concentration of 50 mM.
3.5 ~,l of compound is placed at the bottom of a well in .a 96-well, screening plate. This well will be referred to as the compound screening well. Each compound screening well contains solution from only one deck well. 166.5 ~.1 of buffer is added to each compound screening well. 170 ~,l of a CFE polypeptide solution, initially at a concentration ranging from 200-300 ~,M, is added to each compound screening well; the contents of that well are then thoroughly mixed. The control screening well contains only 3.5 ~,1 of deuterated dmso. The screening plate is then centrifuged in a bucket rotor for 15 minutes at 3,500 rpm to insure that all particulate matter is at the bottom of the well.
The 2D screening method requires a single control screening well in which the compound solution consists only of deuterated DMSO. The 1D screening method requires a control screening well for each compound screening well. In the case of the 1D
screening method, the control screening well is prepared 'identically to the compound screening well except that the 170 ~,l of a CFE polypeptide solution is replaced by 170 ~,l of buffer.
The screening plate is covered with aluminum foil and placed onto a rack of a Gilson liquid handler. The Gilson liquid handler, under computer control by the NMR
host/data-acquisition software, is responsible for removing each sample from the screening plate, injecting the sample into a high-resolution, 1H/15N double-resonance NMR flow-probe, removing the sample from the flow-probe, and dispensing it back into the screening plate well from which the sample was originally removed. NMR data are. collected on the sample while the sample resides in the NMR flow-probe. The type of NMR data collected depends upon whether the 2D or 1D screening method is being used.
Determinin g Structural Characteristics of a CFE Polypeptide In assessing various aspects of the structural state of a CFE polypeptide, NMR
was used to provide the following information. The proton 1D spectra and proton-nitrogen 2D
correlation NMR spectra were used to assess the overall foldedness of a CFE
polypeptide without actually describing in detail that folded state. Unfolded and substantially misfolded proteins produced distinct signatures in these two types of NMR
spectra.
The chemical shift of most protein nuclei in either the set f HN, Ha, Hp, C', Ca, Cp, N} or the set {HN, C', Ca, Cp, N} for perdeuterated (e.g., aH-labeled) proteins were determined by procedures well known in the art that involve collecting up to 10 triple-resonance NMR data sets. The protein secondary structure was delineated as either helical, turn or extended (e.g., (3-sheet) by measuring ~(8oa - 8op), 08C', and ~~Ha where 8 refers to the chemical-shift value and 0 refers to the difference between chemical-shift values measured in this protein and those measured for the same residue type in a random-coil (unstructured), tetrameric peptide.
This secondary-structure profile was generated in approximately 2-3 weeks per protein.
The secondary-structure profile was used to confirm the functional identity of a protein.
It was also used to refine the list of possible functional identities of folds, predicted by various computational techniques including fold recognition which is associated with a protein or polypeptide.

NMR was used to generate folds of proteins or polypeptides for which both no structure was known of a sequence homologue and no structural homologue was discernible in the PDB by fold recognition techniques.
Refining a Structuxal Model Nuclear Overhauser (NOE) data were used to refine both homology-modeled structured and previously determined experimental structures of close sequence homologues. This process took approximately 2-3 weeks per structure.
The CFE 88 polypeptide was characterized by NMR analysis to establish its secondary structure. The NMR data was used to filter the computer-aided threading analysis. The NMR-determined secondary structure for CFE 88 suggested that CFE 88 is structurally similar to 4-aminoimidazole carboxylase.
The characteristics of other CFE polypeptides were analyzed by NMR methods. A
computer-aided threading analysis revealed that the N-terminal domain of the protein EGA, which both binds and hydrolyzes GTP, was both structurally similar and sufficiently similar in sequence to CFE 52 to suggest that CFE 52 had a similar function.
The NMR data of CFE 103 suggests that this polypeptide is unfolded. Circular dichroism spectra, as a function of temperature, also indicated that CFE103 was unfolded.
The CFEs 2, 42, 43, 68 and 88 polypeptides were tested for their ability to bind potential .25 inhibitor molecules by screening both the anti-microbial deck and the small-molecule, pharmacophore deck. CFE 34 was tested for its ability to bind potential inhibitor molecules by screening the anti-microbial deck.

Characterizing Small-Molecule Binding NMR-based screening was used to measure binding against both the small-molecule, pharmacophore deck and the anti-microbial deck. Binding data from these screens allowed assessment of the propensity of a protein to bind small molecules. The binding data was also used to identify sites on the protein which are capable of binding small molecules. The binding data was also used to identify common pharmacophores among the compounds which bind.
Reverse screening refers to a process whereby known anti-microbial compounds, the microbial target of which is unknown, are screened by a general method, e.g., binding as assessed by NMR, to find a physical interaction with polypeptide targets previously determined to be essential to the bacteria (i.e., the CFEs). The reverse screening method was used to determine which CFE polypeptides bind to which compounds in the anti-microbial deck. The reverse screening method included the following. The compounds in a proprietary compound deck were screened for Minimal Inhibitory Concentration (e.g., MIC). The compounds exhibiting antimicrobial activity were designated active compounds. The CFE polypeptides were screened to determine which polypeptide bind to which active compounds. The CFE polypeptides which bound to the active compounds) were confirmed, where possible, i.e., in cases where ~an in-vitro assay was possible to construct, as being inhibited in their function as a polypeptide by the active compounds) by examination of the inhibition profile of the compounds) against the CFE polypeptides. For additional confirmation, the effect of the compound on the microorganism harboring the CFE polypeptide was monitored (e.g., whole cell assays).
The structure of the active compound was used as a basis to generate chemically-related compounds by iterative synthesis. The chemically-related compounds were tested in a screening assay for binding with CFE polypeptides. The active compounds and the chemically-related compounds of interest were the compounds which exhibited an increase in binding affinity for a CFE polypeptide and/or exhibited drug-like properties.

The results of the reverse screening are as follows. 127 compounds from the proprietary compound deck exhibited anti-microbial activity. 94 of these active compounds were selected based upon both lack of cytotoxicity and lack of excessive hydrophobicity.
These 94 compounds were soluble to 16 mM in deuterated DMSO; these compounds were also deemed to be sufficiently soluble in aqueous buffer for both the 2D
and 1 D
NMR screening methods.
This subset of 94 compounds was used in an NMR-based screen to determine which compound binds to which CFE polypeptide. The CFE 42 polypeptide bound two different compounds with Ka's in the range of 0.2 to 1 mM; the CFE 43 polypeptide bound one compound with Kd ~ 30-50 ~,M; the CFE 34 polypeptide bound 13 compounds, one of which inhibited the polypeptide function with ICSO < 10 ~.M.
The enzyme assay used to confirm the NMR results which suggested CFE 34 interaction with the compounds included the following: 10 ~,M 14C-labeled malonyl CoA; 20 p,M
ACP, 30 pM CFE 34; 20 mM Tris-Cl, pH 8.0; 5 mM DTT; in the presence of absence of 50 ~.M of a compound solubilized at 40 mM in 100% DMSO and dilute 100-fold into 10% DMSO and further diluted 8-fold for a final concentration of 50 ~,M in 1.25%
DMSO. The reaction was performed at room temperature, the reaction was stopped with the addition of TFA. Two hundred ~.1 of the reaction was injected onto a Mono column. The chromatography conditions included: A) 20 mM Tris-Cl, pH 8.3; B) mM Tris-Cl, pH 8.3, 1 M NaCI. Hold 10% B for 5 minutes, linear gradient from 10% B
to 50%B in 10 minutes, back to 10% B in 1 minute, hold for 14 minutes to re-equilibrate.
The reaction substrate (14C- malonyl CoA) eluted at 9.9 minutes, the reaction product (14C-malonyl ACP) eluted at 14.3 minutes.

SEQUENCE LISTING
<110> Dougherty, Thomas J.
Pucci, Michael J.
S Dougherty, Brian A.
Davison, Daniel B.
Bruccoleri, Robert E.
Thanassi, Jane A.
1O <120> NOVEL BACTERIAL GENES AND PROTEINS THAT ARE ESSENTIAL
FOR CELL VIABILITY AND THEIR USES
<130> 30436.44USU1 IS <140> Not yet known <141> 2000-12-30 <160> 226 20 <170> PatentIn Ver. 2.0 <210> 1 <211> 708 <212> DNA
ZS <213> Streptococcus pneumoniae <400> 1 atgatttatg caggaattct tgccggtgga actggcacac gcatgggaat cagtaacttg 60 ccaaaacaat,ttttagagct aggtgatcga cctattttga ttcatacaat tgaaaaattt 120 30 gtcttggaac caagtattga aaaaattgta gttggggttc atggagactg ggttttacat 180 gcagaagatc ttgtagataa atatcttcct cttcataagg aacgtattat cattacaaag 240 ggtggtgctg accgcaatac aagtattgag aacatcattg aagccattga tgcttatcgc 300 ccgcttactc cagaggatat cgttgttacc cacgattctg ttcgtccatt tattacgctt 360 cgcatgattc aagacagtat caaacttgct caaaatcatg acgcagtgga tacagtagta 420 3S gaagcagtgg atactatcgt tgaaagtacc aatggtcaat tcattacagg tattccaaat 480 cgtgctcacc tctatcaggg acaaacacct caaacattcc gttgcaagga cttcatggac 540 ctttatggat ctctttctga tgaagagaag gaaatcttga cagatgcatg taaaatcttt 600 gtgatcaaag gaaaagatgt agccttggcc aaaggcgaat actcaaatct gaagattaca 660 accgtaacag atttgaagat tgcaaaaagt atgattgaga aagactag 708 <210> 2 <211> 558 <212> DNA
<213> Streptococcus pneumoniae <400> 2 atggctaacg taattattga aaaagctaaa gagagaatga cccagtctca ccaatcactt 60 gctcgtgaat ttggtggtat ccgtgctggt cgtgccaatg caagcttgct tgaccgtgta 120 catgtagaat actatggagt cgaaactcct cttaaccaaa tcgcttcaat tacgattcca 180 SO gaagcgcgtg ttttgttggt aacaccattt gacaagtctt cattgaaaga catcgaacgt 240 gccttgaacg cttctgatct tggtatcaca ccggctaatg acggttctgt gattcgcttg 300 gttatcccag ctcttacaga agaaactcgt cgtgaccttg ctaaagaagt gaagaaggtc 360 ggcgaaaatg ctaaagtggc tgtccgcaat atccgtcgcg atgctatgga cgaagctaag 420 aaacaagaaa aagcacaaga aatcactgaa gacgaattga agactcttga aaaagatatt 480 SS caaaaagtaa cagacgatgc tgttaaacac atcgacgaca tgactgctaa caaagagaaa 540 gaacttttgg aagtctaa - 558 <210> 3 <2l1> 1353 <212> DNA
<213> Streptococcus pneumoniae S
<400> 3 atgggtaaatattttgggactgatggagtccgtggagaagctaacctagaactaacacca60 gaattagcctttaaactaggacgttttggaggctatgttcttagtcaacatgaaacggaa120 gcgccgaaagtctttgtaggacgtgacacacgtatttcaggggaaatgctggaatcggcc180 ttggtggcaggtctcctttcagtagggattcacgtatacaaacttggtgtccttgcaaca240 ccagcagtagcttacttggttgaaactgaaggagcaagtgccggtgtcatgatttctgct300 agccacaacccagcccttgataacggaatcaagttctttggcggtgatggcttcaaacta360 gatgatgaaaaagaagcagaaattgaagccttgctagatgctgaggaagacactcttcct420 cgtccaagtgcagaaggcttaggaattttggtagattatccagaaggcttgcgtaagtat480 gaaggataccgtgtgtcaactggaactcctcttgatggaatgaaggttgccttggataca540 gctaatggagcagcttctaccagtgcccgtcaaatctttgcagaccttggtgcccaattg600 acggttatcggggaaacaccagacggtcttaacatcaaccttaatgttggttcaacacat660 ccagaagcccttcaagaagtggtcaaagaaagtgggtcagctattggtttggcctttgat720 ggagacagtgaccgcttgattgctgttgatgagaatggtgacatcgtcgatggtgacaag780 0 attatgtacatcatcggaaaatacctttctgaaaaaggacaattggctcaaaatacaatt840 gtgacaactgttatgtctaaccttggtttccacaaggccttgaatcgcgaaggtattaac900 aaggcagttactgcagttggtgaccgctacgttgttgaagaaatgagaaaatcaggctac960 aaccttggtggtgaacagtctggtcacgttatcttgatggattacaataccacaggtgat1020 ggtcaattatcagcagttcaattgactaaaatcatgaaggaaactggtaagagcttatca1080 gagttggcggcagaagtaacgatttatccacaaaaattagttaatatccgagtggaaaac1140 gtcatgaaggaaaaggccatggaagtgccagctatcaaggccatcatcgagaagatggaa1200 gaagaaatggcggggaacggccgtatccttgttcgtccaagtggaacagagcccctcttg1260 cgtgttatggcagaagcgcctacaacagaagaagtggactactatgttgataccatcaca1320 gatgtagttcgtgctgaaattgggattgactaa 1353 <210> 4 <211> 705 <212> DNA
<213> Streptococcus pneumoniae <400> 4 atgaaaaaaa tactaattgt agatgatgag aaaccaatct cggatattat caagtttaat 60 atgaccaagg aaggttatga agttgtaact gcttttaatg gtcgtgaagc gctagagcaa 120 tttgaagcag agcaaccaga tattattatt ctggatttga tgcttccaga aattgatggt 180 ttagaagttg ctaagaccat tcgtaagaca agcagtgtgc ccattcttat gctttcagcc 240 aaagatagtg aatttgataa ggttatcggt ttggaacttg gggcagatga ctatgtaacg 300 aaacccttct ccaatcgtga gttgcaggcg cgtgttaaag ctcttctgcg tcgttctcaa 360 cctatgccag tagatggtca ggaagcagat agtaaacctc aacctatcca aattggggat 420 ttagaaattg ttccagacgc ctacgtggct aaaaaatatg gcgaagaact agacttaacc 480 catcgtgaat ttgagctttt gtatcattta gcatcgcata caggtcaagt catcacgcgc 540 gaacacttgc ttgagactgt ctggggttat gactattttg gtgatgtccg cacagttgat 600 gtgactgtac gacgtctgcg tgagaagatt gaagatacgc ccagccgacc agagtatatc 660 ttgacgcgcc gtggtgtagg gtattacatg agaaataatg cttga 705 <210> 5 <211> 1107 <212> DNA
<213> Streptococcus pneumoniae <400> 5 atggaagaaa ttctctgtat tggttgtgga gcaaccattc agacgacaga taaagctggt 60 cttggtttta ccccccagtc ggcacttgaa aaaggtttgg agactggcga agtctattgc 120 caacgctgtt tccgtctccg ccactacaat gaaatcacag atgtccagtt gacgaacgat 180 gatttcctca agctcttgca cgaggtggga gacagtgatg ctttagtggt caatgtcatt 240 gatatctttg attttaatgg atctgtcatc ccaggtttac cacgtttcgt ctcgggcaat 300 gatgtcctct tggtaggaaa taaaaaagat atccttccta agtcagttaa gtctggtaag 360 attagccagt ggctcatgaa acgtgcccat gaagaaggtc ttcgtccagt cgatgtggtc 420 ctaacttcag cacaaaataa acatgccatt aaggaagtca ttgacaagat tgaacactac 480 cgtaagggcc gcgatgtcta tgtggtcggt gtgaccaacg ttggaaaatc aactctaatc 540 aatgctatta tccaagaaat cacgggtgat cagaatgtca tcactacttc acgcttccca 600 gggacaacct tggacaaaat agagattccg cttgacgacg gatcttatat ttacgatacg 660 l~ ccgggaatta tccaccgcca ccagatggct cactacttga cggccaaaaa cctcaagtat 720 gtcagtccta aaaaggaaat caagcctaag acctatcagc ttaatcctga gcaaacccta 780 tttttaggtg gtttgggacg ctttgacttt atagcaggag aaaagcaagg atttactgct 840 ttctttgata atgaactcaa actccatcgt agcaagcttg aaggagctag tgctttctac 900 gataagcacc tgggaactct tctgacacca ccaaatagca aggaaaaaga agatttccca 960 1S aggctagtcc agcatgtctt taccattaaa gataagacag acctagtcat ctcaggccta 1020 ggatggattc gtgtaacagg cacagcaaaa gtcgccgtct gggcaccaga aggcgtcgcc 1080 gtcgtcacac gaaaagcaat tatttaa 1107 <210> 6 ~ <211> 1461 <212> DNA
<213> Streptococcus pneumoniae <400> 6 2S atgtatccagatgatagtttgacattgcacacggacttgtaccagatcaacatgatgcag60 gtttactttgaccaagggattcacaataagaaggcggtctttgaggtgtatttccgccaa120 cagccttttaagaacggctatgcggtttttgcaggtttggaaagaattgtgaactatctt180 gaagacttgcgtttttcagatagtgatatagcctatttggagtcgcttggttatcatggg240 gcgttcttggattaccttcgcaatttcaagttggagttgaccgttcgttctgcccaagaa300 30 ggggatttggtttttgctaatgaaccgattgtgcaggtggaaggacctctagcccaatgt360 cagttggtcgaaacggctcttttgaacatcgtcaactaccagaccttggtggcgacgaag420 gcagctcgtattcgttcggttatcgaagatgaacccttgatggagtttgggacacgtcgg480 gctcaagaaacggatgcggccatctggggaacacgcgcagcggtgattggtggcgccaat540 ggaaccagcaacgtgcgtgcgggtaagotctttgacattcctgttttgggaacccatgcc600 35 catgccttggtacaggtttatggcaatgactatgaggctttcaaggcttacgctgcgacc660 cacaaaaattgtgtctttcttgtggatacctatgatacccttcgcatcggtgtaccagct720 gccattcaggtggcgcgtgagctgggtgatcagattaactttatgggtgtgcggattgac780 tctggggatattgcctacatttctaagaaagtccgtcagcaactggacgaggctggattt840 acagaggctaagatttatgcttctaatgatttggacgaaaatactatcctcaatctcaag900 ~ atgcaaaaggccaagattgatgtctggggtgtgggtaccaagctgattacagcctatgac960 cagccggctcttggggcggtttacaagattgttgcaatcgaagatgaaactggtcagatg1020 cgcaatacgattaagctgtctaataatgcggaaaaagtgtcgacgccaggtaagaagcag1080 gtgtggcgcattaccagtcgtgaaaaaggtaagtcagaaggtgattacatcacttatgat1140 ggtgtggatattagcgacatgacagaaatcaagatgttccatccgacctatacatacatc1200 4$ aagaagacggttcgtaattttgatgccgttcctctcttggtggatatcttcaaagaagga1260 atattagtttacaacttgcctagtttgactgacattcaggattatgcccgtaaagaattt1320 gacaagttgtgggatgagtataagcgtgtgctcaatccgcagcactatccagtggatttg1380 gcgcgtgatgtatggcaagataagatggacttgattgataagatgcgcaaggaagccctt1440 ggtgaaggagaagaagaatga , 1461 <210> 7 <211> 852 <212> DNA
<213> Streptococcus pneumoniae SS
<400> 7 ' atggctacta ttcaatggtt tcctggtcac atgtctaaag ctcgtcgaca ggtgcaggag 60 aatttaaaat ttgttgattt tgtgacgatt ttagtagatg cacgcttgcc tctatctagt 120 caaaatccta tgttgaccaa gattgttggt gataaaccaa aactcttgat tttaaacaag 180 gccgacttgg ctgatccagc aatgaccaag gaatggcgtc agtattttga atcacaagga 240 atccagacgc tagctatcaa ctccaaagag caagtgactg taaaagttgt aacagatgcg 300 gccaagaagc tcatggctga taagattgct cgccagaaag aacgtgggat tcagattgaa 360 accttgcgta ctatgattat cgggattcca aacgctggta aatcaactct gatgaaccgt 420 ttggctggta aaaagattgc tgttgttgga aacaagccag gggtcacaaa aggtcaacaa 480 tggcttaaaa ccaataaaga cctggaaatc ttggatacac cggggattct ctggcctaag 540 tttgaggatg aaactgttgc acttaagttg gcattgactg gagctatcaa ggatcagttg 600 cttcctatgg atgaggttac catttttggt atcaattatt tcaaagaaca ttatccagaa 660 aagctggctg aacgcttcaa acaaatgaaa attgaagaag aaccgtctgt gattattatg 720 gatatgaccc gcgccctcgg tttccgtgat gactatgacc gtttttacag tctcttcgtg 780 aaggaagttc gtgatggcaa actcggtaac tataccttag atacattgga agacctcgat 840 ggcaacgatt as 852 <210> 8 <211> 471 <212> DNA
<213> Streptococcus pneumoniae <400> 8 atgattaaca atgttgtact tgtagggcgt atgacacgtg acgctgagtt gcgttatacc 60 ccatcaaatg tagcagttgc gacttttact cttgcagtaa accgtacatt taagagtcaa 120 aatggtgaac gtgaggctga ttttatcaat gtcgttatgt ggcgccaaca ggctgaaaat 180 cttgctaact gggctaaaaa aggctcactt atcggggtga caggtcgtat ccagactcgt~240 agttacgata accagcaagg acaacgtgtc tacgtgacag aggtcgtggc tgagaatttc 300 caaatgttgg aaagccgtag tgtgcgtgag ggccacacag fitggagctta ctctgcacca 360 actgcaaact attcagcacc tacaaattca gtaccagact tttcacgtaa tgaaaatcca 420 tttggagcaa caaacccatt ggatatttca gatgatgatt taccattcta a 471 <210> 9 <211> 975 <212> DNA
<213> Streptococcus pneumoniae <400> 9 atgaaaacgc gtattacaga attattgaag attgattatc ctattttcca aggagggatg 60 gcctgggttg ctgatggtga tttggcaggg gctgtttcca aggctggagg attaggaatt 120 atcggtgggg gaaatgcccc gaaagaagtt gtcaaggcca atattgata.a aatcaaatca 180 ttgactgata aaccctttgg ggtcaacatc atgctcttat ctccctttgt ggaagatatc 240 gtggatctcg ttattgaaga aggtgttaaa gttgtcacaa caggagcagg aaatccaagc 300 aagtatatgg aacgtttcca tgaagctggg ataatcgtta ttcctgttgt tcctagtgtc 360 gctttagcta aacgcatgga aaaaatcggt gcagacgctg ttattgcaga aggaatggaa 420 gctggggggc atatcggtaa attaacaacc atgaccttgg tgcgacaggt agccacagct 480 atatctattc ctgttattgc tgcaggagga attgcggatg gtgaaggtgc tgcggctggc 540 tttatgctag gtgcagaggc tgtacaggtg gggacacggt ttgtagttgc aaaagagtcg 600 aatgcccatc caaactacaa ggagaaaatt ttaaaagcaa gggatattga cactacgatt 660 tcagctcagc actttggtca tgctgttcgt gctattaaaa atcagttgac tagagatttt 720 gaactggctg aaaaagatgc ctttaagcag gaagatcctg atttagaaat ctttgaacaa 780 atgggagcag gtgcccta.gc caaagcagtt gttcacggtg atgtggaggg tggctctgtc 840 atggcaggtc aaatcgcagg gcttgtttct aaagaagaaa cagctgaaga-aatcctaaaa 900 gatttgtatt acggagccgc taagaaaatt caagaagaag cctctcgctg gacaggagtt 960 gtaagaaatg actaa 975 SS <210> 10 <211> 423 <212> DNA
4.

<213> Streptococcus pneumoniae <400> 10 atgatcgata ttcaaggaat caaagaagcc cttccccacc gttatcctat gcttctagtg 60 gaccgtgtct tggaggtgag cgaggatacc attgttgcta tcaaaaatgt gaccatcaac 120 gagcctttct ttaacggcca ctttcctcaa tacccagtta tgccaggtgt tctgattatg 180 gaagccttgg cgcaaactgc cggtgtgttg gagttatcaa aacctgaaaa taaaggaaaa 240 ctggtctttt acgctggtat ggataaggtt aagttcaaga agcaagttgt accaggcgac 300 caattggtta tgacagcgac~ttttgtaaaa cgtcgtggca ccatagctgt ggttgaagca 360 l~ aaggctgaag tggatggcaa gcttgcagcc agtggtaccc ttacttttgc aattgggaac 420 taa 423 <210> 11 <211> 1023 ]$ <212> DNA
<213> Streptococcus pneumoniae <400> 11 atgattaatcaaatttatcaactaactaaacctaagtttatcaatgtcaaatatcaggaa60 ~ gaggctattgaccaagagaatcatatccttatccgtcccaactacatggctgtctgtcat120 gcggatcagcgttactaccagggaaaacgtgatcccaagattttgaataaaaagcttcca180 atggcaatgattcacgagtcatgtggaatcgtcatttctgaoccgagcggaacctacgag240 gttggtcaaaaagttgtcatgattcccaatcagtctcctatgcagagtgatgaagaattc300 tatgaaaactacatgacaggga,cccatttcttgtctagtggatttgatggctttatgaga360 2S gagtttgtttctctccctaaagatcgtgtggtggcttatgatgctattgaagatacggtt420 gcagccattacagagtttgtcagtgtgggcatgcacgctatgaatcgtctattgactctt480 gctcatagcaagcgggagcggatccccgttattggagatggaagtttagcttttgtggtt540 gccaatattatcaactatactttgccagaagcagagattgtggttattggtcgtcattgg600 gaaaagttggaactcttctcatttgccaaagaatgctatattacggataatattcctgaa660 30 gagttggcctttgaccatgcttttgaatgttgtggtggtgatggtactggaccagctatt720 aatgacttgattcgctacattcgtcctcagggaacaattctcatgatgggagttagcgaa780 tataaagtcaatctcaatactcgcgatgccttagaaaagggcttgctcttggttgggtca840 tctcgttctggtcgcattgattttgaaaatgctatccaaatgatgaaagtcaagaaattt900 gccaatcgtcttaaaaatatcctttatctagaagaacctgtaagagaaattaaagatatt960.

35 caccgtgtctttgcaaccgatttaaacacagcctttaaaacagtgtttaagtgggaagta1020 taa 1023 <210> 12 <211> 1344 40 <212> DNA
<213> Streptococcus pneumoniae <400> 12 atgaacttaa aaactacttt gggccttctt gctggacgtt cttcccactt cgttttaagc 60 45 cgtcttggac gtggaagtac gctcccaggg aaagtcgccc ttcaatttga taaagatatt 120 ttacaaaacc tagctaagaa ctacgagatt gtcgttgtca ctggaacaaa tggaaaaacc 180 ctgacaactg ccctcactgt cggcatttta aaagaggtct atggtcaagt tctaaccaat 240 ccaagcggtg ccaacatgat tacagggatt gcaacaacct tcctaacagc caaatcttct 300 aaaactggga aaaatattgc cgtcctcgaa attgacgaag ccagtctatc tcgtatctgt 360 50 gactatatcc agcctagtct ttttgtcatt actaatatct tccgtgacca gatggaccgt 420 ttcggtgaaa tctatactac ctataacatg atattggatg ccattcggaa agttccaact 480 gctactgttc tccttaacgg agacagtcca cttttctaca agccaactat tccaaaccct 540 atagagtatt ttggttttga cttggaaaaa ggaccagccc aactggctca ctacaatacc 600 gaagggattc tctgtcctga ctgccaaggc atcctcaaat atgagcataa tacctatgca 660 SS aacttgggtg cctatatctg tgagggttgt ggatgtaaac gtcctgatct cgactatcgt 720 ttgacaaaac tggttgagtt gaccaacaat cgctctcgct ttgtcataga cggccaagaa 780 tacggtatcc aaatcggcgg gctctataat atctataacg ccctagctgc tgtggccatc 840 gcccgtttcc tcggcgcaga ttcccaactc atcaaacagg gatttgacaa gagccgtgct 900 gtctttggac gccaagaaac ctttcatatc ggtgacaagg aatgtaccct tgtcttgatt 960 aaaaatccag tcggtgcaac ccaagctatc gaaatgatca aactagcacc ttatccattt 1020 agcctatctg tcctccttaa tgccaactat gcagatggaa ttgacactag ctggatct.gg 1080 gatgcagact ttgagcaaat cactgacatg gacattcctg aaatcaacgc tggcggtgtt 1140 . cgtcattctg aaatcgctcg tcgcctccga gtgactggct atccagctga gaaaatcact 1200 gaaacgagta atctggagca agttctcaag accattgaga atcaagactg caagcatgcc 1260 tatattctgg caacttatac tgccatgctg gaatttcgtg aactgctggc tagtcgtcag 1320 attgttagaa aggagatgaa ctaa 1344 <210> 13 <211> 783 <212> DNA
<213> Streptococcus pneumoniae <400> 13 atggtttata cttcactttc ctcaaaagat ggcaattacc cctatcagct caacattgcc 60 .cacctctacg gaaatctcat gaatacctac ggggacaatg gaaacatcct catgctcaag 120 tatgtggctg aaaaactggg agcccatgtg accgttgaca tcgtttctct ccatgatgac 180 0 tttgatgaaa atcactacga catcgccttt ttcggtggtg gtcaagactt tgaacaaagt 240 atcattgcag acgacctacc tgctaaaaaa gagagcattg acaactacat ccaaaacgac 300 ggtgtagttc tggctatctg cggtggtttc caactattgg gtcaatatta tgttgaagct 360 tcaggaaaac gtatcgaagg gctaggggtc atgggacact acacgctcaa ccagaccaat 420 aaccgtttta tcggtgacat caagattcac aatgaagatt tcgatgaaac ctactatgga 480 25 tttgaaaatc accaaggtcg taccttcctc tctgatgacc aaaaaccgct gggacaggtt 540 gtctatggaa atggaaacaa cgaagaaaag gtcggtgaag gggttcatta taagaatgtc 600 tttggttcct acttccacgg gcctatcctc tctcgtaatg ccaatctggc ttatcgccta 660 gttactactg ccctcaagaa gaaatatggt caggacatcc aactccctgc ctatgaggac 720 attctcagcc aagaaatcgc tgaagagtac agtgacgtca aaagcaaggc tgacttttct 780 30 taa 783 <210> 14 <211> 276 <212> DNA

35 <213> Streptococcus pneumoniae <400> 14 atggcaaacaaacaagatttgatcgctaaagtagcagaagctacagaattaactaagaaa60 gactcagcagcagcagttgaagctgtatttgcagcagtagctgactatcttgcagctggt120 40 gaaaaagttcagttgatcggttttagtaactttgaagttcgtgagcgcgcagaacgtaaa180 ggtcgcaacccacaaactggtaaagaaatgacaattgcagcttctaaagtaccagcattc240 aaagctggtaaagctcttaaagacgctgttaaataa 276 <210> 15 45 <211> 840 <212> DNA

<213> Streptococcus pneumoniae <400> 15 50 atgggaattgctctagaaaatgtgaattttacatatcaagaaggtactcccttagcttca60 gcagctttgtcggatgtttctttgacgattgaagatggctcttatacagctttaattggg120 cacacaggtagtggtaaatcaactattttacaactcttaaatggtttattggtgccaagt180 caagggagtgtgagggtttttgataccttaatcacctcgacttctaaaaataaagatatt240 cgtcaaattagaaaacaggttggcttggtatttcagtttgctgaaaatcagatttttgaa300 55 gaaacggttttgaaggacgttgcttttggaccgcaaaattttggagtttctgaagaagat360 gctgtgaagactgcgcgtgagaaactggctctggttggaattgatgaatcactttttgat420 cgtagtccgtttgagctgtcagggggacaaatgagacgtgttgccattgcaggcatactt480 gccatggagc cagctatatt agtcttagat gagccaacag ctggtctaga tcctctaggg 540 agaaaagagt tgatgaccct gttcaaaaaa ctccaccagt cagggatgac catcgtcttg 600 gtaacgcatt tgatggatga tgttgctgaa tatgcgaatc aagtctatgt aatggaaaag 660 ggacgtttag taaagggggg caaaccaagt gatgtctttc aagacgttgt ttttatggaa 720 gaagttcagt tgggagtacc taaaattacg gccttttgta aacgattggc tgatagaggc 780 gtgtcattta aacgattacc ggttaagata gaggagttca aggagtcgct aaatggatag 840 <210> 16 <211> 930 <212> DNA
<213> Streptococcus pneumoniae <400> 16 atggatattcaatttttaggaacgggggctggtcagccctctaaagcccgcaacgtttca60 IS agtctcgccctgaaacttttggatgagattaacgaagtttggctctttgactgtggagaa120 ggtacgcaaaatcgcattctggaaaccacaattcgaccacgtaaggtcagcaaaatcttt180 attacccatctgcatggagaccacatttttggtttgccaggtttcctttctagccgtgcc240 tttcaggccaatgaagagcagacagatttggaaatctacggacctcaaggaatcaagtca300 tttgtcttaaccagccttcgtgtgtcaggttctcgtctgccctaccgcattcatttccat360 gagtttgaccaagattctctaggtaaaattcttgaaatcgataaattcactgtgtatgca420 gaggagctggaccacactattttctgtgttggctatcgtgtcatgcaaaaggatctagaa480 gggacgctggatgctgaaaaactcaaggctgctggtgttccgttcggcccgctttttggt540 aaaatcaaaaatggccaggatcttgttttggaagacggaactgaaatcaaggcagcagac600 tatatctcagcgccacgtccaggtaagattatcactattttaggagacactcgaaaaacg660 2S gatgccagtgtgcgtctggctgtcaatgcagatgtcctagttcatgagtccacttatggc720 aagggtgatgaaaaaattgctcgtaaccatggtcactcaactaatatgcaagctgcacaa780 gtagcggtagaagcaggtgccaaacgcctcctactcaaccatatcagtgcccgtttcctc840 tcaaaagatattagcaaactcaagaaagacgctgccacaatttttgaaaatgtccatgtg900 gtcaaagacttggaagaagtggaaatctag 930 <210> 17 <211> 1662 <212> DNA
<213> Streptococcus pneumoniae <400> 17 atgagtaatatcagtttaacaacacttggtggtgtgcgtgagaatggaaaaaatatgtac60 attgctgaaattggagagtccatttttgttttgaatgtagggttaaaatatcctgaaaat120 gaacaattaggggtcgatgtggtgattccaaacatggattacctttttgaaaatagcgac180 0 cgtattgctggggttttcttgacccacgggcatgcggatgcgattggtgctctaccttat240 ctcttggcagaggctaaagttcctgtatttgggtctgagttgaccattgagttggcaaag300 ctctttgtcaaa.ggaaatgatgccgttaagaaatttaatgatttccatgtcattgatgag360 aatacggagattgattttggtgggacagtggtttccttcttccctacgacttactccgtt420 ccagagagtctgggaattgtcttgaagacatcggaaggaagcatcgtttatacaggtgac480 ttcaaatttgaccaaacggctagtgaatcttatgcaactgattttgctcgtttggcagag540 attggtcgtgacggcgtcctggctctcctcagtgattcggccaatgcagacagcaatatt600 caggtggctagtgaaagtgaagttagggatgaaattacccaaactattgctgactgggaa660 ggtcgtatcatcgttgcagctgtttccagtaatctttctcgtattcagcagatttttgac720 gctgcggataaaacaggtcgacgtatcgtcttgacaggatttgatattgaaaatatcgtc780 SO cgcacagcgattcgtcttaagaagttgtctttagccaacgaaattctcttgattaagcct840 aaagatatgtctcgctttgaagaccatgagttgattattcttgagacaggtcgtatgggt900 gaacctatcaatggacttcgtaagatgtcgattggtcgccatcgttatgtagaaatcaag960 gatggggacctggtctatattgctacggctccgtctattgctaaagaagcctttgttgcg1020 cgtgtagaaaatatgatttatcaggcaggtggggttgtcaaattgattacccaaagttta1080 catgtatcagggcacggaaatgtgcgtgatttgcagctgatgatcaatcttttgcaacct1140 aagtacctcttccctgtccaaggggagtatcgtgagttggatgctcacgctaaggctgcc1200 atggcagttgggatgttgccagaacgcatcttcattcctaaaaaggggacgaccatggct1260 tacgagaatggagactttgttccagctggatcggtttcagcaggagatatcttaattgat1320 gggaatgccattggtgatgttggaaatgttgttcttcgtgaccgtaaggtcttgtcagag1380 gatggaattttcatcgtggctattacagtcaaccgtcgtgagaagaaaattgtggctaga1440 gctcgtgttcacacgcgtggatttgtttatctcaagaagagtcgcgatattctccgtgaa1500 agttcagaattgattaaccaaacggtagaagattatcttcaaggagatgactttgactgg1560 gcagatcttaaagggaaggttcgagataatttgaccaagtatctctttgaccaaaccaag1620 cgtcgtccagctattttaccagtagtcatggaagcaaaatas ~ 162 <210> 18 <211> 951 <212> DNA

<213> Streptococcus pneumoniae <400> 18 1$ atgacaaaagaatttcatcatgtaacggtcttactccacgaaacgattgatatgcttgac60 gtaaaacctgacggtatctacgttgatgcgactttgggtggagcaggccatagcgagtat120 ttattaagtaaattaagtgaaaaaggccatctctatgcctttgaccaggatcagaatgcc180 attgacaatgcgcaaaaacgcttggcaccttacattgagaagggagtggtgacctttatc240 aaggataacttccgtcatttacaggcacgtttgcgcgaagctggtgttcaggaaattgat300 ~ ggaatttgttatgacttgggagtgtctagtcctcaattggaccagcgtgagcgtggtttt360 tcttataaaaaggatgcgccactggacatgcggatgaatcaggatgctagtctgacagcc420 tatgaagtggttaatcattatgactatcatgatttggttcgtattttcttcaaatacggt480 gaggataaattctctaaacagattgcgcgtaagattgagcaagcgcgtgaagtgaagccg540 attgagacaacgactgagttagcagagattatcaagttggtcaaacctgccaaggaactc600 S aagaagaagggtcatcctgctaagcagattttccaggctattcgaattgaagtcaatgat660 gaactgggggcggcagatgagtccatccagcaggctatggatatgttggctctggatggt720 agaatttcagtgattacctttcattccttagaagaccgcttgaccaagcaattgttcaag780 gaagcttcaacagttgaagttccaaaaggcttgcctttcatcccagatgatctcaagccc840 aagatggaattggtgtcccgtaagccaatcttgccaagtgcggaagagttagaagccaat.900 ~ aaccgctcgcactcagccaagttgcgcgtggtcagaaaaattcacaagtaa 951 <210> 19 .

<211> 999 <212> DNA

35 <213> Streptococcus eumoniae pm <400> 19 atgagtagaattttagataatgagataatgggggatgaggagttagtagaacgcacgctc60 cgtcctcagtatttacgtgaatatatcggacaggataaggtcaaggaccagctacaaatc120 ~ tttattgaagctgccaaaatgcgggatgaagcgctggatcatgtgctcttatttgggcct180 ccaggtctcgggaaaacgaccatggcctttgttattgccaacgaactgggagtcaatctt240 aagcagacgtcgggtccagtcattgaaaaagccggagatctggtagctattttgaatgag300 ttagagcctggggatgtactttttattgatgagatccatcgtttgccaatgtcagtggaa360 gaggtgctttatagtgctatggaggacttctacatcgatattatgattggggctggtgag420 4S ggtagtcgtagtgttcatttggagttaccaccttttaccttgattggtgcgacgactcgg480 gctggtatgctctccaatccgctacgggcacgttttgggattacaggccatatggagtat540 tatgcccatgctgacttgacagaaattgtcgagcggacggcagatatttttgagatggaa600 atcactcatgaggcagcatctgagttggccctacgtagtcgtgggacccctcgtattgcc660 aatcgtctcctcaagcgcgtgcgcgattttgcccagataatggggaatggggtaattgat720 50 gatattattaccgataaggctttgactatgctggatgttgaccatgaaggtttggactat780 gtggatcaaaaaatccttcgtaccatgattgagatgtacagtggaggacctgttggtcta840 ggaactctttctgtgaatatcgccgaagagcgtgagacagttgaagacatgtatgagcct900 tacttgattcaaaaaggttttatcatgcggacacggtctggacgggtggcgactgctaag960 gcatatgagcacttaggttatgaatacagtgaaaaataa 999 <210> 20 <211> 1311 <212> DNA
<213> Streptococcus pneumoniae <400> 20 $ atgagtatgtttttagatacagctaagattaaggtcaaggctggtaatggtggcgatggt60 atggttgcctttcgtcgtgaaaaatatgtccctaatggaggcccttggggtggtgatggt120 ggtcgtggaggcaatgtggtcttcgttgtagacgaaggactacgtaccttgatggatttc180 cgctacaatcgccatttcaaggctgattctggtgaaaaagggatgaccaaagggatgcat240 ggtcgtggtgctgaggaccttagagttcgagtatcacaaggtacgactgttcgtgatgcg300 gagactggcaaggttttaacagatttgattaaacatgggcaagaatttatcgttgcccac360 ggtggtcgtggtggacgtggaaatattcgttttgcgacaccaaaaaatcctgcaccggaa420 atctctgaaaatggagaaccaggtcaggaacgtgagttacaattggaactaaaaatcttg480 gcagatgtcggtttagtaggattcccatctgtagggaagtcaacacttttaagtgttatt540 acctcagctaagcctaaaattggtgcctaccactttaccactattgtaccaaatttaggt600 atggttcgcacccaatcaggtgaatcctttgcagtagccgacttgccaggtttgattgaa660 ggggctagtcaaggtgttggtttgggaactcagttcctccgtcacatcgagcgtacacgt720 gttatccttcacatcattgatatgtcagctagcgaaggccgtgatccatatgaggattac780 ctagctatcaataaagagctggagtcttacaatcttcgcctcatggagcgtccacagatt840 attgtagctaataagatggacatgcctgagagtcaggaaaatcttgaagaatttaagaaa900 0 aaattggctgaaaattatgatgaatttgaagagttaccagctatcttcccaatttctgga960 ttgaccaagcaaggtctggcaacacttttagatgctacagctgaattgttagacaagaca1020 ccagaatttttgctctacgacgagtccgatatggaagaagaagcttactatggatttgac1080 gaagaagaaaaagcctttgaaattagtcgtgatgacgatgcgacatgggtactttctggt1140 gaaaaactcatgaaactctttaatatgaccaactttgatcgtgatgaatctgtcatgaaa1200 ~S tttgcccgtcagcttcgtggtatgggggttgatgaagcccttcgtgcgcgtggagctaaa1260 gatggggatttggtccgcattggtaaatttgagtttgaatttgtagactag 1311 <210> 21 <211> 519 30 <212> DNA

<213> Streptococcus eumoniae pn <400> 21 atgaactactttaatgttgggaaaatcgttaatacgcagggattacagggtgagatgcga60 S gtcttgtctgtgacggattttgcagaagaacggtttaaaaaaggagctgagctggctttg120 tttgatgaaaaagatcagtttgtccaaacagtgaccatcgctagccaccgtaaacagaag180 aactttgacattattaaattcaaagatatgtaccatatcaatactatcgaaaagtacaag240 ggatacagtctcaaggtcgctgaggaagatttgaatgacctagacgatggtgaattttac300 tatcacgagattatcggtttggaagtctatgagggtgatagcttggttggaaccatcaag360 40 gaaatcctgcaaccaggtgctaatgatgtctgggtggtcaaacgaaaaggcaaacgtgat420 ttgcttttaccttatatcccaccagtggttctcaatgttgatattccaaataaacgggtc480 gatgtggaaatcttagaagggttagacgatgaagattga ~ 519 <210> 22 45 <211> 720 <212> DNA

<213> Streptococcus pneumoniae <400> 22 50 atgaagattg atattttaac cctctttcca gagatgtttt ctccactgga gcactcaatc 60 gttggaaagg ctcgagaaaa agggctcttg gatatccagt atcataattt tcgagaaaat 120 gctgaaaagg cccgtcat,gt agatgatgag ccctacggag gcggtcaggg catgttgctc 180 agagcacaac ctattttcga ttcctttgat gctattgaaa agaaaaatcc gcgcgttatt 240 ctcctcgatc ctgctggaaa gcagtttgat caggcttatg ctgaagattt ggctcaagag 300.
SS gaagagctaa tctttatctg tgggcactat gagggttatg atgagcgcat taagaccttg 360 gtaacagatg agatttccct aggcgactat gtcctcactg gtggagaatt ggcagctatg 420 accatgattg atgctacagt tcgcctgatt ccagaagtga ttggcaagga gtctagccac 480 caagatgata gtttttcttc aggtctttta gaatat~catc agtacacacg tccctatgat 540 tatcgaggca tggtcgtgcc agatgtattg atgagtggcc atcatgaaaa gattcgtcag 600 tggcgattgt acgagagttt aaagaaaacc tacgagcgca gaccggattt acttgaacat 660 tatcaactga cagtagaaga agaaaaaatg ctggcagaaa tcaaagaaaa caaagaataa 720 <210> 23 <211> 561 <212> DNA
<213> Streptococcus pneumoniae <400> 23 atgattgaag caagtaaa~tt aaaagctggt atgacctttg aaacagctga cggcaaattg 60 attcgcgttt tggaagctag tcaccacaaa ccaggtaaag gaaacacgat catgcgtatg 120 aaattgcgtg atgtccgtac tggttctaca tttgacacaa gctaccgtcc agaggaaaaa 180 IS tttgaacaag ctattatcga gactgtccca gctcaatact tgtacaaaat ggatgacaca 240 gcatacttca tgaatacaga aacttacgac cagtacgaaa tccctgtagt caatgttgaa 300 aacgaattgc tttacatcct tgaaaactct gatgtgaaaa tccaattcta cggaactgaa 360 gtgatcggtg tcaccgttcc tactactgtt gagttgacag ttgctgaaac tcaaccatct 420 atcaaaggtg ctactgttac aggttctggt aaaccagcaa cgatggaaac tggacttgtc 480 2~ gtaaacgttc cagacttcat cgaagcagga caaaaactcg ttatcaacac tgcagaagga 540 acttacgttt ctcgtgccta a 561 <210> 24 <211> 1572 25 <212> DNA
<213> Streptococcus pneumoniae <400> 24 atggcatttgaaagtttaacagaacgtttgcagaacgtctttaaaaatctacgtaaaaaa60 ~ ggaaaaatctctgaatctgatgtccaagaggcaaccaaagaaattcgcttggccttgctc120 gaggccgacgttgccttgcctgttgtaaaggactttatcaagaaagttcgtgagcgtgca180 gtcgggcatgaggtcattgatacacttaatcctgcgcaacagattattaaaatcgttgat240 gaggaactgacagccgttttaggttctgatacggcagaaattatcaagtcacctaagatt300 ccaaccatcatcatgatggttggtttacaag.gggctggtaaaacaacctttgctggtaaa360 3S ttggccaacaaactcaagaaagaagaaaatgctcgtcctttgatgattgcggcggatatt420 tatcgtccagctgccattgaccagcttaagaccttgggacaacagattgatgtgcctgtc480 tttgcacttggaacagaagtaccagctgttgagattgtacgtcaaggtttggagcaagcc540 caaactaatcataacgactatgtcttgattgatactgcgggtcgtttgcagattgatgag600 ctcctcatgaatgagcttcgtgatgtgaaa,acattggctcaaccaaatgaaatcttgctt660 ~ gtcgttgatgctatgattggtcaggaagcagccaatgttgcgcgtgagtttaatgctcag720 ttggaagtgactggggtcatccttaccaagattgatggcgatactcgtggtggtgctgct780 ctgtctgttcgtcacattactggaaaaccaatcaagttcactggtacaggtgaaaagatt840 acggacattgaaaccttccacccagaccgcatgtctagccgtatccttggtatgggggat900 atgctcactttgattgagaaagcttctcaggaatacgatgaacaaaaagcccttgaaatg960 4S gctgagaagatgcgcgaaaacacctttgattttaatgatttcatcgatcaattagatcag1020 gtgcaaaatatggggccgatggaagacttgctcaagatgattccaggtatggcaaacaat1080 ccagcccttcaaaacatgaaggtggatgaacgccagattgctcgtaaacgtgccattgtg1140 tcttcgatgacacctgaagagcgtgaaaacccagatttgttaaatccaagccgtcgccgt1200 cgtattgctgctggttctggaaatacattcgtcgaagtcaataaattcatcaaggacttt1260 S~ aaccaggctaaacagctcatgcagggtgttatgtctggggatatgaataaaatgatgaag1320 caaatggggattaatccaaataaccttcctaaaaatatgccaaatatgggaggaatggat1380 atgtctgcccttgaaggaat, ggcggtatgcctgacttatcagctctcgga1440 gatgggacaa ggagcaggaatgccagatatgagccagatgtttggtggcggtttgaaaggtaaaattggt1500 gaatttgctatgaaacagtccatgaaacgtatggctaacaaaatgaagaaagcgaagaag1560 55 aaacgcaagtas 1572 <210> 25 <211> 846 <212> DNA
<213> Streptococcus pneumoniae S <400> 25 atgtatcttattgaaattttaaaatctatcttcttcgggattgttgaaggaattacggaa60 tggttgccgatttccagtacaggtcatttgattttagcagaggagtttatccaataccaa120 aatcaaaatgaagcctttatgtccatgtttaatgtcgtgattcagcttggtgctatttta180 gcagttatggtgatttattttaacaagctcaatccttttaaaccgactaaggacaaacag240 1~ gaagttcgtaagacttggagactatggttgaaggtcttgattgctactttacctttactt300 ggtgtctttaaatttgatgattggtttgatacccacttccataacatggtttcagttgct360 ctcatgttgattatctacggggttgccttcatctatttggaaaagcgcaataaagcgcgt420 gctatcgagccaagtgtaacagagttggacaagcttccttatacgaccgctttctatatc480 ggactcttccaagttcttgctcttttaccagggactagccgttcaggtgcaacgattgtc540 IS ggtggtttgttaaatggaaccagtcgttcagttgtgacagaatttaccttctatcttggg600 attcccgttatgtttggagctagtgccttaaagattttcaaatttgtgaaagccggagaa660 ctcttgagctttgggcaattgtttttgctcttggtcgcgatgggagtagcttttgcggtc720 agcatggtggctattcgcttcttgaccagctatgtgaaaaaacacgacttcacccttttt780 ggtaaataccgtatcgtgcttggtagtgttttgctactttacagttttgtccgtttattt840 2~ gtataa 846 <210> 26 <211> 1290 <212> DNA

ZS <213> Streptococcus pneumoniae <400> 26 atgggattatttgaccgtctattcggaaaaaaagaagaacctaaaatcgaagaagttgta60 ~

aaagaagctctggaaaatcttgatttgtct~gaagatattgagcctgccttcacagaagct120 3~ gaggaagtttctcaagaagaagcagaggttgaaagttctgaagaatctgtgttccaagaa180 gaggatagtcaagacacagtcgaagaaaatctggatttagagccagttgtagaggtttct240 caagaagaagtagaagaatttccaaactcacaagaagtcacagaggaagagaagcttgag300 cacgaaggaactgtagaagaaaataattttgaagtgcttgaaccagaagctcctcaaaca360 gaagaaactgttcaggaaaaatatgaccgcagtcttaagaaaactcgcacaggtttcggt420 35 gcccgcttgaatgccttctttgctaacttccgctctgttgacgaagaatttttcgaggaa480 ctggaagaactgttgattatgagtgatgttggtgtccaagtcgcttctaacttaacggag540 gaactacgt t acgaagccaagcttgaaaatgccaagaaacctgatgcacttcgtcgtgtc600 atcattgagaaattggttgagctttatgaaaaggatggtagctacgatgaaagcatccac660 ttccaagataacttgacagttatgctctttgttggtgtgaatggtgttgggaaaacaact720 4~ tctatcggaaaactagcccaccgctacaaacgagctggtaagaaggtcatgctggttgca780 gcagataccttccgtgcgggtgcagtagctcagctagctg,aatggggccgacgagtagat840 gttccagtagtaactggacctgaaaaagctgatccagccagcgtggtctttgatggtatg900 gaacgtgccgtggctgaaggtatcgatattctcatgattgatactgctggtcgtctgcaa960 aataaggataaccttatggctgagttggaaaagattggtcgtattatcaaacgtgttgtg1020 45 ccagaagcaccacatgaaac.cttcttggcacttgatgcatcaacaggtcaaaatgcccta1080 gtacaggccaaagaattttcgaaaatcacacctttaacgggaattgttttgactaagatt1140 gatggaactgctcgaggaggtgtggttctagccattcgtgaagaactcaatattcctgta1200 aaattgattggttttggtgaaaaaatcgatgatattggagagtttaactcagaaaacttc1260 atgaaaggtctcttggaaggtttaatctaa 1290 5~

<210> 27 <211> 498 <212> DNA
<213> Streptococcus pneumoniae <400> 27 atgtatattg aaatggtaga tgaaactggt caagtttcaa aagaaatgtt gcaacaaacc 60 caagaaattttggaatttgcagccaaaaaattaggaaaagaagacaaggagatggcagtc120 acttttgtgaccaatgagcgtagtcatgaacttaatctggagtaccgtgacaccgaccgt180 ccgacagatgtcatcagccttgagtataaaccagaattggaaattgcctttgacgaagag240 gatttgcttgaaaatccagaattggcagagatgatgtctgagtttgatgcctatattggg300 gaattgttcatctctatcgataaggctcatgagcaggccgaagaatatggtcacagcttt360 gagcgtgagatgggcttcttggcagtacacggctttttacatattaacggctatgatcac420 tatactccggaagaagaagcggagatgttcggtttacaagaagaaattttgacagcctat480 ggactcacaagacaataa 498 <210> 28 <211> 768 <212> DNA

<213> Streptococcus pneumoniae <400> 28 atgagtattcgagtaattattgccggttttaagggaaagatgggccaggctgcttgtcag60 atggtattgactgatccagacttggacttggtggcagttttggatccttttgagtctgag120 tcagaatggcagggtattcctgttttcaaggataaggctgatttagctggttttgaagcg180 gatgtctgggtagattttactactccagctgttgcctacgaaaatacacgttttgctctt240 gaaaatggctttgctccagtagttggaacgactggtttcacgagtgaagaaattgcagag300 ctaaaagaattttctcgtgcccaagacttgggtggcctgattgeccctaactttgccttg360 ggtgctgtcttactcatgcaatttgcgacgcaggctgccaaatatttcccaaatgtggag420 attattgagctccatcatgacaagaaaaaggatgctccgagtggaacagccattaaaaca480 gctgagttgatggcagaggttcgagagtcaattcagcaaggtgcagcagatgaggaagag540 ~S ctgattgctggtgctcgtggtgctgacttt~gatggtatgcgcatccactcagttcgtttg600 ccaggcttggtagctcatcaggaagtcatctttggcaatcagggagaagggttgaccctc660 cgtcatgactcctatgatcgcatctccttcatgacaggagtcaatttgggaattaaagaa720 gttgtcaagcgtcatgagcttgtctatggattagaacacttattatga 768 <210> 29 <211> 276 <212> DNA

<213> Streptococcus pneumoniae <400> 29 atggcaaacaaacaagatttgatcgctaaagtagcagaagctacagaattaactaagaaa60 gactcagcagcagcagttgaagctgtatttgcagcagtagctgactatcttgcagctggt120 gaaaaagttcagttgatcggttttagtaactttgaagttcgt.gagcgcgcagaacgtaaa180 ggtcgcaacccacaaactggtaaagaaatgacaattgcagcttctaaagtaccagcattc240 aaagctggtaaagctcttaaagacgctgttaaataa 276 <210> 30 <211> 921 <212> DNA

<213> Streptococcus pneumoniae <400> 30 atgactaaaacagcctttttatttgctggtcaaggtgcccagtatctagggatgggacgg60 gatttctatgatcagtatccgattgttaaagaaacgattgatcgagcgagtcaggtgctc120 SO ggttatgatttgcgttatctcatcgatacggaagaggacaaactcaatcagacccgctat180 acgcaaccagccattctagcgacttcggttgctatctaccgtttattgcaagaaaagggc240 tatcagcctgatatggtcgctggtttgtctcttggagaatactctgccttggtggcaagc300 ggcgccttggattttgaagatgcggttgccttggtagctaagcgtggagcctatatggaa360 gaagcggctc,ctgctgactctggcaagatggtagcagttctcaatacgccagtagaggtc420 SS attgaagaagcctgtcaaaaagcttctgaacttggagtggttactccagccaactataac480 acacctgcacaaatcgtcattgctggagaagtggttgcagttgatcgagcggttgaactt540 ttgcaagaagcaggtgccaaacgcttgattcctcttaaggtgtcaggtccctttcacacc600 gctctccttgagccagctagccagaaactagctgaaactctagctcaggtaagtttttca660 gattttacttgtcccctagtcggcaatacagaagctgctgtgatgcaaaaagaggacatt720 gctcagctcttgacgcgtcaggtcaaggaacccgttcgtttctatgaaagtattggggtc780 atgcaagaagcaggcataagcaactttatcgagattggaccggggaaagtcttgtcaggt840 tttgttaaaaaaattgatcaaactgctcacttagctcatgtggaagatcaagcgagttta900 gtagcacttttagaaaaatag 921 <210> 31 <211> 732 1~ <212> DNA

<213> Streptococcus pneumoniae <400> 31 atgaaactagaacataaaaatatctttattacaggttcgagtcgtggaattggtcttgcc60 atcgcccacaagtttgctcaagcaggagccaacattgtcttaaacagtcgtggggcaatc120 tcagaagaattgctcgctgagttttcaaactatggtatcaaggtggttcccatttcagga180 gatgtatcagattttgcagacgctaagcgtatgattgatcaagctattgcagaactgggt240 tcagtagatgttttggtcaacaatgcagggattacccaagatactcttatgctcaagatg300.

acagaagcagattttgaaaaagtgctcaaggtcaatctgactggtgcctttaatatgaca360 caatcagtcttgaaaccgatgatgaaagccagagaaggtgctatcattaatatgtctagt420 gttgttggtttgatggggaatattggtcaagctaactatgctgcttctaaggctggcttg480 attggctttaccaagtctgtggcacgcgaggtcgctagtcggaatatacgagtcaatgtg540.

attgctccaggaatgattgagtctgatatgaccgctatcttatcagataagattaaggaa600 ~gctacactagctcagattccgatgaaagaatttgggcaggcagagcaggttgcagatttg660 S acagtatttttagcaggccaagattatctaactggtcaag~tggttgccattgatggtggc720 ttaagtatgtag 732 <210> 32 <211> 831 ~ <212> DNA

<213> Streptococcus pneumoniae <400> 32 atgggagtgaaaaagaaactaaagttgactagtttgctaggactgtctctgttaatcatg60 35 acagcctgtgcgactaatggggtaactagcgatattacagccgaatcggctgatttttgg120 agtaaattggtttacttctttgcggaaatcattcgctttttatcgtttgatattagtatc180 ggagtggggattattctctttacggtcttg,attcgtacagtcctcttgccagtctttcag240 gtgcaaatggtggcttctaggaaaatgcaggaagctcagccacgcattaaggcgcttcga300 gaacaatatccaggtcgagatatggaaagcagaaccaaactagagcaggaaatgcgtaaa360 ~ gtatttaaagaaatgggtgtcagacagtcagactctctttggccgattttgattcagatg420 ccggttattttggccctgttccaagccctatcaagagttgactttttaaagacaggtcat480 ttcttatggattaaccttgg=i:~agtgtggatacaacccttgttcttccgattttagcagca540 gtattcacctttttaagtacttggttgtccaacaaagctttgtctgagcgaaatggcgct600 acgactgcgatgatgtatgggattccagtcttgatttttatctttgcagtttatgcgcca660 45 ggtggagtcgccctatactggacagtgtctaatgcttatcaagtcttgcaaacctatttc720 ttgaataatccattcaagattatcgcagagcgcgaggccgtagtacaggcacaaaaagat780 ttggaaaatagaaaaagaaaagccaagaaaaaggctcagaaaacgaaataa 831 <210> 33 . 5~ <211> 1230 <212> DNA
<213> Streptococcus pneumoniae <400> 33 SS atgaagatta gtaagaggca cttattaaat tattccatct tgattcccta cttactttta 60 tctattttgg gcttgattgt ggtctattcg accaccagtg ctattttaat tgaagaaggc 120 aagagcgcct tgcagttggt tcgaaaccaa ggaatctttt ggattgttag tttgatactg 180 attgccttaatttataaattgagactagattttttgagaaatgagcgactaatcatttta240 gttatattaatagaaatgcttttattgttcttggctcgttttattggtatttcagtaaac300 ggggcatacggttggatttcggttgcaggagtaactattcagccagctgagtacttaaaa360 atcattattatttggtatttagctcaccgattctccaaacagcaagaagaaatagctact420 tatgattttcaagttttgactcaaaatcaatggcttccccgtgcttttaatgattggcga480 ttcgttctcctagttctgattggaagtttgggaattttccctgatttaggaaatgcgact540 attttagtcttggtttccttgattatgtatacagttagtggaatcgcttatcgctggttt600 tcaaccattctggcgctcgtatctgccacttctgtctttgtcttgaccactatcagccta660 atcggtgttgagaccttttcaaaaattccagtatttggctatgtagccaagcgctttagt720 gccttttttaatccttttgccgatcgtgctgatgcaggtcaccagttagctaattcttat780 tttgccatggtcaatggtggttggtttggtctaggtcttggaaactcgattgaaaaacga840 ggttatttgccagaagctcatacagactttgtcttttctatcgtgattgaagaatttggc900 tttgttggtgccagtcttattttagctctcttgtttttcatgattttgcggattatcttg960 gtcggtatccgagcggagaatcctttcaatgccatggttgcactcggtgtcggagggatg1020 IS atgttggttcaggtatttgtcaatatcggagggatttcgggcttgattccatctacagga1080.

gtgactttccctttcttatcccagggtggaaatagtcttctagtcttatcagtggcagta1140 gcctttgtcttaaatattgatgccagtgaaaaacgcgctaagttgtaccgagaattggaa1200 aatcaaccaatgaaccttctgttgaagtag 1230 ~ <210> 34 .

<211> 1260 <212> DNA

<213> Streptococcus pneumoniae ZS <400> 34 atgctcggaattttaacctttattctggtttttgggattattgtagtggtgcacgagttc60 gggcacttctactttgccaagaaatcagggattttagtacgtgaatttgccatcggtatg120 ggacctaaaatctttgctcacattggcaaggatggaacggcctataccattcgaatcttg180 cctctgggtggctatgtccgcatggccggttggggtgatgatacaactgaaatcaagaca240 30 ggaacgcctgttagtttgacacttgctgatgatggtaaggttaaacgcatcaatctctca300 ggtaaaaaattggatcaaacagccctccctatgcaggtgacccagtttgattttgaagac360 aagctctttatcaaaggattggttctggaagaagaaaaaacatttgcagtggatcacgat420 gcaacggttgtggaagcagatggtactgaggttcggattgcacctttagatgttcaatat480 caaaatgcgactatctggggcaaactgattaccaattttgcaggtcctatgaacaatttt540 35 atcttaggtgtcgttgttttttgggttttaatctttatgcagggtggtgtcagagat~gtt600 gataccaatcagttccatatcatgccccaaggtgccttggccaaggtaggagtaccagaa660 acggcacaaattaccaagatcggctcacatgaggttagcaactgggaaagcttgatccaa720 gctgtggaaacagaaaccaaagataagacggcaccgactttggatgtgactatttctgaa780 aaggggagtgacaaacaagtcactgttacacccgaagatagtcaaggtcgttaccttcta840 4~ ggtgttcaaccgggggttaagtcagattttctatccatgtttgtaggtggttttacaact900 gctgctgactcagctctccgaattctctcagctctgaaaaatctgattttccaaccggat960 ttgaacaagttgggtggacctgttgctatctttaaggcaagtagtgatgctgctaaaaat1020 ggaattgagaatatcttgtacttcttggcaatgatttccatcaatattgggatttttaat1080 cttattccgattccagccttggatggtggtaagattgtgctcaatatcctagaagccatc1140 45 cgccgcaaaccattgaaacaagaaattgaaacctatgtcaccttggccggagtggtcatc1200 atggttgtcttgatgattgctgtgacttggaatgacattatgcgactcttttttagataa1260 <210> 35 <211> 594 $0 <212> DNA

<213> Streptococcus pneumoniae <400> 35 atgtacgcatatttaaaaggaatcattaccaaaattactgccaaatacattgttcttgaa60 SS accaatggtattggttatatcctgcatgtggccaatccttatgcctattcaggtcaggtt120 aatcaggaggctcagatttatgtgcatcaggttgtgcgtgaggacgcccatttgctttat180 ggatttcgctcagaggatgagaaaaagctctttcttagtctaatttcggtctctgggatt240 ggtcctgtat,,,cagctcttgc tattatcgctgctgatgacaatgctggcttggttcaagcc300 attgaaaccaagaacatcacctacttgaccaagttccctaaaattggcaagaaaacagcc360 cagcagatggtgctggacttggaaggcaaggtagtagttgcaggagatgaccttcctgcc420 aaggtcgcagtgcaagcaagtgctgaaaaccaagaattggaagaagctatggaagccatg480 ttggctctgggctacaaggcaacagagctcaagaaaatcaagaaattctttgaaggaacg540 acagatacagctgagaactatatcaagtcggcccttaaaatgttggtcaaatag 594 <210> 36 <211> 774 l~ <212> DNA

<213> Streptococcus pneumoniae <400> 36 atgaagaataatcgtattttagcactttctggaaatgatatttttagtggtggtggactg60 IS tcagctgatttggctacctataccttgaacggcttgcatgggtttgtagcagtgacttgt120 ttgacagccttgacagaaaaaggatttgaagtctttccaactgatgataccatttttcaa180 catgaattagatagcttgcgtgatgtggaatttgggggaattaagattggtcttctccct240 actgtcagtgtggctgagaaggccttggactttatcaaacaacgcccaggagtacctgtg300 gtgttggatcctgtcttggtctgcaaggaaacgcatgatgtagctgtcagtgagctctgc360 2~ caagagttgattcgcttcttcccttatgtcagtgtgattacgcctaatctcccagaagca420 gaattattatccggtcaggaaattaaaaccttggaagacatgaaaactgcagcgcagaaa480 ttgcatgatttaggag~cgccagcagtcattatcaagggaggcaatcgtcttagtcaggac540 aaggctgtggatgtcttttatgatggacagacctttactatcctagaaaatccagttatc600 caaggccaaaatgctggtgcaggttgtacctttgcctctagcattgccagtcacctggtt660 $ aaaggtgataaatttttgccagcagtagaaagctctaaggctttcgtttatcgtgctatt720 gcacaagcagatcagtatggagtaagacaatatgaagcaaacaaaaacaactaa 774 <210> 37 <211> 1239 30 <212> DNA

<213> Streptococcus pneumoniae <400> 37 atgattgaaacggagaaaaaagaggagcgagtcctgctgattggtgtggaattgcagggt60 3S atggacagttttgacctctccatggaagaattggctagtttagcgaaaacggcaggggca120 gtcgttgtagatagctacagacaaaaacgtgaaaaatatgattccaagaccttcgtcggc180 tctggtaagttggaagagattgcgcttatggtggatgcagaagaaatcactactgtcatc240 gtcaacaatcgtctgaccccaaggcagaatgtcaatctagaggaagttctcggtgttaag300 gtcattgaccgtatgcagttgattttggatatctttgccatgcgggctcgaagccatgaa360.

~ gggaagctccaagtccacctagcccaattcaaatacctcttgcctcgcttggttggtcag420 gggattatgctcagccgtcaggcagggggaattggttcccgtggtcctggtgaaagccaa480 ctggagctgaaccgtcgtagcgttcgcaatcaaatcacggatatcgagcgccagcttaag540 gtggttgagaaaaatcgtgcgactgtcagagaaaaacgtttggagtctagcacttttaag600 attggtttgattggttatactaatgctgggaaatcaactatcatgaacatcttgaccagt660 4S aagacccagtatgaagcagatgagctctttgcgactctggatgcgacaaccaagagtatt720 catctgggaggcaatctccaagtaactttgacagataccgttggctttatccaagatttg780 ccgacagagttggtgtccagtttcaagtcaaccttggaagaaagcaagcatgtggacctt840 ctggttcatgttatcgatgctagcaatccttaccacgagg~agcatgaaaaaacggttctc900 tccatcatgaaagacctggacatggaagatattcctcacttgacgctttataataaagcg960 5~ gatttggtggaggatttcacgcctacccaaacgccatataccctcatttctgccaagtct1020 gaggacagtcgtgaaaacttgcaagcattattgctagataagattaaggaaatttttgaa1080 gcatttaccctgcgagtgcctttttcaaagtcctacaagattcatgatttagagagtgtt1140 gcaattctggaagaacgtgattatcaggaagacggcgaagtgattacagg.ctacatttcc1200 gagaaaaataaatggaggttagaagaattttatgactga 1239 <210> 38 <211> 483 <212> DNA
<213> Streptococcus pneumoniae <400> 38 atggcagaaaaaacatatcctatgacccttgaggaaaaggaaaaacttgaaaaagaatta60 gaagaattgaaattggttcgtcgaccagaagtggtagaacgcattaagattgcccgttca120 tacggtgacctttcagaaaacagtgagtacgaagcagcta~aggatgaacaagcctttgtc180 gaaggacaaatctctagcttagaaacaaaaatccgctatgctgaaatcgtcaatagcgac240 gcagttgcccaggacgaagtagcgattggtaaaacagtcaccatccaagaaattggtgag300 gacgaagaagaagtttatattatcgtaggttcagctggtgcggatgcctttgcaggtaag360 gtttcaaatgaaagcccaattgggcaggccttgattggcaagaaaacaggtgatacagca420 accattgaaacgcctgttggtagctatgatgtaaaaatcttgaaggttgaaaaaacagcc480 taa 483 IS <210> 39 <211> 570 <212> DNA

<213>.Streptococcus pneumoniae <400> 39 atgaccaaattacttgtaggcttgggaaatccaggggataaatattttgaaacaaaacac60 aatgttggttttatgttgattgatcaactagcgaagaaacagaatgtcacttttacacac120 gataagatatttcaagctgacctagcatcctttttcctaaatggagaaaaaatttatctg180 gttaaaccaacgacctttat~gaatgaaagtggaaaagcagttcatgctttattaacttac240 2S tatggtttggatattgacgatttacttatcatttacgatgatcttgacatggaagttggg300 aaaattcgtttaagagcaaaaggctcagcaggtggtcataatggtatcaagtctattatt360 caacatataggaactcaggtctttaaccgtgttaagattggaattggaagacctaaaaat420 ggtatgtcagttgttcatcatgttttgagtaagtttgacagggatgagtatatcggtatt480 ttacagtctgttgacaaagttgacgattctgtaaactactatttacaagagaaaaatttt540-~ gagaaaacaatgcagaggtataacggataa 570 <210> 40 <211> 852 <212> DNA

35 <213> Streptococcus pneumoniae <400> 40 atgattttaattacaggggcaaatggccaattaggaacggaacttcgctatttattggat60 gaacgtaatgaagaatacgtggcagtagatgtggctaagatggacattaccaatgaagaa120 ~ atggttgagaaagtttttgaagaggtgaaaccgactttagtctaccattgtgcagcctac180 accgctgttgatgcagcagaggatgaaggaaaagagttggacttcgccatcaatgtgacg240 gggacaaaaaatgtcgcaaaagcatctgaaaagcatggtgcaactctagtttatatttct300 acggactatgtctttgacggtaagaaaccagttggacaagagtgggaagttgatgaccga360 ccagatccacagacagaatatggacgcactaagcgtatgggggaagagttagttgagaag420 4S catgtgtctaatttctatattatccgtactgcctgggtatttggaaattatggcaaaaac480 ttcgtttttaccatgcaaaatcttgcgaaaactcataagactttaacagttgtaaatgat540 cagtacggtcgtccgacttggactcgtaccttggctgagttcatgacctacctagctgaa600 aatcgtaaggaatttggttattatcatttgtcaaatgatgcgacagaagacacaacatgg660 tatgattttgcagttgaaattttgaaagatacagatgtcgaagtcaagccagtagattcc720 50 agtcaatttccagccaaagctaaacgtccgctaaactcaacgatgagcctggccaaagcc780 aaagctactggatttgttattccaacttggcaagatgcattgcaagaattttacaaacaa840 gaagtgagatas 852 <210> 41 SS <211> 1224 <212> DNA

<213> Streptococcus pneumoniae <400> 41 atgaaacgttctctcgactcaagagtcgattacagtttgctcttgccagtattttttcta60 ctggtcatcggtgtggtggctatctatatagccgttagtcatgattaccccaataatatt120 ctgcccattttagggcagcaggtcgcctggattgccttggggcttgtgattggttttgtg180 gtcatgctctttaatacagaatttctttggaaggtgaccccctttctatatattttaggc240 ttgggacttatgatcttgccgattgtattttataatccaagcttagttgcatcaacgggt300 gccaaaaactgggtatcaata'aatggaattaccctattccaaccgtcagaatttatgaag360 atatcctatatcctcatgttggctcgtgtcattgtccaatttacaaagaaacataaggaa420 l~ tggagacgcacggttccgctggactttttgttaattttctggatgattctctttaccatt480 ccagtcctagttcttttagcacttcaaagtgacttggggacggctttggtttttgtagcc540 attttctcaggaatcgttttattatcaggggtttcttggaaaattattatcccagtattt600 gtgactgctgtaacaggagttgctggtttcttagctatctttattagcaaggacggacga660 gcttttcttcaccagattggaatgccgacctaccaaatcaatcggattttggcttggctc720 IS aatccctttgagtttgcccaaacaacgacttaccagcaggctcaagggcagattgccatt780 gggagtggtggcttatttggtcagggatttaatgcttcgaatctgcttatcccagttcga840 gagtcagatatgatttttacggttattgcagaagattttggctttattggctctgtcctg900 gttattgccctctatctcatgttgatttaccgtatgttgaagattactcttaaatcaaat960 aaccagttctacacttatatttccacaggtttgattatgatgttgctcttccacatcttt1020 2~ gagaatatcggtgctgtgactggactacttcctttgacggggattcccttgcctttcatt1080 tcgcaagggggatcagctattatcagtaatctgattggtgttggtttgcttttatcgatg1140 agttaccagactaatctagctgaagaaaagagcggaaaagttccattcaaacggaaaaag1200 gttgtattaaaacaaattaaataa 1224 25 <210> 42 <211> 609 <212> DNA

<213> Streptococcus pneumoniae 30 <400> 42 atgggaaaaat.catcggaatcactgggggaattgcctcaggtaagtcaactgtgacaaat60 tttctaaaacaccaagggctttcaagcagtggattgccgacgcagtgttccaccaactac120 agaaaacctggtggtcgtctgtttgaggctttagtacagcactttgggcaagaaatcatt180 cttgaaaacggagaactcaatcgccctctcatagctagtctcatcttttcaaatcctgaa240 35 gagcaaaaatggtctaatcaaattcaaggggagattatccgtgaggaactggctactttg300 agagaacagttggctcagacagaagagattttcttcatggatattcccctactttttgaa360 caggactacagcgattggtttgctgagacttggttggtctatgtggaccgagatgcccaa420 gtagaacgcttaatgaaaagggaccagttgtccaaagatgaagctgagtctcgtatggca480 gcccagtggccttta,gaaaaaaagaaagatttggccagccaggttcttgataataatggc540 ~ aatcagaaccagcttcttaatcaagtgcatatccttcttgaggga,ggtaggcaagatgac600 agagattaa 609 <210> 43 <211> 1260 45 <212> DNA

<213> Streptococcus pneumoniae <400> 43 atgagaaaaa ttgttatcaa tggtggatta ccactgcaag gtgaaattac tattagtggt 60 50 gctaaaaata gtgttgtggc cttaattcca gctattatat tggctgatga tgtggtgact 120 ttggattgtg ttccagatat ttcggatgta gccagtcttg tcgaaatcat ggaattgatg 180 ggagctactg ttaagcgtta tgacgatgtc ttggagattg atccaagagg tgttcaaaat 240 attccaatgc cttatggtaa aattaacagt cttcgtgcat cttactattt ttatgggagc 300 ctcttaggcc gttttggtga agcgacagtt ggtctaccgg gaggatgtga tcttggtcct 360 SS cgtccgattg acttacacct taaggcgttt gaagctatgg gtgccactgc tagctacgag 420 ggagataaca tgaagttatc tgctaaagat acaggacttc atggtgcaag tatttacatg 480 gatacggtta gtgtgggagc aacgattaat acgatgattg ctgcagttaa agcaaatggt 540 cgtactattattgaaaatgcagcccgtgaacctgagattattgatgtagctactctcttg600 aataatatgggtgcccatatccgtggggcaggaactaatatcatcattattgatggtgtt660 gaaagattacatgggacacgtcatcaggtgattccagaccgcattgaagctggaacatat720 atatctttagctgctgcagttggtaaaggaattcgtataaataatgttctttacgaacac780 ctggaagggtttattgctaagttggaagaaatgggagtgagaatgactgtatctgaagac840 agcatttttgtcgaggaacagtctaatttgaaagcaatcaatattaagacagctccttac900 ccaggctttgcaactgatttgcaacaaccgcttacccctcttttactaagagcgaatggt960 cgtggtacaattgtcgatacgatttacgaaaaacgtgtaaatcatgtttttgaactagca1020 aagatggatgcggatatttcgacaacaaatggtcatattttgtacacgggtggacgtgat1080 l~ ttacgtggggccagtgttaaagcgaccgacttaagagctggggctgcactagtcattgct1140 gggcttatggctgaaggtaaaactgaaattaccaatattgagtttatcttacgtggttat1200 tctgatattatcgaaaaattacgtaatttaggagcggatattagacttgttgaggattaa1260 <210> 44 <211> 696 <212> DNA

<213> Streptococcus -pneumoniae <400> 44 ~ atgtcaagaattgaattttcaccatctttgatgaccatggatttggacaaattcaaagag60 cagattacttttttgaatgataaagtagcatcttatcatatcgatattatggatggccat120 tttgttcccaatattaccttgtctccttggttcattcaagaagttcaaaaaattagtgac180 acacctttatcagttcatctgatggtcacagacccaaccttttgggtagatcaagttctc240 gatttacaatgtgagtatatttgtattcatgctgaagttctgaatggtcttgcttttcgt300 2S ttgattgataaaattcatgatgcaggtctaaaggctggtgttgtccttaatcctgaaaca360 cctgtttctacaatctttccctacattgatttacttgacaaagtaactattatgactgta420 gatccaggttttgcaggacaacgctttttggagtctaccttgtataaaatccaagaactc480 cgtcagcttagagttcagaatggttatcactacatcattgagatggatggttcttcgagt540 cgtaagactttcaaacaaattgatgtggcaggaccagatatttatgttataggtcgcagt600 30 ggattatttggtttggatgacgatattgccaaagcctgggatatctgttctagagattac660 gaagaaatgaccggaaaaacaatgccaatcaaataa 696 <210> 45 <211> 1125 _ 3S <212> DNA

<213> Streptococcus pneumoniae <400> 45 atgagaaatatggctttgacagcaggtatcgttggtttgccaaacgttggtaaatcaaca60 4~ ctatttaatgcaattacaaaagcaggagcagaggcagcaaactacccatttgcgactatt120 gatccaaatgttggaatggtggaagatccagatgaacgcctacaaaaactaactgaaatg180 ataactcctaaaaagacagttcccacaacatttgaatttacggatattgcagggattgta240 aaaggagcttcaaaaggagaagggctagggaataaattcttggccaatattcgtgaagta300 gatgcgattgttcacgtagttcgtgcttttgatgatgaaaatgtgatgcgcgagcaagga360 45 cgtgaagacgcctttgtagatccacttgcagatattgatacaattaatctggaattaatt420 cttgctgacttagaatcagtgaacaaacgatatgcgcgtgtagaaaagatggcacgtacg480 caaaaagataaagaatcagtagcagaattcaatgttcttcaaaagattaaaccagtccta540 gaagacgggaaatcagctcgtaccattgaatttacagatgaggaacaaaaggttgtcaaa600 ggtcttttccttttgacgactaaaccagttctttatgtagctaatgtggacgaggatgtg660 50 gtttcagaacctgactctatcgactatgtcaaacaaattcgtgaatttgcagcgacagaa720 aatgctgaagtagtcgttatttctgcgcgtgctgaggaagaaatttctgaattggatgat780 gaagataaaaaagagtttcttgaagccattggtttgacagaatcaggtgtagataagttg840 acgcgtgcagcttaccacttgcttggattgggaacttacttcacagctggtgaaa.aagaa900 gttcgcgcttggactttcaaacgtggtatgaaggctcctcaagcagctggtattatccac960 SS tcagactttgaaaaaggctttattcgtgcagtaaccatgtcatatgaagatctagtgaaa1020 tacggatctgaaaaggccgtaaaagaagctggacgcttgcgtgaagaaggaaaagaatat1080 atcgttcaagatggcgatatcatggaattccgctttaatgtctaa 1125 gtgactgctgtaacaggagttgctggtttcttagctatctttattagcaaggacggacga660 gcttttcttcaccagattggaatgccgacctaccaaatcaatcggattttggcttggctc720 IS aatccctttgagtttgccca <210> 46 <211> 333 <212> DNA

<213> Streptococcus pneumoniae <400> 46 atggaaatcgaaaaaaccaatcgtatgaatgcgctctttgaattttatgcggcgcttttg60 acagataagcaaatgaattatatagagctttactacgctgatgattacagtcttgctgag120 to atagctgaggagtttggtgttagtcgtcaggctgtctatgacaatatcaagcgaacagaa180 aagattctggaagattatgagatgaaattgcacatgtactcggactacattgtccgtagt240 cagatttttgaccaaatcttggagcgctatcccaaggatgattttctgcaggagcagata300 gaaattttaacaagcattgataatagagaataa 333 IS <210> 47 <2l1> 672 <212> DNA

<213> Streptococcus pneumoniae ~ <400> 47 atgaccttagaatgggaagaatttctagatccttacattcaagctgttggtgagttaaag60 attaaacttcgtggtattcgtaagcaatatcgtaagcaaaataagcattctccaattgag120 tttgtgaccggtcgagtcaagccaattgagagcatcaaagaaaaaatggctcgtcgtggc180 attacttatgcgaccttggaacacgatttgcaggatattgctggcttacgtgtgatggtt240 2S cagtttgtagatgacgtcaaggaagtagtggatattttgcacaagcgtcaggatatgcga300 atcatacaggagcgagattacattactcatagaaaagcatcaggctatcgttcctatcat360 gtggtagtagaatatacggttgataccatcaatggagctaagactattttggcagaaatt420 caaattcgtactttggccatgaatttctgggcaacgatagaacattctctcaactacaag480 taccaaggggatttcccagatgagattaagaagcgactggaaattacagctagaatcgcc540 ~ catcagttggatgaagaaatgggtgaaattcgtgatgatatccaagaagcccaggcactt600 tttgatcctttgagtagaaaattaaatgacggtgtaggaaacagtgacgatacagatgaa660 gaatacaggtas 672 <210> 48 35 <211> 588 <212> DNA

<213> Streptococcus pneumoniae <400> 48 ~ atggaacttaatacacacaatgctgaaatcttgctcagtgcagctaataagtcccactat60 ccgcaggatgaactgccagagattgccctagcagggcgttcaaatgttggtaaatccagc120 tttatcaacactatgttgaaccgtaagaatctcgctcgtacatcaggaaaacctggtaaa180 acccagctcctgaacttttttaacattgatgacaagatgcgctttgtggatgtgcctggt240 tatggctatgctcgtgtttctaaaaaggaacgtgaaaagtgggggtgcatgattgaggag300 4S tacttaacgactcgggaaaatctccgtgcggttgtcagtctagttgaccttcgtcatgac360 ccgtcagcagatgatgtgcagatgtacgaatttctcaagtattatgagattccagtcatc420 attgtggcgaccaaggcggacaagattcctcgtggtaaatggaacaagcatgaatcagca480 atcaaaaagaaattaaactttgacccaagtgacgatttcatcctcttttcatctgtcagc540 aaggcagggatggatgaggcttgggatgcaatcttagaaaaattgtga 588 <210> 49 <211> 294 <212> DNA
<213> Streptococcus pneumoniae <400> 49 atgaaaacaa gaaaaatccc tttgcgcaag tctgttgtgt ctaacgaagt gattgataag 60 cgtgatttgc tccgcattgt taagaacaag gaaggacaag tctttattga tcctacgggc 120 aaggccaatg gccgcggcgc ttatatcaaa ctagacaatg cagaagccct agaggcgaaa 180 aagaagaagg tctttaaccg cagctttagc atggaagtgg aagaaagctt ttatgacgag 240 ttgatcgctt atgtggatca caaagtgaaa agaagagagt tgggacttga ataa 294 <210> 50 <211> 312 <212> DNA
<213> Streptococcus pneumoniae <400> 50 atgttaaaaccctctattgataccttgctcgacaaggttccttcaaaatattcactcgta atcttggaagcaaaacgtgcccacgaattggaagcaggtgccccagcaactcaaggtttc aagtctgaaaaatcaactcttcgcgctttagaagaaatcgaatcaggaaacgttacaatt 1S cacccagatccagaaggaaaacgtgaagcagtgcgtcgccgtatcgaagaagaaaaacgc cgcaaagaagaagaagaaaagaaaatcaaagagcaaattgctaaagaaaaagaagatggt gaaaaaatttas 312 <210> 51 0 <211> 312 <212> DNA

<213> Streptococcus eumoniae pn <400> 51 25 atgtcattaacatcaaaacaacgtgccttcctcaacagccaggcacacaccctcaaacct atcatccaaatcgggaaaaatggactcaacgaccaaatcaaaaccagcgtccgtcaagct cttgatgcgcgtgaattaatcaaggttactctcttacaaaa.cacagatgaaaacatccac gaagtagctgaaattttggaagaagaaatcggtgtggatacagtccaaaaaataggacgc atcttgattttgtttaaacaatctagcaagaaagaaaatcgcaagatttctaagaaagtc 0 aaagaaatctas ~ 312 <210> 52 <211> 528 <212> DNA

35 <213> Streptococcus pneumoniae <400> 52 atggcgattgaaaattatataccagattttgctgtggaagcagtctatgatctgacagtc ccaagcctgcaggcgcagggaatcaaggctgttttggtcgatttggataataccctcatt 4O gcttggaacaaccctgatggaacgccagagatgaagcaa'tggctacatgaccttcgggac gcgggtattggcattatcgtagtgtcaaataacaccaaaaaacgcgttcaacgagcagtt gagaaatttgggattgattacgtttactgggccttgaagcccttcacatttggtattgac cgtgctatgaaggaattccactatgacaaaaaggaagtggtcatggttggtgaccagctc atgacagatatacgagcagcccaccgtgcagggattcggtcaattttagtcaaacccttg 4S gtccaacatgactcaatcaaaacgcagattaaccgaactcgtgagcgtcgtgttatgaga aaaatcactgaaaagtacggaccgattacatataaaaaaggaatttaa 528 <210> 53 <211> 1368 SO <212> DNA

<213> Streptococcus pneumoniae <400> 53 atgtttcgaaaaattttaattgccaatcgtggtgaaattgcggttcgtattatccgtgcg SS gcacgtgaattggggattgcgacggtagcggtttattcaactgctgataaggaagctctt catacgctgttggcagatgaagcagtttgtattggtcctggcaaggcaacagagtcttat ctcaatattaatgcagttctatcagctgcagtcttgactgaggcagaagctattcaccct ggttttggatttctcagtgaaaattccaaatttgcgaccatgtgtgaagaaataggtatc300 aagtttatcggtccatctggtcatgttatggatatgatgggggataaaatcaatgcgcgt360 gctcagatgattaaagcaggtgtgcctgttataccaggttcagatggagaagtgcataac420 tctgaagaagctttgattgttgctgaaaaaattggctatcctgttatgctcaaggcttca480 'gcaggtggaggtggtaaagggattcgtaaggttgaaaaaccagatgacctcgtttctgcc540 tttgaaactgcctctagtgaggccaaggccaattatggcaatggtgc~catgtacatagaa600 cgggttatctatccagctcggcacattgaggttcaaatcctaggtgatgagcatggacat660 gtgattcacttgggtgaacgggattgttctcttcaaaggaataaccaaaaggttttggaa720 gaaagtccctcgattgcaatcggaaaaacgctgcgtcatgaaataggtgctgctgctgtt780 1~ cgagcggcag.agtttgttggctatgagaatgcaggaaccattgaatttcttcttgatgaa840 gcaagtagcaatttctatttcatggagatgaatactcgtgttcaggtagaacatccagta900 acagagtttgtttcaggtgttgatatcgttaaggaacagatttgcattgcggcaggtcag960 cctttgtctgttaagcaagaagatattgtcctacgcggtcatgccatcgagtgtcgtatc1020 aatgcagaaaacccagcctttaactttgctccaagtccaggtaagattactaatctctat1080 ctgccaagtggtggagttggcttgcgcgtggattcagcagtttatccaggttataccatt1140 ccgccttattatgatagtatgattgccaaaatcatagtacacggcgaaaatcgttttgac1200 gccttgatgaaaatgcaacgtgccctctatgaattagaaattgaaggagtgcagaccaat1260 gcagatttccagcttgacctcatttcagatcgcaatgtcattgctggggattatgatact1320 tgcttcttgatggaaaccttcttacctaaatatcaagaaaaagaataa 1368 <210> 54 <211> 234 <212> DNA
<213> Streptococcus pneumoniae <400> 54 atgatttaca ,aagtttttta tcaagaaaca aaagaacgta gcccacgccg tgaaacaaca 60 cgcgcgcttt acctagacat egataccagc tcagaacttg agggccgtat cactgctcgc 120 caacttgtcg aagaaaatcg cccagagtac aatatcgaat atatcgaact cttgtctgac 180 ~ aaattgctcg attacgaaaa agaaactggc gccttcgaaa ttacggagtt ctaa 234 <210> 55 <211> 1011 <212> DNA

<213> Streptococcus pneumoniae <400> 55 atgaaggatagatatattttagcatttgagacatcctgtgatgagaccagtgtcgccgtc60 ttgaaaaacgacgatgagctcttgtccaatgtcattgctagtcaaattgagagtcacaaa120 cgttttggtggcgtagtgcccgaagtagccagtcgtcaccatgtcgaggtcattacagcc180 ~tgtatcgaggaggcattggcagaagcagggattaccgaagaggacgtgacagctgttgcg240 gttacctacggaccaggcttggtcggagccttgctagttggtttgtcagctgccaaggcc300 tttgcttgggctcacggacttccactgattcctgttaatcacatggctgggcacctcatg360 gcagctcagagtgtggagcctttggagtttcccttgctagccctcttggtcagcggcgga420 4S cacacagagttggtctatgtttctgaggctggcgattacaagattgttggggagacacga480 gatgacgcggttggcgaggcctatgataaggtcggccgtgtcatgggcttgacctatcct540 gcaggtcgtgagattgacgagctggctcatcaggggcaggatatttatgatttcccccgt600 gccatgattaaggaagataatctggagttttcattctctggtttgaagtcagcctttatc660 aatcttcatcacaatgccgagcaaaagggagaaagcctgtctacagaagatttgtgtgct720 5~ tccttccaagcagcagttatggacattctcatggcaaaaaccaagaaggctttggaggaa780 tatcctgttaaaaccctatttgtggcaggtggtgtggcagccaataaaggtctcagagaa840 cgcttagcagccgaaatcacagatgtcaaggttatcatcccccctctgcgactctgcgga900 gacaatgcaggtatgattgcctatgccagcgtcagcgagtggaacaaagaaaacttcgca960 ggctgggacctcaatgccaaaccaagtcttgcctttgataccatggaataa 1011 <210> 56 <211> 1809 <212> DNA
213> Streptococcus pneumoniae <400> 56 ~S atgtgtggaattgttggt.gttgttggaaacacaaatgcaactgatattttgattcaaggg60 cttgaaaagcttgaataccgtggctatgattctgcgggaatttt~tgtcctagatggtgct120 gataaccatttggtgaaggcggttggtcgtattgcagaattgtctgccaagacagctggt180 gttgagggaacaactggtatcggacatactcgttgggctactcacggaaaaccaactgag240 gacaatgctcacccacaccgctctgagacagaacgttttgtcttggtgcataatggggtg300 attgagaactatcttgaaatcaaggaagaataccttgcaggtcaccacttcaaggggcag360 acagatactgaaatagccgttcatttgattggaaaatttgcggaagaagaagggctctca420 gttcttgaagcctttaaaaaagctcttcatattatccgtggttcatatgcctttgccttg480 attgactctgaaaatccagatgtcatctatgtagcgaaaaacaaatctccacttttgatt540 ggtcttggggaaggctacaatatggtctgctcagatgctatggctatgattcgtgaaacc600 aaccaatacatggaaattcatgaccaagagttggtaatcgtca.aggctgatagcgtggaa660 gttcaagactatgatggtaacagtcgtgaacgtgctagctatactgcggaacttgacttg720 tcagatatcggtaagggaacttatccttactacatgcttaaggaaattgatgagcaacca780 actgttatgcgtaaactcattcaagcctacacggatgatgctggtcaagtagtggttgct840 cctgctatcatta.aggctgttcaagacgcagaccgcatctacatccttgcagctggaaca900 ~ tcttaccatgcaggatttgcttctaagaaaatgttggaagaattgacagatacaccagtt960 gaacttggaatctcatctgagtggggctacggtatgccacttctcagcaagaaaccactc1020 ttcatctttatcagccaatctggtgaaacagcggatagtcgtcaagttttggtcaaggct1080 aatgaaatgggaattccaagcttaacagtgacaaatgttccaggttcaaccctctcacgt1140 gaagccaactataccatgctccttcacgcaggacctgaaattgccgtggcatcaactaaa1200 ~5 gcctatacagCCJCaaatCgCagCCCttgCCttccttgcaaaagcagtcggagaagcaaat1260 ggtaatgctaaagcgcaagcctttgacctggttcatgaattgtcaatcgtagctcagtct1320 attgaatcaactctttcagagaaagaaaccattgaagccaaggttcgtgaacttcttgaa1380 acaactcgtaacgccttttacatcggacgtggtcaagattactacgtagccatggaagca1440 agtctcaaactcaaagagatttcttatatccagtgtgaaggttttgcggcaggagaactc1500 ~ aagcacggaaccattgccttgattgaagaaggaacgcctgtt.ttggctctcttgtcagat1560 ccagttcttgccaaccatactcgtggaaatatccaagaggtcgcagcccgggtgccaaa1620 t gtcctcactatcgcagaagagaatgtagccaaagataccgacgatatcgtccttacgacc1680 gtacatccatacctctcaccaatttcaatggtcgtaccaacgcaattagtcgcttacttt1740 gcaaccctccaccgtggcctcgatgtggacaaaccacgtaaccttgccaagtcagtaacg1800 35 gtagaataa 1809 <210> 57 <211> 723 <212> DNA

~ <213> Streptococcus eumoniae pn <400> 57 atgatacgta tcgaaaatct cagtgtctcc tacaaagaaa cgttggcact taaggatatt 60 tcactagtgc tccatggacc aacaattacc ggcatcattg gtccaaacgg cgctgggaaa 120 4$ tcaacactat taaaaggtat gctgggaatt atcccacatc aaggtcaggc atttctcgat 180 gacaaggaag ttaaaaaatc cttacaccga attgcctatg tcgaacaaaa aatcaatatc 240 gactacaact ttcccatcaa ggtcaaggaa tgcgtctcgt taggactatt tccctctatt 300 cctctctttc gaagtttaaa ggctaaacat tggaagaaag tgcaagaggc ccttgaaatc 360 gtcggcctag ctgactacgc tgaacgtcaa attagtcaac tgtctggagg tcaattccag 420 50 cgggtcttga ttgccagatg tttggtgcag gaagccgact atatcctctt ggatgaaccc 480 tttgctggga ttgactctgt cagtgaggaa atcatcatga atacgctgag agatttgaaa 540 aaagctggga agacggttct catcgttcac cacgacctca gcaagattcc ccactacttc 600 gatcaagtct tacttgtcaa tcgagaagtg attgcctttg gtccaacaaa agaaactttt 660 accgaaacca atctaaaaga agcttacggt aatcaactct ttttcaatgg aggtgaccta 720 SS tga 723 <210> 58 <211> 2223 <212> DNA
<213> Streptococcus pneumoniae <400> 58 atgccgaaagaagtgaatttaacaggcgaagaagttgtcgctttaaccaaagaatattta60 acggaagaggatgttcattttgtccataaggccttggtctatgctgttgaatgccacagt120 ggtcaatatcgcaaatcaggcgagccttatatcattcaccctatccaagtggcaggtatt180 ttagctaagctaaagctggatgctgtaacagtagcttgtggattcttgcatgatgtggtg240 1~ gaagatacagatgcgaccttggacgatttggaaagagagtttggtcctgatgtgcgggtg300 attgttgacggagttaccaagcttggcaaggtcgagtacaaatcgatcgaggagcaatta360 gcggaaaatcatcgcaagatgctcatggccatgtctgaggacatccgcgttattttggtc420 aaactgtctgaccgcttgcacaatatgcggaccctgaaacatcttcgaaaagacaagcag480 gagcgtatttccaaagaaaccatggaaatctatgccccacttgcccatcgtttggggatt540 15 tccagtgtcaaatgggaattagaagacttgtctttccgttatctcaatccaacggagttt600 tacaagattacccatatgatgaaggaaaagcgcagggagcgtgaggccttggtggatgag660 gtagtcacaaaattagaggagtatacgacagaacgtcacttgaaagggaagatttatggt720 cgtcccaagcatatttactcaattttccgcaaaatgcaggacaagagaaaacggtttgag780 gaaatctatgatctgattgctattcgttgtattttagatacccaaagtgatgtttatgcc840 ~ atgcttggttacgtgcatgaattttggaaaccgatgccaggtcgcttcaaagactatatt900 gccaaccgcaaggccaatggttatcagtctatccatacgactgtttatggaccaaaaggg960 ccgattgaattccagattcgaaccaaggaaatgcacgaggtggctgagtacggggttgcg1020 gctcactgggcttataagaaaggtataaaggggcaagttaacagcaaggaatcagctatt1080 ggaatgaactggatcaaggagatgatggagctccaagaccaggctgatgatgctaaggaa1140 25 tttgtggactctgttaaggaaaactatctggctgaggagatttacgtttttaccccagat1200 ggagctgtccgttcccttcccaaagattcaggaccgattgattttgcctacgaaatccat1260 accaaggtcggtgaaaaagcaactggtgccaaggtcaatggccgcatggttccactgaca1320 accaagttaaagacaggggatcaggttgaaattatcgccaacccgaactcctttggacct1380 agccgtgactggctcaatatggtcaagactagcaaggcgcgcaataagattcgccagttc1440 ~ tttaaaaaccaagataaggaattgtctgtcaacaagggtcgtgagatgctgatggctcag1500 ttccaagaaaatggctatgtggcaaataaatttatggacaagcgccacatggatcaagtt1560 ctgcaaaagaccagttacaagacagaagactccctctttgcggccattggttttggggaa1620 atcggtgcgattaccgtctttaaccgtctgactgaaaaggaacgccgtgaggaagagcgt1680 gccaaggccaaggctgaggcagaggagcttgtcaaaggtggcgaggtcaaggttgaaaat1740 35 aaagaaactctcaaggtcaagcatgaggggggagtggttattgaaggtgcttctggtctc1800 ctagtgcggattgctaagtgttgtaaccccgtgcctggtgacgatattgttggctacatt.1860 accaagggtcgtggtgtggctattcaccgtgtggactgtatgaacctgcgtgcccaagaa1920 aactacgagcaacgtctccttgatgtggaatgggaagaccagtactctagctcaaataag1980 gagtatctggcccatatcgatatctacggtctcaaccgtacaggactgttgaacgatgta2040 4~ ctgcaagttctttcaaatacaaccaagaatatttcaacggtcaatgcccaaccaaccaag2100 gatatgaagtttgctaatatccatgtgtccttcggtattgccaacctctctacactgacc2160 acggttgtcgataaaattaagagtgtgccagaagtttactctgtcaaacggaccaacggc2220 tag 2223 45 <210> 59 <211> 1479 <212> DNA
<213> Streptococcus pneumoniae 5~ <400> 59 atgtctaatt gggacactaa atttttgaaa aaaggtttta cctttgatga tgtattgctt 60 attccagctg aaagtcatgt gttgcctaac gatgcagatt taacaactaa attggcagat 120 aatttgactt taaatatccc aattattacc gctgccatgg acacagttac agagagtcaa 180 atggccattg ctattgctcg tgcaggcggt ctcggagtta tccataaaaa catgtcaatt 240 SS gctcaacaag cagacgaggt tcgtaaggta aaacgttctg aaaatggagt tattattgat 300 ccgttcttct tgacgcctga acatacaatt gctgaagcag atgagcttat gggtcgttac 360 cgcatcagtg gtgttccagt tgttgaaaca cttgaaaatc gtaaattggt tggtattttg 420 acaaaccgag atcttcgttt tatttcagat tataatcaac caatttcaaa ccatatgact 480 agtgaaaatc ttgttactgc tcctgtgggt acggatcttg caacggctga gagtattctt 540 caagagcatc gtattgaaaa acttccgttg gtcgatgaag aaggcagtct, ttctggtttg 600 atcactatca aagatattga aaaagttatt gagtttccaa atgcggctaa agatgagttt 660 ggtcgtcttc tagttgcagg tgcagtaggt gttacttcag atacatttga acgtgcagag 720 gctctttttg aggcaggagc ggatgcgatt gttattgata ctgcacatgg tcattctgca 780 ggtgtcttgc gtaaaattgc cgagattcgt gctcatttcc cagatcggac tttgattgct 840 ggaaatattg ctactgctga aggtgcacgt gccctttatg aagcgggtgt agacgttgtt 900 aaggttggta.ttggaccagg ttctatctgt actactcgtg tgattgctgg tgttggtgtt 960 1~ ccgcaagtaa cagctatcta cgatgctgca gctgttgcgc gcgaatatgg taaaacgatt 1020 attgctgacg gtgggatcaa gtattctgga gatattgtaa aagcacttgc tgcaggtgga 1080 aatgctgtta tgcttggatc tatgtttgct ggaactgatg aagctccagg cgaaactgaa 1140 atcttccaag gacgtaaatt caagacttac cgtggtatgg gatcaattgc tgctatgaag 1200 aaaggttcaa gcgaccgtta tttccaaggt tctgtcaatg aagcaaacaa gcttgttcca 1260 IS gaaggaattg aaggtcgtgt tgcttataaa ggagcggcag ctgatattgt tttccaaatg 1320 attggtggta ttcgctctgg tatgggttac tgtggtgcag ctaaccttaa agaactacac 1380 gataatgctc aatttattga aatgtctggt gctggtttga aagaaagcca tcctcatgat 1440 gtgcaaatta ctaatgaggc accaaattat tctatgtaa 1479 20 <210> 60 <211> 1947 <212> DNA
<213> Streptococcus pneumoniae 25 <400> 60 atgacagaagaaatcaaaaatctgcaggcacaggattatgatgccagtcaaattcaagtt60 ttagagggcttagaggctgttcgtatgcgtccagggatgtacattggatcaacctcaaaa120 gaaggtcttcaccatctagtctgggaaattgttgataactcaattgacgaggccttggca180 ggatttgccagccatattcaagtttttattgagccagatgattcgattactgttgtggat240 ~ gatgggcgtggtatcccagtcgatattcaggaaaaaacag.gccgtcctgctgttgagacc300 gtctttacagtccttcacgctggaggaaagttcggcggtggtggatacaaggtttcaggt360 ggtcttcacggggtggggtcgtcagtagttaatgccctttccactcaattagacgttcat420 gttcacaaaaatggtaagattcattaccaagaataccgtcgtggtcatgttgtcgcagat480 cttgaaatagttggagatacggataaaacaggaacaactgttcacttcacaccggaccca540 35 aaaatcttcactgaaacaacaatctttgattttgataaattaaataaacggattcaagag600 ttggcctttctaaatcgcggtcttcaaatttcaattacagataagcgccaaggtttggaa660 caaaccaagcattatcattatgaaggtgggattgctagttacgttgaatatatcaacgag720 aacaaggatgtaatctttgatacaccaatctatacagacggtgagatggatgatatcaca780 gttgaggtagccatgcagtacacaactggttaccatgaaaatgtcatgagtttcgccaat840 0~ aatattcatacacatgaaggtggaacgcatgaacaaggtttccgtacagccttgacacgt900 gttatcaatgattatgctcgtaaaaataagttactgaaagacaatgaagacaacctaaca960 ggggaagatgttcgcgaaggcttaactgcagttatctcagttaaacacccaaatccacag1020 tttgaaggacaaaccaagaccaaattgggaaatagcgaagtggtcaagattaccaatcgc1080 ctcttcagtgaagccttctccgatttcctcatggaaaatccacagattgccaaacgtatc1140 4S g.tggaaaaagggattttagctgccaaggctcgtgtggctgccaagcgtgcgcgtgaagtc1200 acacgtaaaaaatctggtttggaaatttccaaccttccagggaaactagcagactgttct1260 tctaataaccctgctgaaacagaactcttcatcgtcgaaggagactcagctggtggatca1320 gccaaatctggtcgtaaccgtgagtttcaggct'atccttccaattcgcggtaagattttg1380 aacgttgaaaaagcaagtatggataagattctagctaacgaagaaattcgtagtcttttc1440 5~ acagccatgggaacaggatttggcgcagaatttgatgtttcgaaagcccgttaccaaaaa1500 ctcgttttgatgaccgatgccgatgtcgatggagcccacattcgtacccttcttttaacc1560 ttgatttatcgttatatgaaaccaatcctagaagctggttatgtttatattgcccaacca1620 ccaatctatggtgtcaaggttggaagcgagattaaagaatatatccagccgggtgcagat1680 caagaaatcaaactccaagaagctttagcccgttatagtgaaggtcgtaccaaaccgact1740 SS attcagcgttataaggggctaggtgaaatg~gacgatcatcagctgtgggaaacaaccatg1800 gatcccgaacatcgcttgatggctagagtttctgtagatgatgctgcagaagcagataaa1860 atctttgatatgttgatgggggatcgagtagagcctcgtcgtgagtttatcgaagaaaat1920 gctgtctatagta.cacttgatgtctaa 1947 <210> 61 <211> 267 $ <212> DNA

<213> Streptococcus pneumoniae <400> 61 atgggatttactgaagaaacagtacgttttaaattggacgattccaataaaaaagaaatt60 10'agcgaaactttgacagatgtttatgcttcgttgaacgataagggttacaacccaattaac120 caaatcgtaggttacgtattgagtggagaccctgcctacgttcctcgttataataatgca180 cgaaatcaaatccgtaagtatgagcgtgatgaaatcgttgaggaattggttcgctactac240 ctcaaaggacaaggagtcgatctataa 267 15 <210> 62 <211> 597 <212> DNA

<213> Streptococcus pneumoniae 0 <400> 62.

atggtcaactatccacataaagtttcatcacaaaaaagacaaacatctctttctcaaccc60 aaaaatttcgcaaatcgaggaatgtcttttgaaaagatgatcaatgctaccaacgactac120 tatttgtctcagggcttggctgttatacataagaaaccaactcctattcaaatcgtacaa180 gtggactatccacaacgaagtcgtgccaagattgttgaagcctattttcgacaagcttca240 25 acgacggactattctggcgtttataatggatattacatcgactttgaagtcaaggaaaca300 aaacaaaaacgtgcgattccgatgaaaaattttcatccacatcagattcagcatatggaa360 caagtccttgcccaacaaggaatctgctttgtccttcttcacttttcttctcagcaagaa420 acctacttattgccggcattcgatttgattcgcttctatcatcaagataagggacaaaaa480 tcaatgccacttgaatatattcgagaatatggatatgaaatcaaggctggtgccttccct540 30 caaattccttatctcaatgttatcaaagaacatttattaggtggtaaaacaagatga 597 <210> 63 <211> 867 <212> DNA

35 <213> Streptococcus eumoniae pn <400> 63 atggctctatttagtaaaaaagataagtatattcgaatcaatcccaatcgttcggttagg60 gaaaaacctcaagctaagccagaggttccagatgaattattttcccagtgtccaggctgt120 40 aagcataccatctatcagaaggatctgggaagtgaacgtatctgtccgcactgtagctat180 acctttcgtatttctgcccaagaacgcttg,gctt~tgacgattgatatgggaaccttcaaa240 gaattgtttacagggattgaaagcaaggatcccttgcatttccctggttaccaaaagaaa300 ctggcatctatgcgtgaaaaaacaggtctgcatgaagccgttgtgacaggaactgctctt360 attaaaggtcagactgtggctcttgggattatggattctaactttatcatggcttctatg420 4S ggtacggttgtaggtgaaaaaatcactcgtttgtttgagtatgcgactgtcgaaaaattg480 ccagttgtcctattcacagcctctggtggagcccgtatgcaggaaggaatcatgagtct.c540 atgcagatggctaagatctctgcggcggttaaacgccattcaaatgctggtctcttttac600 ctgaccattttgacagatccaacgactggtggtgtgacagcttctttcgctatggaaggc660 gatatcattctggctgaaccacagagcttggttggttttgctggacgtcgtgtgattgaa720 50 aatacggttcgtgaaagct.tgcctgaggatttccaaaaggcagaattcctattagaacat780 ggctttgtggatgctattgtcaaaagaagagacttaccagatacgattgctagcctagtc840 agattgcatggagggagtcctagatga ~ 867 <210> 64 SS <211> 420 <212> DNA

<213> Streptococcus pneumoniae <400> 64 atgagaatta tgggattgga cgtcggttca aaaacggtag gggtggcgat tagcgatccg 60 cttggtttta cagctcaagg gcttgaaatc atccagataa atgaagaaca aggccaattt 120 ggttctgacc gcgttaagga attggttgat acttacaagg tggaacgatt tgtagtgggc 180 ttgcctaaaa acatgaacaa tacaagtgga ccgcgcgtag aagctagtca agcatacgga 240 gcaaagctag aagagttttt tggtttacca gtagactatc aggatgaacg cttgacaaca 300 gtggctgctg agcgcatgtt gattgaacaa gcagatatca gtcgcaataa gcgcaagaaa 360 gtcattgata agttagcagc tcagctgatt ttacaaaatt atttagatag aaaattttaa 420 <210> 65 <211> 1197 <212> DNA
<213> Streptococcus pneumoniae <400> 65 atggcaaaacttactgttaaagacgttgacttgaaaggtaaaaaagtcctcgttcgtgtt60 gacttcaacgtaccattgaaagatggcgtaatcactaacgataaccgtatcacagcagct120 cttccaactattaagtacatcatcgaacaaggtggacgtgcaattcttttctctcacctt180 ggacgtgtgaaagaagaagctgataaagctggtaaatcacttgctcctgtagcagcagac240 ttggcagcaaaacttggtcaagatgttgttttcccaggtgtcactcgtggtgctgaattg300 gaagcggcaatcaacgctcttgaagatggacaagttctcttggttgaaaacactcgttac360 gaagatgttgacggcaagaaagaatctaaaaacgatcctgaacttggtaaatactgggca420 tcacttggagatggt'atcttcgtaaacgatgcattcggtacagctcaccgtgcacacgca480 S tctaacgttggtatctcagcaaacgttgaaaaagcagttgctggtttccttcttgaaaac540 gaaattgcctacatccaagaagcagttgaaactccagaacgtccattcgtggctatcctt600 ggtggttcaaaagtttcagacaagatcggtgttatcgaaa~acttgcttgaaaaagctgat660 aaagtccttatcggtggtgggatgacttacacattctacaaagcacaaggtatcgaaatc720 ggtaactcacttgtagaagaagacaaattggatgttgcga.aagctcttcttgaaaaagca780 aatggtaaattgatcttgccagttgactcaaaagaagctaacgcatttgctggttacact840 gaagtgcgtgacactgaaggtgaagcagtttctgaaggcttccttggtcttgacatcggt900 ccaaaatctatcgccaaatttgacgaagctttgactggtgccaaaacagttgtatggaac960 ggacctatgggtgtatttgaaaacccagatttccaagctggtacaatcggtgtgatggac1020 gctatcgtgaaacaaccaggagttaaatcaatcatcggtggtggtgactcagctgccgca1080 gcgattaaccttggccgtgcagacaagttctcatggattagtacgggtggtggagcatca1140 atggaacttcttgaaggtaaggttcttccacaacttgcagccttgacagaaaaataa 1197 <210> 66 <211> 498 <212> DNA

<213> Streptococcus pneumoniae <400> 66 atgttaaaatcagaaaaacaatcacgttatcaaatgttaaatgaagaattgtccttccta60 4$ ttggaaggcgaaaccaatgttttggctaatctttccaacgccagtgctctcataaaatca120 cgttttcctaataccgtatttgcaggcttttatttgttcgatggaaaggaattggtttta180 ggccccttccaaggaggtgtttcctgcatccgtattgcactaggcaagggtgtttgtggt240 gaggcagctcactttcaggaaactgttattgttggagatgtgacgacctatctcaactat300 atttcttgtgatagtctagctaaaagtgaaattgtggtgccgatgatgaagaatggtcag360 ttacttggagttctggatctggattcttcagagattgaggattacgatgctatggatcga420 gattatttggaacaatttgtcgctattttgcttgaaaagacagcatgggactttacgatg480 tttgaggaaaaatcttaa 498 <210> 67 SS <211> 630 <212> DNA

<213> Streptococcus eumoniae pn <400> 67 atgacaatcgaactattgactccctttaccaaggtagagttggagccagaaatcaaggag aaaaaacgca'aacaagttgggattttaggggggaattttaaccctgttcacaatgcccat S ctcattgttgcggatcaagtacggcaacagttgggactggatcaagttctgctcatgcct gaataccaacctcctcacgttgataaaaaggaaaccatccctgaacaccatcgtctcaag atgcttgagttggcaattgagggaattgacggcctagtcattgaaaccattgagttggag cgcaagggtatttcctacacctacgacaccatgaagattttgacagagaagaatccagat acggattattactttatcatcggtgccgacatggttgactatctgcctaagtggtaccga attgatgaactggttgacatggttcagtttgtgggggttcagcgtccacgctacaaggta gggacttcctatccagttat.ctgggtggacgtaccgctcatggatatctcgtccagcatg gtgcgtgccttccttgcccaaggtcggaaacccaactttctcctacctcagccagtgcta gactacatcgagaaggaggggctctactga ~ 630 IS <210> 68 <211> 768 <212> DNA

<213> Streptococcus pneumoniae <400> 6s atgaatattgcaaaaatagtcagagaagcgcgtgagcagagtcgcttgacaaccttggac tttgcgacaggcatttttgatgaatttatccaattacatggtgaccgttcttttcgtgat gatggtgcag'ttgttggtggtattggttggcttggagaccaagctgtaacagtggttggt atccaaaaaggcaagagtttgcaagacaacctcaaacggaattttggccaaccacatcca 2S gaaggctaccgaaaggcactgcggttgatgaaacaggctgagaaatttggccgtccagtt gtgacctttatcaatacagcaggtgcttatcctggtgtcggagcggaagaacgtggtcaa ggggaagctattgctcgcaatctcatggaaatgagtgacctgaaagttcctattatcgcc attattatcggtgaaggtggttcaggcggggctctggctctagctgtcgcggaccgtgtc tggatgctggaaaattctatctatgccattctcagtccagaaggctttgcttccatttta tggaaggacggtactcgcgccatggaagcagcagaactgatgaaaatcacttcgcatgaa ctgttagaaatggacgtggtggataaggtgatttctgaagtaggactttctagtaaagaa ctgattaagagtgtcaaaaaagaactccaaacggagctggctagactttcacaaaaaccg ctagaagagttgctggaagaacgctatcaacgatttagaaaatactaa 768 3S <210> 69 <211> 510 <212> DNA

<213> Streptococcus pneumoniae 0 <400> 69 .

atgattataaaagtagaaatggcagatgttgaggtgttggctaaaattgccaaacaaacc tttcgtgaaacctttgcgtatgataatacggaagagcagttacaggaatactttgaagag gcttatagtctgaaaactttgtcaactgagttgggaaatcctgactctgaaacctatttc attatgcatgaggaggagatagctggttttctcaaagtcaactggggaagtgctcaaact 4S gagagagaattagaggacgcttttgaaattcaacgcctctatgtgctacaaaaattccaa ggatttggactaggtaagcaactgtttgaattcgcacttgaacttgctacaaaaaatagt ttttcttgggcttggctaggtgtttgggagcataatacaaaagctcaagccttttataat cgatatggttttgaaaaatttagccaacatcattttatggttggtcaaaaagtagatacg gattggttaotgagaaagaaattaaggtaa ~ ' 510 <210> 70 <211> 1590 <212> DNA
<213> Streptococcus pneumoniae <400> 70 -atgttacggg.ggactgcttt gctaacggct agtaacttta tcagtcgcct actcggggct 60 gtttacattatcccttggtacatctggatgggggcttatgcagctaaggcaaatggtctc120 tttaccatgggttacactatctatgcttggttcttgttggtttcaacagcggggattcca180 gttgcggtggccaagcaagttgccaagtataataccatgcgagaagaagagcatagcttt240 gccctgattcggagcttcttaggctttatgacaggactaggcctggtttttgctttagtc300 S ttgtatgtctttgctccttggctagcagacttgtctggcgtgggcaaagacttgatccca360 atcatgcaaagcttggcttggggagtcttgattttcccgtctatgagtgttatccgagga420 tttttccaagggatgaataacctcaaaccctatgccatgagccaaattgctgagcaggtc480 attcgtgttatctggatgctcctagcaacctttatcattatgaagctcggttcaggagat540 tatctagcagccgttacccaatcaacctttgctgcctttg.tcggtatggtagccagtttt600 gcagtcttgatttatttccttgcccaagaaagttcactcaaaagagtctttgaaacagga660 gataagattaacagtaagcgtctcttggttgat~accattaaggaagccattccttttatc720 ctgacagggtctgccatccagatcttccagattttggatcagctgacctttatcaatagt780 atgagctggtttaccaactacagcaatgaggacttggttgtcatgttttcttatttctca840 gccaatcctaataaaatcacgatgattttgatttctgtaggggtttcgattgggagtgtt900 IS ggtttgccacttttgacggaaaactatgtcaagggggacttgaaagcggcttctcgtctc960 gttcaggacagtctcaccctactctttatgttcttgctaccagcaacggttggagtggtt1020 atggtaggagaacctctttatacggtcttctatggtaagccagatagtttggctctgggc1080 ttatttgtctttgcagttttgcagtctattattttaggcttgtacatggtcttgtctcca1140 atgcttcaggccatgttccgcaaccgcaaggccgttctctattttatctatggttctatt1200 2~ gccaagctagtcttgcaactacctaccatcgccctcttccacagttatggtcctttgatt1260 tcaacaaccattgctctcatcattcctaacgtcttgatgtatcgggatatttgtaaagta1320 actggtgtcaagogcaaggtgattttgaagcgaaccattttaatcagtttgctgacccta1380 gtcatgtttctgttaataggaaccatccagtggctgttaggatttttcttccaaccaagt1440 ggacgtttgtggagcttcttttatgtagctcttgtcggtgccatggggggtggactttat1500 ~S atggttatgagtctgcgtacctatttattagataaggtaataggaaaagcccaagcagat1560 .cgcctgcgagcaaaatttaagctttcgtaa 1590 <210> 71 <211> 468 ~ <212> DNA

<213> Streptococcus pneumoniae <400> 71 atgtcagataagattggcttattcacaggctcatttgatccgatgacaaatgggcatctg 3S gatatcattgaacgggcgagcagactctttgataagctctatgtcggtattttttttaat ccccacaaacaaggatttcttcctatcgaaaatcgtaaacgggggctagaaaaggctttg ggacatctggaaaatgttgaagtcgtggcttctcatgatgaattggtggtcgatgttgca aaaagattgggtgctacttgtctagtgcgtggtttgaggaatgcgtcggatttgcaatat gaagccagttttgattactacaatcatcagctgtcttctgatatagagactatttattta ~ catagtcgacctgaacatctctatatcagttcatcaggcgttagagagcttttgaagttt ggtcaggatattgcctgctatgttcccgagagtatttggaggaaataa 468 <21.0> ' <211> 432 5 <212> DNA

<213> Streptococcus pneumoniae <400> 72 atgacgattttgtttgtggttatcagtgcttcctttctgtatatggtttctcttagcatg 5~ aaaccctatcaaacagctaaaagtgaaggagaaaaattagctcagcagtatgcaggatta gagcaggccgatcaggttgatttatacaatggcttggaatcttattacagcgttcttggt ' cgtaataaacagcaagaagcacttgctgttctgattggaaaagatgatcataagatttac gtttatcagctaaatcagggtgtttcacaagaaaaagcagaaacggtttctaaggaaaag ggagctggcgaaattgacaagattatctttggtcgttatcaagataagccaatctgggaa SS gtcaagtcaggatctgatttttatctagtagattttgaaacaggagcattggtcaacaag gagggcctatga 432 <210> 73 <211> 732 <212> DNA
<213> Streptococcus pneumoniae '<400> 73 atgattgata ttcattcgca cattgtcttt gatgtagatg atggtcccaa gtcaagagag 60 gaaagtaagg ctctcttgac agaagcctac aggcaggggg tgcgaaccat tgtctctacc 120 tctcaccgtc gcaagggcat gtttgaaact ccagaagaga agatagcaga aaactttctt 180 caggttcggg aaatagctaa ggaagtcgcg agtgacttgg tcattgctta tggggctgaa 240 atttactaca cgccagatgt tttggataag ctggaaaaca atcggattcc gaccctcaat 300 aatagtcgtt atgccttgat agagtttagt atgaacactc cttatcgcga tatttatagt 360 gccttgaata aaatattgat gttgggaatt actcccgtca ttgcccacat agagcgctat 420 gatgttcttg aaaataatga aaaacgcgtt cgagagctga tcgatatggg ctgttacacg 480 IS caaataaata gttcacatgt cctcaaatcc aaactttttg gagaacctta taaattcatg 540 aaaaaaagag cgcagtattt cttggagcgt gatttggttc atatcattgc aagtgatatg 600 cataatgtgg acggcagacc cccccatatg gtagaagcat atgaccttgt ttcccaaaaa 660 tacggagaag cgaaggctca ggaacttttt atagacaatc ctcgaaaaat tgtaatggat 720 caactaattt ag 732 2~
<210> 74 <211> 927 <212> DNA
<2l3> Streptococcus pneumoniae <400> 74 atgtctacaatcgataaagaaaaatttcagtttgtaaaacgtgacgattttgcctctgaa60 actattgatgcgccagcatattcttactggaaatcagtgtttaaacaatttatgaagaaa120 aaattaactgtagtcatgttgggaatcttggtagccatcattttgataagtttcatctac180 3o ccaatgttttctaagtttgatttcaatgatgtcagcaaggtaaacgactttagtgttcgt240 tatatcaagccaaatgcggagcattggttcggtactgacagtaacggtaaatcgctcttt300 gacggtgtctggttcggagctcgtaactccatcctcatttctgtgattgcgacagtgatt360 aacttggttatcggtgtttttgtcggtggtatttggggtatttcaaaatcagttgaccgt420 gtcatgatggaagtttacaacgtcatctcaaacatcccacctcttttgattgttattgtc480 3S ttgacttactcaatcggagctggattctggaatctgatttttgccatgagcgtaacaaca540 tggattggtattgccttcatgatccgtgtgcaaatcttgcgctatcgtgacttggaatac600 aacttggcgtcacgtactttgggaacaccaaccttgaagattgttgccaaaaatatcatg.660 cctcaattggtatct tgtgacaaccatgactcaaatgcttccaagctttatctca720 gttat tacgaagccttcttgtctttcttcggtcttggattaccgattacagtgccaagtttgggt780 40 cgtttgatttcggattattcacaaaacgtaacaaccaatgcttacttgttctggattcca840 ttgacaacccttgtcttggtatccttgtcccttttcgtagttggtcaaaacttagcggat900 gctagtgatccacgtacacatagatag 927 <210> 75 45 <211> 234 <212> DNA

<213> Streptococcus pneumoniae <400> 75 5~ atgtataacctattattaaccattttattagtattatctgttgtgattgtgattgcaatt60 ttcatgcaaccaaccaaaaaccaatccagcaatgtatttgatgccagttcaggtgatttg120 tttgaacgcagtaaagctcgcggttttgaagctgtaatgcagcgtttgacagggatttta180 gtctttttctggctagccattgccttagcattgacggtattatcaagtagataa 234 SS <210> 76 <211> 1110 <212> DNA

<213> Streptococcus pneumoniae <400> 76 atgtttcgtagaaataaattatttttttggaccacagaaattttactcttaaccatcatc60 S ttttacctatggagacagatgggatctttgattaacccttttgttagcgtgcttaataca120 attatgattccatttttattagggggctttctttattatttgacaaaccctattgttact180 ~

ttcttaaataaagtctgtaaactcaatcgtttgcttggtattttaattaccttgtgtact240 ttggtctggggaatggtcataggtgttgtctatctcttacctattttgattaatcagtta300 tctagtttgattatatctagtcaaactatttatagtcgagtacaagacttaatcatagac360 ttatctaattatcctgcgctccagaatttggatgtagaagctacaattcagcagttaaac420 ttatcctatgttgatattcttcaaaatatcctaaatagcgtatcaaatagtgtggggagc480 gtcttgtcagctcttatcagtactgttttgattttgattatgactccagtttttttggtt540 tatttcttattagatggacataaattcttgcccatgcttgaaagaacgattctaaagagg600 gatcgcttgcatattgcaggcttattaaagaatttaaatgcgacgattgctcgctatatt660 IS agtggagtttcgattgacgcaatcattataggttgtttggcttatattggctatagtatt720 attggtttaaaatatgctttagtttttgccattttttctggtgtagccaatttaattcct780 tatgtggggccaagtattggtttgattcctatgatcatcgcaaatatattcactgtaccc840 catagactgctgattgcagtgatttatatgcttgttgttcagcaggtagatggcaatatc900 ttatatcctcgaattgtaggaagtgttatgaaggttcatccaatcacgattttagtttta960 cttttgttgtcaagcaatatctatggtgtagttggaatgattgtcgcagtgccaacctat1020 tctatcttgaaagaaatttctaagttcttatcccgtttgtatgaaaatcataaaataatg1080 aaagaacgagaaagagaatt~agctaagtaa 1110 <210> 77 <211> 1356 <212> DNA

<213> Streptococcus , pneumoniae <400> 77 atgtatcaagcactttatcgaaaatatagaagtcaaaacttctcccagttagttggtcaa60 gaagttgtggctaagactcttaaacaagcggtggagcaagagaaaataagtcacgcttat120 cttttttctggtcctcgtggaacgggaaaaaccagtgttgctaaaatctttgccaaggct180 atgaactgtcccaatcaagtgggtggcgaaccttgcaataactgctatatttgtcaagca240 gtgacggacggtagtttagaagatgtcattgaaatggatgcagcttctaataatggggta300 gatgaaattcgcgaaattcgtgataaatctacctatgcgcctagccttgctcgttataag360 gtttatatcatagatgaggttcacatgctgtctacaggggcttttaatgccctcctaaag420 acgctggaagaaccaacacagaatgtagtctttattttggccactactgaattgcacaag480 attcctgctactattctatcccgtgtgcaacgttttgagtttaaatcaattaagacacag540 gatattaaggaacatattcactatatcttagaaaaagaaaatatcagttctgaaccagag600 gctgtggaaatcattgccagacgggcggaaggtggaatgcgggacgccttgtctattttg660 gatcaagccctgagtttgacacagggaaatgagctgacgactgctatctctgaagaaatt720 actggcaccattagcctatcagcctt.ggatgattatgtggcggccttgtctcaacaggat780 gttcccaaag.ctttgtcttgcttgaatcttctttttgacaatggtaagagcatgactcgt840 tttgtgaccgatcttttgcactatttaagagacttgttaattgttcaaacagggggagaa900 4S aatactcatcatagttcagtctttgtagaaaatttggcacttcctcaaaaaaatctgttt960 gaaatgattcgcttagcaacagtgaatttagcagatattaagtctagtttgcagcccaag1020 atttatgctgaaatgatgaccgtccgtttggcggaaatcaagcccgaaccagctctatca1080 ggagcggttgaaaatgaaattgctacgctgagacaggaagttgcccgtctcaaacaagag1140 ctttctaatgcaggtgcggttcctaaacaagttgcaccagctcctagtcgaccagctacg1200 ggcaaaacagtctatcgtgtcgatcgcaataaagtgcaatctatcttacaagaggccgtc1.260 gaaaatcctgatttaacacgtcaaaatctaattcgtttgcagaatgcatggggagaggta1320 attgaaagtctaggtgggccggacaagctctgctag 1356 <2l0> 78 <211> 1989 <.212>
DNA

<213> Streptococcus pneumoniae <400> 78 atgtttcgat taaccaataagttagcggtatcgaacttgattaaaaaccgcaaactctac60 tatccttttg cgctggctgttctcttggcagtcactctcacctatctcttttactctcta120 accttcaatc ctaagattgcggaaatccgtggaggaacaaccattcaggctacacttgga180 tttggtatgt ttgtcgtcacccttgcgtcagccattatcgttctctatgccaatagtttt240 gtcatgaaga aacgttccaaggaactaggaatttatggcatgttgggcttggagaagcgt300 catcttatca gtatgacctttaaggagttagtggtatttgggattctaactgttggagcg360 ggtatcggta ttggagccttgtttgacaagttaattttcgctttcctgctcaaactaatg4'20 1oaaattgaagg ttgagctggttgctaccttccagacgaaagttgtcattacagtgcttgtt480 gtcttcggtt tgattttcctaggcctcatgttcctgaatgcccttcgaatcgcccgtatg540 aatgccctcc agctctctcgtgagaaagctagtggagagaaaaaaggtcgcttccttcct600 ctccaaacca t'tcttggttccataagtttaggaattggctattatcttgcccttacggta660 aaagatcctc ttacagccttaacaaccttcttcatagctgttttactggttatctttggg720 ISacttatctct tgtttaatgcagggattaccgttttcctccaaatcttaaagaaaaataag780 aaatactatt accaaccaaataacctcatatctgtttctaacttgattttccgtatgaag840 aaaaatgcag ttggactagcaactatcgctattttgtcaacaatggttttggtaaccatg900 tcagcagcga caagcattttcaattccgcagaatcctttaaaaaagttctaaatcctcat960 gattttgggg tttcaggacaaaatgttgaaaaagaagatttggacaaactcttgagccag1020 tttgcaagtg acaatggttataagattaaagaaaaagaagtgtttcgttacacttacttt1080 ggtgttgcga accaagaaggaaataagttaaccttttttgaaaaaggacaaaatcgtgtc1140 caacccacaa cagttttcatggtatttgaccaaaaagattatgaaaatatgactggtcaa1200 aaactgtctc ~tatcaggaaatgaggtcggtctctttgccaaaaatgacggactgaaagga1260 cagaaaactc taattctgaatgatcatcaattttctgtaaaagaagaatttaataaagat1320 ~Stttattgtca accatgtcccaaatcagtttaatattttgactgctgattacaattacctt1380 gttgtacctg atttacaagcctttttgaaccaattcccagattcggatatctataat 1440 cag ttttacggtg gtatgaatgtaaatgtcagtgaagaagaacaactcaaggtcgctgaggag1500 tatgaaaact acctcaatcaatttaatgctcaattagacacagaaggtagctatgtttat1560 ggtagcaatc tagcagatgctagttctcagatgagtgccctctttggtggtgtcttcttt1620 atcggtattt tcctatccattatctttatggtcggaactgttctggtcatctactacaaa1680 caaatttctg aaggctacgaagaccgtgaacgctttattatcttgcagaaagtcggtttg1740 gaccaaaagc aaatcaagcaaaccatccacaaacaggttttaactgttttcttccttcct1800 ttgctctttg ccttcatacatctcgcctttgcctaccatatgcttagcctgattttaaaa1860 gtgattggtg tactggatacgactatgatgttgattgtgaccttgtctatctgcgctatc1920 3Sttcctcatcg cctatgtgctgattttcatgattacttcaagaagttatcgcaagattgtg1980 caaatgtaa 1989 <210> 79 <211> 891 <212> DNA
<213> Streptococcus pneumoniae <400> 79 atgaaacaag atcaactaaa ggcttggcaa ccagctcagt ttgaccgttt tgtccgtatc 60 45 ttagaacaag accagctcaa tcacgcctat ctcttttcag gtttctttgg aagcttggaa 120 atggcgcaat ttttagctaa gagcctcttt tgtacggata aagttggcgt cttaccatgt 180 gagaaatgcc gaagttgcaa gctgattgaa caggaagagt ttccagatgt caccttgatt 240 aagccagtca atcaggtcat caagacagaa cgcattcggg aattggtggg acagttttct 300 caagcaggga ttgaaagcca gcaacaggtc tttattatcg agcaagcgga taaaatgcat 360 5~ cccaacgcag ccaattctct gctcaaggtc atcgaagaac cccagagtga agtttatatt 420 ttcttcttga ctagcgatga ggaaaagatg ttaccgacaa tccgaagtcg gactcagatc 480 ttccacttta aaaagcaaga agaaaaactt atcttactct tagaacaaat gggacttgtt 540 aagaaaaaag cgactctttt agctaagttt agtcaatcgc gagctgaagc agaaaagttg 600 gctaatcagg caagtttttg gaccttggtc gatgaaagtg aacgcctgct gacttggtta 660 SS gtagctaaga aaaaagaaag ttatctacag gttgccaaat tagccaactt ggcagatgat 720 aaggaaaaac aggatcaggt tttacggatt cttgaagttc tctgtgggca ggacctcttg 780 caggtaagag taagagtgat tctacaagat ttactagaag ctagaaaaat gtggcaagct 840 aatgtcagct ttcaaaatgc catggaatat ctggtcttga aagaaatata a 891 <210> 80 <211> 615 <2l2> DNA
<213> Streptococcus pneumoniae <400> 80 atgaattcat ttaaaaattt cttaaaagag tggggactgt tcctcctaat tctgtcatta 60 l~ ctagctttaa gtcgtatctt tttttggagc aatgttcgcg tagaaggaca ttccatggat 120 ccgaccctag cggatggcga aattctcttc gttgtaaaac accttcctat tgaccgtttt 180 gatatcgtgg tggcccatga ggaagatggc aataaggaca tcgtcaagcg cgtgattgga 240 atgcctggcg acaccattcg ttacgaaaat gataaactct acatcaatga caaagaaacg 300 gacgagcctt atctagcaga ctatatcaaa cgcttcaagg atgacaaact ccaaagcact 360 IS tactcaggca agggctttga aggaaataaa ggaactttct ttagaagtat cgctcaaaaa 420 gcccaagcct tcacagttga tgtcaactac aacaccaact ttagctttac tgttccagaa 480 ggagaatacc ttctcctcgg agatgaccgc ttggtttcga gcgacagccg ccacgtaggt 540 accttcaaag caaaagatat cacaggggaa gctaaattcc gcttctggcc aatcacccgt 600 atcggaaCat tttaa ~ 615 <210> 81 <211> 987 <212> DNA
<213> Streptococcus pneumoniae <400> 81 atggtagtat ttacaggttc aactgttgaa gaagcaatcc agaaaggatt gaaagaatta 60 gatattccaa gaatgaaggc tcatatcaaa gtcatttcta gggagaaaaa aggctttctt 120 ggtctatttg gtaaaaaacc agcccaagtg gatattgaag cgattagtga aacgactgtt 180 gtcaaagcaa atcaacaggt agtaaaaggc gttccgaaaa aaatcaatga.tttgaacgag 240 cctgtgaaga cggttagtga agaaaccgtt. gaccttggtc atgtggttaa tgctattaaa 300 aaaatagagg aagaaggtca aggtatttct gatgaagtca aggctgaaat cttaaaacat 360 gaaagacatg ccagcactat cttagaagaa actggtcaca ttgagatttt aaatgaactt 420 caaatcgagg aagcgatgag ggaagaagca ggcgctgatg accttgaaac tgagcaagat 480 caaactgaaa atcaagactt gaaagagatg ggcttgaagg tcgagcaaag ttatgatatt 540 gcccaggtgg ctacggatgt gactgcctat gttcaagcga ttgtggatga catggatgtt 600 gaagctacac tttcaaatga ttataaccgt cgtagcatca atctacaaat tgacaccaac 660 gaaccaggtc gtattatcgg ctaccatggt aaagtcttga aggccttgca actgttggct 720 caaaattatc tttacaaccg ctattccaaa accttctacg ttacaatcaa tgtcaatgat 7'80 tatgtcgaac accgtgcaga agtcttgcag acctatgcgc aaaaattggc gaatcgtgtt 840 ttggaagaag gtcgcagtca taaaacagat ccaatgtcaa atagcgaacg caagattatc 900 catcgtatta tttcacgtat ggatggcgtg actagttact ctgaaggtga tgagccaaat 960 cgctatgttg ttgtagatac agaataa 987 <210> 82 <211> 1383 <212> DNA
<213> Streptococcus pneumoniae <400> 82 atgtcaaatt,ttgccattat tttagcagcg ggtaaaggga ctcgcatgaa atctgatttg 60 ccaaaagttt tgcacaaggt tgcgggtatt tctatgttgg aacatgtttt ccgtagtgtg 120 ggagctatcc aacctgaaaa gacagtaaca gttgtaggac acaaggcaga attggttgag 180 gaggtcttgg ctggacagac agaatttgtg actcaatctg aacagttggg aactggtcat 240 gcagttatga tgacagaacc tatcttagaa ggtgtgtcag gacacacctt ggtcattgca 300 ggagatactc ctttaatcac tggtgaaagc ttgaaaaact tgattgattt ccatatcaat 360 cataaaaatg tggccactat cttgactgct gaaacggata atccttttgg ctatggacga 420 attgttcgtaatgacaatgctgaggttcttcggtcattgttgagcagaaggatgctacag480 attttgaaaagcaaatcaaggaaatcaacactggtaacatacgtctttgacaacgagcgt540 ttgtttgaggctttgaaaaatatcaataccaataacgctcaaggcgaatactatattaca600 gacgtcattggtattttccgtgaaactggtgaaaaagttggcgcttatactttgaaagat660 tttgatgaaagtcttggggtaaatgaccgtgtggcgcttgcgacagctgagtcagttatg720 cgtcgtcgcatcaatcataaacacatggtcaacggtgttagctttgtcaatccagaagca780 acttatatcgatattgatgttgagattgctccggaagttcaaatcgaagccaatgttatc840 ttgaaagggcaaacgaaaattggtgctgagactgttttgacaaacggtacttatgtagtg900 gacagcactatcggagcaggagcggtcattaccaattctatgattgaggaaagtagtgtt960 1~ gcagacggtgtgacagtcggtccttatgctcacattcgtccaaattcaagtctgggtgcc1020 caagttcatattggtaactttgttgaggtga~aaggatcttcaatcggtgagaataccaag1080 gctggtcatttgacttatatcggaaactgtgaagtgggaagcaacgttaatttcggtgct1140 ggaactattacagtcaactatgacggcaaaaacaaatacaagacagtcattggagtcaat1200 gtctttgttggttcaaattcaaccattattgcaccagtagaacttggtgacaattccctc1260 IS gttggtgctggttcaactattactaaagacgtgccagcagatgctattgctattggtcgc1320 ,ggtcgtcagatcaataaagacgaatatgcaacacgtcttcctcatcatcc.taagaaccag1380 tag 1383 <210> 83 <211> 936 <212> DNA

<213> Streptococcus pneumoniae <400> 83 ZS atgtccaagattctagtatttggtcaccaaaatccagactcagatgccatcggatcatct60 gtagcttttgcctaccttgcaaaagaagcttacggtttggatacggaagctgttgccctt120 ggaactccaaatgaagaaacagcctttgtcttgaactattttggtgtggaagcaccaGgt180 gttatcacttctgccaaagcagagggggcagagcaagttatcttgactgaccacaatgaa240 ttccaacaatctgtatcagatatcgctgaagtagaagtttacggtgttgtagaccaccac300 30 cgtgtggctaactttgaaactgcaagcccactttacatgcgtttggagccagttggatca360 gcgtcttcaatcgtttaccgtatgttcaaagaacatggtgtagctgttcctaaagagatt420 gcaggtttgatgctttcaggtttgatttcagatacccttcttttgaaatcaccaacaaca480 cacccaacagataaaatcattgctcctgaattggctgaattggctggtgtaaacttggaa540 gaatatggtttggcaatgttgaaagctggtaccaacttggctagcaaatctgctgaagaa600 35 ttgattgacatcgatgctaagacttttgaactcaacggaaataatgtccgtgttgcccaa660 gtgaacacagttgacatcgctgaagttttggaacgccaagcagaaattgaagctgcaatg720 caagctgccaacgaatcaaacggctactctgactttgtcttgatgattacagatatcgtc780 aactcaaactcagaaatattggctcttggtgccaatatggacaaggtcgaagcggctttc840 aatttcaaacttgaaaacaatcatgccttccttgctggtgccgtttcacgtaagaaacaa900 gtggtacctcaattaactgaaagctttaatacgtaa 936 <210> 84 <211> 678 <212> DNA

4S <213> Streptococcus pneumoniae <400> 84 atgatttcaa agagattaga attggtagct tcctttgtgt cacagggggc tattttacta 60 gatgtgggaa gtgaccatgc ttatctgcct atcgagttgg ttgagagagg ccaaatcaaa 120 50 agcgctattg caggtgaggt ggtggaaggt ccctatcagt ctgcggttaa aaatgttgag 180 gctcacggcc taaaggagaa aatccaagtc cgtttagcca atggcttggc agcttttgaa 240 gagactgacc aagtgtctgt cattaccatt gctggcatgg gtggtcgttt gattgctagg 300 attttagaag aaggtttggg gaagttagct aatgtagagc gtttgatcct ccagcccaat 360 aatcgtgaag acgacttgcg tatctggcta caggatcatg gattccagat tgtagcagaa 420 SS agcatcttag aagaagctgg aaagttttat gagattttgg tggtggaagc aggacaaatg 480 aagctatcag ccagtgatgt tcgctttggt cccttcttgt ccaaagaagt cagtccagta 540 tttgtccaaa aatggcaaaa agaagctgag aagctagagt tcgccctcgg acaaatccca 600 gaaaaaaatc tggaagaacg tcaagttcta gtagataaga ttcaagctat caaggaggtg 660 ctccatgtta gcaagtga 678 <210> 85 <211> 486 <222> DNA
<213> Streptococcus pneumoniae <400> 85 atgaatttaaacgatattaaagacttgatgactcaatttgaccagtcaagtttgagagaa60 ttttcttataaaaatgggacggatgagttgcagtttagcaagaatgaagcgagacctgtg120 ;3., cctgaagtt caactcaagtcgctccagcag caacaccgagtccagtagct180 cccgttctag cctacatctgctccagcagagactgtagcagaagaagttccagctccagctgaagcaagt240 gtggctagtgagggaaatcttgtagaga.gtccacttgttggagtggtttacttggctgct300 IS ggaccagataaacctgccttcgttacagttggtgatagtgtcaaaaaaggtcaaacattg360 gtaattatcgaagccatgaaagtcatgaatgaaatcccagctcctaaggatggtgtggta420 acggaaattctcgtctctaacgaagaaatggttgagtttggtaaaggattggtacgtatc480 aaatga 486 <210> 86~

<211> 1236 <212> DNA

<213> Streptococcus pneumoniae <400> 86 atgaaactaaatcgagtagtggtaacaggttatggagtaacatctccaatcggaaataca60 ccagaagaattttggaatagtttagcaactgggaaaatcggcattggtggcattacaaaa120 tttgatcatagtgactttgatgtgcataatgcggcagaaatccaagattttccgttcgat180 aaatactttgtaaaaaaagataccaaccgttttgataactattctttatatgccttgtat240 gcagcccaagaggctgtaaatcatgccaatcttgatgtagaggctcttaatagggatcgt300 tttggtgttatcgttgcatctggtattggtggaatcaaggaaattgaagatcaggtactt360 cgccttcatgaaaaaggacccaaacgtgtcaaaccaatgactcttccaaaagctttacca420 aatatggcttctgggaatgtagccatgcgttttggtgcaaacggtgtttgtaaatctatc480 aatactgcctgctcttcatcaaatgatgcgattggggatgccttccgctc~cattaagttt540 3S ggtttccaagatgtgatgttggtgggaggaacagaagcttctatcacaccttttgccatc600 gctggtttccaagccttaacagctctctctactacagaggatccaactcgtgcttcgatc660 ccatttgataaggatcgcaatgggtttgttatgggtgaaggttcagggatgttggttcta720 gaaagtcttgaacacgctgaaaaacgtggagctactatcctggctgaagtggttggttac780 ggaaatacttgtgatgcctaccacatgacttctccacatccagaaggtcagggagctatc840 waaggccatcaaactagccttggaagaagctgagatttctccagagcaagtagcctatgtc900 aatgctcacggaacgtcaactcctgccaatgaaaaaggagaaagtggtgctatcgtagct960 gttcttggtaaggaagtacctgtatcatcaaccaagtcttttacaggacatttgctgggg1020 gctgcgggtgcagtagaagctatcgtcaccatcgaagctatgcgtcataactttgtacca1080 atgacagctgggacaagtgaagtatcagattatatcgaagctaatgtcgtttatggacaa1140 4S ggcttggagaaagaaattccatacgctatttcaaatacttttggttttggaggccacaat1200 gcagttcttgctttcaaacgttgggagaatagataa 1236 <210> 87 <211> 1080 SO <212> DNA

<213> Streptococcus pneumoniae <400> 87 atgaacatctatgatcaactacaagttgtagaagaccgttatgaagaattaggagaattg60 SS ctgagtgaccctgatgtcgtttcagacaccaagcgttttatggagctttcaaaagaagaa120 gcttccaatcgtgacaccgtaatagcctaccgtgagtataaacaagtccttcaaaatatc180 gtcgatgccgaagagatgattaaggaatcaggcggagatgcggacttggaagaattggcc240 aagcaagaac tcaaagatgc caaggctgaa aaagaagaat atgaagaaaa actgaaaatt 300 ttgctccttc caaaggatcc aaacgatgac aagaatatca tccttgaaat ccgtggagca 360 gctggtggag acgaagcggc acttttcgct ggagatttgc taactatgta ccaaaagtat 420 gcggaagccc aaggttggcg ctttgaagtc atggaagcct ctatgaatgg tgtcggtggt 480 tttaaagaag tggttgctat ggtttcaggt cagtctgtat actctaagct taagtatgaa 540 tcaggtgccc accgtgtgca acgtgttcct gtgacagaaa gccaaggccg tgttcatact 600 tcgacagcga cagttcttgt tatgccagaa gttgaagagg ttgaatacga cattgatcca 660 aaagaccttc gtgtcgacat ctatcacgcc tctggtgctg gtggacagaa cgtcaataag 720 gttgcgactg ccgttcgtat cgttcacttg ccaaccaata tcaaggttga gatgcaggaa 780 gaacgtaccc agcagaagaa ccgcgagaag gctatgaaga ttatccgtgc acgcgtcgct 840 gaccactttg ctcagattgc tcaggatgaa caagacgctg agcgtaagtc gacaatcggt 900 actggtgacc gttcagaacg gatccgaact tataacttcc cacaaaaccg tgtcacagac 960 caccgtatcg gcttgaccct ccaaaaacta gatacgattt tgtctggtaa attggacgaa 1020 gttgtggatg ccttggtgct ttatgaccaa acacaaaaac tagaagaatt aaacaaataa 1080 <210> 88 <211> 1680 <212> DNA
<213> Streptococcus pneumoniae <400> 88 atggcctacactcttaaacctgaagaagttggtgtttttgccatcggtggtctaggagaa60 atcgggaaaaacacttacggaattgaataccaagacgagattatcatcgtcgatgctggg120 attaaattcccagaagatgacttgcttggtatcgactatgtcattcctgactactcttac180 2S atcgtagacaatatcgaccgcgtcaaggctgttttaatcacacacggacacgaggaccac240 attggtgggattccgttcctactcaagcaagcaaatgtccctatttatgctggaccgctt300 gccttggctttgatccgtgggaaactcgaagaacacggcctcttgcgcaacgccaaactt360 tacgaaatcaaccacaacaccgagttgacctttaaaaatctcaaggcaacttt.ctttaga420 acgactcactctattccagagcctttggggattgtcattcatactcctcaagggaaaatc480 3~ gtctgtacgggtgactttaagttcgactttactccagttggagaacctgcggacttgcat540 cgtatggctgcgcttggtgaagaaggcgtgctctgtctcctgtctgactcgacaaatgcg600 gaagtaccaacctttaccaactctgaaaaagtcgttggtcagtccattatgaagattatc660 caaggtattgaaggacgtatcatctttgcatcctttgcctcaaatatcttccgtctccag720 caggcaacagaagctgctgttaagactggacgcaagattgcggtctttggtcgttctatg780 35 gaaaaggccattgtcaacggaatcgatcttggctacatcaaagctcctaagggaaccttt840 atcgagccaaatgaaatcaaagattatcctgcaggagaagttcttatcctctgtacaggt900 agtcagggtgagcctatggcagccctctctcgtatcgccaacggaacccaccgtcaagta960 caattacaaccaggtgataccgttatcttctcttctagtcccatccctggaaacactact1020 agcgtcaacaagctgattaacatcatttctgaagctggtgtcgaagttatccacggtaaa1080 4o gtgaacaatatccatacatctggacacggtggtcagcaagagcaaaaactcatgctctgc1140 ttgattaagccaaaatacttcatgcctgtccacggtgaataccgcatgcaaaaagtccac1200 gctggactagcagtggatactggtgttgagaaggacaatatctttatcatgagcaatggc1260 gatgtgcttgcccttactgctgactcagctcgtatcgcaggtcatttcaacgcccaagat1320 atctatgtcgatggaaatcgtatcggtgaaattggcgcagctgtcctcaaagatcgtcgc1380 45 gatctatctgaagacggtgtcgttctggcagtcgcaactgttgacttcaaatcgcagatg1440 attctgtctggcccagatatcctcagccgaggctttgtctacatgagagagtctggagac1500 ttgattcgccaaagccagcgtatcctcttcaatgccattcgtatcgcactgaaaaataag1560 gatgctagcgtgcaatctgtcaatggtgccattgtcaacgctattcgccccttcctctat1.620 gaaaataccgaacgtgaaccgatcatcatcccgatgatcctcacaccagatgaagaataa1680 5~

<210> 89 <211> 1362 <212>~ DNA
<213> Streptococcus pneumoniae <400> 89 atggcagaag tagaagagtt acgagtacaa cctcaagata tcttagctga gcaatccgtt 60 ttaggggcta tctttattgatgagagtaaacttgtttttgtgcgagaatacattgagtct120 cgggactttt ttaagtatgcccatcgtttgattttccaagccatggtcgatttatccgat180 cgtggtgatg ccatagatgcaacaacggttcgtactatccttgataatcaaggtgattta240 cagaatattg gtggcttgtcttacttggttgagattgttaattctgtgccaacttctgct300 aatgcggagt attatgctaagattgttgcagaaaaagcaatgctacgtcgtttaattgcc360 aagttgacag agtctgtcaaccaagcttacgaagcgtcacaaccagctgatgaaattatt420 gctcaggcag aaaaagggttgattgatgtcagtgaaaatgcaaatcgaagcgggtttaag480 aacattcgag atgtgttgaatctcaactttggaaatctggaagctcgctcgcaacaaacg540 accgatatta caggtattgcgacaggttatcgtgatttggatcatatgacaacaggactt600 1~catgaggagg agttgattatcttagcagctcgtccagcagttggtaagacagcatttgcc660 ttgaatatcg ctcagaacattgggactaagttggacaaaacggttgctattttttcactc720 gaaatgggtg cggaaagcttggtagatcgtatgttagctgcagaaggcttggtggagtca780 cattctatcc gtacagggcaattgacagatgaggagtggcaaaaatatactattgctcag840 ggtaatctag ctaacgccagtatctatatcgatgatacgccaggtattcggattacagag.900 ISattcgttctc gttctcgtaaattggctcaagaaactggaaatcttggtttgattgtgata960 gactatttgc aacttatcacgggaactggtcgagaaaatcgtcaacaagaagtttctgaa1020 atttctcgtc agttgaaaatactagccaaggaattgaaggttccagtaatcgctctgagt1080 cagctttctc gtggtgtagaacaacgtcaggacaagagaccggtcttgtctgatattcgt1140 gaatctgggt ctattgagcaggacgctgatatcgtagcttttctctatcgcgatgactac1200 2~tatgaacgtg gtggtgaagaagaggagggtatcccaaataataaggtggaagttattatc1260 gagaaaaacc gtagtggagctcgtggaacagtggaattgattgtccaaaaagaatacaat1320 aaattcttca agtattcaagtatctcaaagagggaggcatas _ 1362 <210> 90 2S<211> 693 <212> DNA

<213> Streptococcus pneumoniae <400> 90 3~atggcgtata aatatttagtgattgtagaatcacctgcaaaagccaagacaattgagaaa60 tatcttggac gaaactataaagtaatggccagtgttggccatataagagatttaccgaaa120 agtaaaatgg gtatcgattttgaaaacaattatgaaccccattatatttctatacgcgga180 aaaggcgatg tcatcaaaagcctgaaagccgcagcaaaaaaagctcaaaaagtttacttg24'0 gcaagtgacc cggatagagaaggagaagcgattgcttggcatttagcgtacctacttggg300 35ttggatctga aagaaaaaaatcgggtggtcttcaatgaaatcacaaaagacgcagtcaaa360 gcagctttta aggaaccaagaacgatcgatgtagatttagtagat,gcacagcaagctcgt420 cgtaccttag acagaatcgttggttattcgatcagtcctattctctggcgtaaggtcaag480 aaagggttaa gtgcaggacgtgtccaatctgtcgctttaaaaattattattgaccgtgaa540 aaagagatcc gagaatttgttccagaagaatattggagcatcgacggtaattttaaaaaa600 4~gctcgcaaga aattcaaagcaaatttctggggaatcgacggtaagaaaaagaaattacca660 gatgcacaaa gtgtaaaaagaagtcactgctag 693 <210> 91 <211> 981 45<212> DNA

<213> Streptococcus pneumoniae <400> 91 atgtttattt ccatcagtgctggaattgtgacatttttactaactttagtaggaattccg60 50gcctttatcc aattttatagaaaggcgcaaattacaggccagcagatgcatgaggatgtc120 aaacagcatc aggcaaaagctgggactcctacaatgggaggtttggttttcttgattact180 tctgttttgg ttgctttctttttcgccctatttagtagccaattcagtaataatgtggga240 atgattttgt tcatcttggtcttgtatggcttggtcggatttttagatgactttctcaag300 gtctttcgta aaatcaatgaggggcttaatcctaagcaaaaattagctcttcagcttcta360 SSggtggagtta tcttctatcttttctatgagcgcggtggcgatatgctttctgtctttggt420 tatcaagtgc atctagggattttctatattgttttcgctcttttctggctagtcggtttt480 tcaaacgcag taaacttgacagacggtgttgacggtttagctagtatttccgttgtgatt540 3~ gtctgtacgggtgactttaagttcgactttactccagttggagaacctgcggacttgcat540 cgtatggctgcgcttggtgaagaaggcgtgctctgtctcctgtctgactcgacaaatgcg600 gaagtaccaacctttaccaactctga agtttgtctg cctatggagt tattgcctat gtgcaaggtc agatggatat tcttctagtg 600 attctggcca tgattggtgg tttgctcagt ttcttcatct ttaaccataa gcctgctaag 660 atctttatgg gtgatgtggg aagtttggct ttaggtggaa tgctggcagc tatctctatg 720 gctctccacc aagaatggac tctcttgatt atcggaattg tgtatgtttt tgaaacaact 780 tctgttatga tgcaagtcag ttatttcaaa ctgacaggtg gtaaacgtat tttccgtatg 840 acgcctgtac atcaccattt tgagcttggg ggattgtctg gtaaaggaaa tccttggagc 900 gagtggaagg ttgacttctt cttttgggga gttgggcttc tagcaagtct cctgacccta 960 gcaattttat atttgatgta a 981 1~ <210> 92 <211> 2082 <212> DNA
<213> Streptococcus pneumoniae IS <400> 92 atggcacgcgaattttcacttgaaaaaactcgtaatatcggtatcatggctcacgtcgat60 gccggtaaaacaacaactactgagcgtattctttactacactggtaaaatccacaaaatc120 ggtgaaactcacgaaggtgcgtcacaaatggactggatggagcaagagcaagaacgtggt180 atcacgatcacatctgctgcgacgacagctcaatggaacaaccaccgcgtaaacatcatc240 gacacaccaggacacgtggacttcacaatcgaagtacaacgttctcttcgtgtattggat300 ggtgcggttaccgttcttgactcacaatcaggtgttgagcctcaaactgaaacagtttgg360 cgtcaagcaactgagtacggagttccacgtatcgtatttgccaacaaaatggacaaaatc420 ggtgctgaettcctttactctgtaagcacacttcacgatcgtcttcaagcaaatgcacac480 ccaatccaattgccaatcggttctgaagatgacttccgtggtatcattgacttgatcaag540 ~S atgaaagctgaaatctatactaacgaccttggtacggatatccttgaagaagacatccca600 gctgaataccttgaccaagctcaagaataccgtgaaaaattgattgaagcagttgctgaa660 actgacgaagaattgatgatgaaatacctcgaaggtgaagaaatcactaacgaagaattg720 aaagctggtatccgtaaagcgactatcaacgttgaattcttcccagtattgtgtggttca780 gccttcaaaaacaaaggtgttcaattgatgcttgatgcggttatcgactaccttccaagc840 3o ccacttgacatcceagcaatcaaaggtattaacccagatacagacgctgaagaaattcgt900 ccagcatctgacgaagagccatttgcagctctt gccttcaagatcatgactgacccattc960 gtaggtcgtttgacattcttccgtgtttactcaggtgttcttcaatcaggttcatacgta1020 ttgaatacttctaaaggtaaacgtgaacgtatcggacgtatccttcaaatgcacgctaac1080 agccgtcaagaaatcgacactgtttactcaggtgatatcgctgctgccgttggtttgaaa1140 35 gatactacaactggtgactcattgacagatgaaaaagctaaaatcatccttgagtcaatc1200 aacgttccagaaccagttatccaattgatggttgagccaaaatctaaagctgaccaagac1260 aagatgggtatcgcccttcaaaaattggctgaagaagatccaacattccgcgttgaaaca1320 aacgttgaaactggtgaaacagttatctcaggtatgggtgaacttcaccttgacgtcctt1380 gttgatcgtatgcgtcgtgagttcaaagttgaagcgaacgtaggtgctcctcaagtatct1440 taccgtgaaacattccgcgcttctactcaagcacgtggattcttcaaacgtcagtctggt1500 ggtaaaggtcaattcggtgatgtatggattgaatttactccaaacgaagaaggtaaagga1560 ttcgaattcgaaaacgcaatcgtcggtggtgtggttcctcgtgaatttatcccagcggtt1620 gaaaaaggtttggtagaatctatggctaacggtgttcttgcaggttacccaatggttgac1680 gttaaagctaagctttatgatggttcatatcacgatgtcgactcatctgaaactgccttc1740 45 aagattgcggcttcactttcccttaaagaagctgctaaatcagcacaaccagctatcctt1800 gaaccaatgatgcttgtaacaatcactgttccagaagaaaaccttggtgatgttatgggt1860 cacgtaactgctcgtcgtggacgtgtagatggtatggaagcacacggtaacagccaaatc1920 gttcgtgcttacgttccacttgctgaaatgttcggttacgcaacagttcttcgttctgca1980 tctcaaggacgtggtacattcatgatggtatttgaccactacgaagatgtacctaagtca2040 SD gtacaagaagaaattattaagaaaaataaaggtgaagactas 2082 <210> 93 <211> 1227 <212> DNA

SS <213> Streptococcus pneumoniae <400> 93 atgccaaattacaa~attccattttcaccgcctgatatcacagaagcagaaattgctgaa60 gtagcggataccctgcgttctggttggatcacaacaggtcctaaaacaaaagaactggag120 cgccgcttgtctctttacacacagacacctaagactgtttgtctcaactctgcgacagcc180 gctctggagttgattttacgcgttttggaagtgggacctggtgatgaagtcatcgttcca240 S gccatgacctatacggcttcatgtagtgtcattacgcacgtgggagcaacccctgtcatg300 gtggatatccaagcagatacgtttgagatggactatgacctgcttgagcaagctatcact360 gagaaaactaaggtgattatcccagtagagctcgcagggattgtttgcgattatgaccgt420 ttgttccaagtcgtggagaaaaaaegtgacttctttaccgcttcaagcaagtggcaaaag480 gcctttaaccgtattgtcattgtctctgatagtgcccacgctttgggatctacttataaa540 1~ ggacaaccttctggttctatcgctgattttacttccttctcattccatgccgttaagaac600 tttacaacggcagaaggtggaagtgcgacttggaaagccaatccagtgattgatgacgaa660 gagatgtacaaggaattccaaatcctttcccttcacgggcaaactaaggatgctcttgcc720 aagatgcaactggggtcatgggaatacgatatcgttacaccagcctataagtgcaacatg780 accgatatcatggcttcacttggtttggtacaattggaccgctatccaagtttgttgcaa840 IS cgccgtaaggacattgtggaccgctatgatagtggttttgcaggttctcgcatccatcct900 ttggcacacaagactgaaactgtcgaatcttcacgccacctctacatcacccgtgtagaa960 ggagcaagcctagaagaacgcagcctcatcatccaagaattggctaaagcaggaattgca1020 agtaatgttcactacaaaccgcttcctctcttgacagcctataagaatcttggatttgat1080 atgacgaactatcctaaggcctatgccttctttgagaatgaaattaccctccctcttcat1140 20 actaaattaagcgatgaagaagtagactatatcattgagactttcaaaacagtttctgaa1200 aaagtgctaactttatcaaaaaaatga 1227 <210> 94 <211> 978 25 <212> DNA

<213> Streptococcus pneumoniae <400> 94 atgacagaacctgatttttggaacgataatattgcggcccaaaaaacgtcgcaagaattg60 aatgtatttaaaaacacttacaataccttccataagatggaagagttgcaggatgaagtc120 gaaattttattggattttttggctgaagacgagtcagtgcatgatgaactggtagcgcag180 ttagccgaacttgataagataatgaccagctacgagatgactttactcttgtcagaacct240 tatgaccacaacaatgccatcttggaaatccatccaggttctggtggtactgaggcgcag300 gactggggtgatatgttgcttcgtatgtatactcgttatggtaatgctaaaggctttaaa360 35 gtggaagtgttggattaccaagcaggtgatgaggctggtattaagtcggtaactttatca420 tttgaagggcctaatgcctatggtctcctcaagtcagaaatgggtgttcaccgcttagtg480 cgaatctcaccatttgactctgccaaacgtcgccatacctctttcacatctgtagaagtg540 atgccagaattggatgatactattgaagtggaaatccgtgaagatgatatcaagatggat600 ac.cttccgttcaggtggtgccggtggacaaaacgtcaataaagttteaacaggtgtacgt660 40 ttaacccacattccaactgg.aattgttgtccaatcaacagtggatcgtacccagtatgga720 aatagagatcgtgccatgaagatgttgcaggctaagctctatcaaatggagcaagagaag780 aaggctgcggaggtagattctctcaaaggtgagaaaaaggagattacttggggaagccaa840 atccgttcttatgtcttcacgccttatactatggtaaaagatcaccgaactagctttgag900 gttgctcaggtagataaggttatggatggggacctagatggttttatcgatgcttatctc960 4S aagtggcgaattagctaa g7g <210> 95 <211> 750 <222> DNA

SO <213> Streptococcus pneumoniae <400> 95 atgttttatacttatttgcgtggattagttgtattgctcttatggtccatcaatggcaat60 gctcactatcataatactgataaaattcctaatcaagatgaaaattatattttagttgcg120 SS cctcaccgtacctggtgggatcctgtttatatggcctttgcgaccaagccaaaacagttc180 atctttatggcaaaaaaagaactctttaccaaccgtatctttggttggtggattcgtatg240 tgtggcgcctttcccatcgaccgtgaaaatcccagcgcctcagccatcaaatatcctatc300 aacgttctca aaaaaagtga ccgctctctc atcatgtttc caagtggtag ccgccactca 360 aacgatgtca aggggggcgc agcactgatt gccaaaatgg ccaaggtccg tatcatgccg 420 gttacctaca ccggtcccat gactttgaag ggcttgatta gccgtgaacg tgtcgatatg 480 aactttggaa atccaatcga tatctcagat atcaagaaaa tgaatgatga aggcattgaa 540 acagtcgcca atcgtattca aacagaattc caacgtctgg acgaagaaac gaaacaatgg 600 cacaatgata aaaaaccaaa tccactctgg tggtttatcc gcatccctgc cctcatcctt 660 gctattatcc tcgctatcct aaccatcatc tttagcttta tcgcaagctt catctggaac 720 ccagataaga aaagagaaga acttgcatag 750 <210> 96 <211> 3102 <212> DNA
<213> Streptococcus pneumoniae IS <400> 96 ttgatcgcacaactagatacaaaaacagtctatagttttatggaaagcgtcatttcgatc60 gaaaagtatgtgagagcagctaaagaatacggctacactcatttggctatgatggatatt120 gacaatctttatggcgctttcgactttctagagattacaaaaaaatacggcattcatcct180 ttgctagggcttgaaatgacagtgtttgtagatgatcagggagtaaatttgcgcttttta240 gctctatctagtgtgggctatcagcagttgatgaagctttcgacagccaagatgcagggg300 gagaaaacttggtcagtcctgtcccagtacctggaggatatcgcggtcattgtgccttat360 tttgatagagttgagtcgttagaactaggctgtgattactatataggggtttatccagaa420 acactagcaagcgaatttcatcatcctatcttacctctttatcgggtcaacgcttttgaa480 agcagggatagagaagtt~cttcaagttttaacagcgattaaagaaaatctaccgctcaga540 ~S gaagttcccttgcgttcgagacaagatgtctttatatcagcaagttctttagagaaacta600 ttccaagagcgttttccgcaagctttggacaatttagaaaagcttatttcaggcat 660 tct tacgacttggatactagtctgaaactgcctcgttttaatccagctagaccagcagtagag720 gagttgagagagcgtgctgaactggggcttgttcagaaggggttgactagtaaagaatat780 caagatagactagaccaagaattgtctgttattcatgatatgggctttgatgattatttc840 ttggttgtttgggatttgttgcgttttggacgatcgaatggctattatatgggaatggga900 aggggttctgcagtaggcagtttggtttcttatgccttagacatcacggggattgaccca960 gtagagaaaaatctgatttttgaacgctttcttaatcgtgaacgctataccatgcctgat1020 attgatattgatatcccagatatttatcgtccagattttatcagatatgttggtaataaa1080 tatggtagtaaacatgcggcacaaatcgttactttttcaacctttggagccaagcaagct1140 cttcgagatgtcttgaaacgctttggtgtgccagagtatgaattatctgcaattactaag1200 aaaatcagttttcgtgacaatcttaagtcggcctatgagggcaatctccagtttcgtcag1260 caaatcaatagtaagttagaataccaaaaagcttttgagattgcttgcaagatagagggc1320 tatccaa,ggcaaacctctgtccatgcggctggtgttgtaattagtgaccaagatttaacc1380 aactacattcctctaaagtatggtgatgaaattccactgactcagtatgatgctcatgga1440 gttgaggctagcggacttttgaagatggactttctgggactacgaaatttgacctttgtc1500 cagaagatgcaagagttgcttgctgaaatagaaggtattcaccttaaaattgaagaaata1560 gatttggaagacaaagaaacgttagatttatttgcctctggaaatacaaaaggtatcttt1620 caatttgagcaacctggtgc.tattcgcttgctcaaacgtgttcaaccagtctgtt 1680 ttgaa gatgtcgtagcaactacttctctaaatcgaccgggtgctagtgactatatcaataatttt1740 gtggcaagaaagcatgggcaggaagaagtgactgttctggatccagtactggaggatatt1800 ttggctccaacctacggcataatgctctatcaggagcaggttatgcaggttgcccagcga1860 tttgccggatttagtcttgggaaagccgatattttgcgtcgggctatggggaaaaaggat1920 gcctctgccatgcatgagatgagggcttcctttattcaaggttcattagaagctggtcat1980 actgtggaaaaagcagagcaggtctttgatgttatggagaagtttgcaggctatggtttt2040 aacaggtcacacgcctatgcctactcagcattggccttccagttggcttattttaaaaca2100 cattatccagccatattttatcagatcatgttgaattctgccaacagtgattacttaata2160 gatgcacttgaagcaggttttgaagtggcgcctctgtccatcaacacgattccctatcac2220 gataaaattgccaacaaggccatctatctaggtttgaaatccattaaaggagtcagtaat2280 gatttagctctctggattattgaacatagaccttattctaatattgaagattttatagct2340.

SS aaattacctgagaattatctgaaacttcctctgctagaacctttggtaaaagttggtctt2400 ttcgattcatttgaaaaaaatcgtcaaaaagtatttaataacttagctaatctatttgaa2460 tttgtgaaagagttgggaagtttgtttggagatgctatttatagttggcaggaatcggaa2520 gattggacggaacaagaaaaattttatatggaacaagagcttttagggataggtgtcagc2580 aaacatccactacaagctattgcaagtaaggctatttacccgattaccccaatcggaaat2640 ttgtcagaaaatagctatgctattattttggttgaagttcagaaaataaaagtgattcgt2700 accaaaaagggtgaaaatatggccttcttacaggcagatgatagtaagaaaaaattggat2760 $ gtcactctcttttcagacttatatcgtcaggttggacaggaaataaaagagggagccttc2820 tactatgtaaaaggaaaaatacaatcacgtgatggccgtctgcaaatgattgcacaagaa2880 ataagagaagcagttgctgaacgcttttggatacaggtgaaaaatcatgaatcggatcaa2940 gaaatttcacgtattttagaacaatttaaaggcccaatcccagtcatcatccggtatgaa3000 gaggaacagaaaaccatcgtttctccccatcattttgtagctaaatccaatgaattagag3060 l~ gagaaattgaatgaaatcgttatgaaaacgatttatcgctas 3102 <210> 97 <211> 921 <212> DNA

IS <213> Streptococcus pneumoniae <400> 97 atgaccaacgaatttttacattttgaaaaaatcagccgccagacttggcaatctttacat60 cgaaagacaacacctcctttgacagaagaagaattggaatctatcaagagttttaatgac120 caaatcagtctccaagacgttacagatatctatctccccttggctcatctgattcagatt180 tacaagcgaactaaggaagatttagccttttcaaaaggaattttcctccaacgtgaaagt240 aaatctcaaccttttattattggggtttctgggagtgttgccgttggaaaatccacaacc300 agtcgcctacttcaaatcctactgtcccgtacgtttacagatgctacggttgagttggtt360 acaactgatggttttctctatcccaatcaaaccttgattgagcagggaattttaaatcgt420 ~5 aaaggatttcctgaaagctatgatatggaagctcttctcaacttcttggaccgcatcaaa480 aatggacaagatgtagatattcctgtctattctcatgaagtttacgacatgtacccaaa 540 c aagaaacaaagtgtcaaagctgctgattttgtaatcgttgagggaattaatgtctttcaa600 aatccacaaaacgatcgtctctatatcactgacttctttgacttttccatctatgtagat660 gctggagtggatgatattgaaagttggtatctggaccgtttcttgaaaatgctgagtcta720 3~ gcccaaaacgaccctgatagctactattatcgttttactcagatgccgattggggaagtg780 gagtcctttgcccatcaggtctggaccagtatcaatctcacaaatctgcaaaattatatt840 gaaccaaccagaaatcgtgcagaagtgattcttcataaaagcaagaaccatgaaatcgat900 gaaatttacttaaaaaagtaa 921 35 <210> 98 <211> 741 <212> DNA

<213> Streptococcus ' pneumoniae 40 <400> 98 atggaaatttcattattaacagatgttggtcagaaacgaacaaataaccaagactatgtc60 aaccactatgtcaatagagctggacgtaccatgattattttagctgatgggatgggaggt120 catcgtgcagggaatatcgctagtgaaatggcggtcacagacctgggtgtagcttgggtt180 gatacccagatcgatacagtcaatgaagtgcgtgaatggttcgcccattacctagaaatt240 _ 4$ gaaaatcaaaagattcaccagcttggtcaggatgaagcttacagaggcatgggaactact300 ttggaagtccttgctattattgataatcaggctatctatgctcatattggtgattcgcgt360 atcggcttgattcgtggagaagaataccatcagttgacgagcgatcattccttggttaat~420 gaattgctcaaggctggtcaattgacaccagaagaggcagaagctcatccgcaaaaaaat480 attatcacccagtctattgggcaaaaagatgaaattcagcctgattttgggacagttatc540 50 cttgagtcaggtgactatctcttgctcaatagtgacggcttgaccaacatgatttcaggc600 agtgagattcgtgatattgtaaccagtgatattcctttagcagataaaacggagacactt660 gttcgttttgctaacaatgcaggaggtttagacaacattacggttgcccttgtttctatg720 aacgaggaggatgaagaatga 741 $5 <210> 99 <211> 831 <212> DNA

<213> Streptococcus pneumoniae <400> 99 gtgacgatac agatgaagaa tacaggtaaa cgaattgatc tgatagccaa tagaaaaccg 60 cagagtcaaa gggtcttgta tgaattgcga gatcgtttga agagaaatca gtttatactc 120 aatgatacca atccggatat tgtcatttcc attggcgggg atggtatgct cttgtcggcc 180 tttcataagt acgaaaatca gcttgacaag gtccgcttta tcggtcttca tactggacat 240 ttgggcttct atacagatta tcgtgatttt gagttggaca agctagtgac taatttgcag 300 ctagatactg gggcaagggt ttcttaccct gttctgaatg tgaaggtctt tcttgaaaat 360 l~ ggtgaagtta agattttcag agcactcaac gaagccagca tccgcaggtc tgatcgaacc 420 atggtggcag a.tattgtaat aaatggtgtt ccctttgaac gttttcgtgg agacgggcta 480 acagtttcga caccgactgg tagtactgcc tataacaagt ctcttggcgg tgctgtttta 540 caccctacca ttgaagcttt gcaattaacg gaaattgcca gccttaataa tcgtgtctat 600 cgaacactgg gctcttccat tattgtgcct aagaaggata agattgaact tattccaaca 660 agaaacgatt atcatactat ttcggttgac aatagcgttt attctttccg taatattgag 720 cgtattgagt atcaaatcga ccatcataag attcactttg tcgcgactcc tagccatacc 780 agtttctgga accgtgttaa ggatgccttt atcggtgagg tggatgaatg a 831 <210> 100 2~ <211> 1623 <212> DNA
<213> Streptococcus pneumoniae <400> 100 atgtcaaaagaaattaaattttcatcagatgcccgttcagccatggttcgtggtgtcgat60 attcttgcagacactgttaaagtaaccttgggaccaaaaggtcgcaatgtcgttcttgaa120 aagtcattcggttcacccttgattaccaatgacggtgtgaccattgccaaagaaatcgaa180 ttggaagaccattttgaaaatatgggtgctaagttagtatcagaagtagcttctaaaacc240 aatgatatcgcaggtgacggaactacgactgcaacagtcttgacccaagctatcgtccgt300 30 gaaggaatcaaaaacgtcacagcaggtgcaaatccaatcggtattcgtcgtgggattgaa360 acagcagttgccgcagcagttgaagctttgaaaaacaacgccatccctgttgccaataaa420 gaagctatcgctcaagttgcagcagtatcttctcgttctgaaaaagttggtgagtacatc480 tctgaagcaatggaaaaagttggcaaagacggtgtcatcaccatcgaagagtcacgtggt540 atggaaacagagcttgaagtcgtagaaggaatgcagtttgaccgtggttacctttcacag600 35 tacatggtgacagatagcgaaaaaatggtggctgaccttgaaaatccgtacattttgatt660 acagacaagaaaatttccaacatccaagaaatcttgccacttttggaaagcattctccaa720 agcaatcgtccactettgattattgcggatgatgtggatggtgaggctcttccaactctt780 gttttgaacaagattcgtggaaccttcaacgtagtagcagtcaaggcacctggttttggt840 gaccgtcgcaaagccatgcttgaagatatcgccatcttaacaggcggaacagttatcaca900 4~ gaagaccttggtcttgagttgaaagatgcgacaattgaagctcttggtcaagcagcgaga960 gtgaccgtggacaaagatagcacggttattgtagaaggtgcaggaaatcctgaagcgatt1020 tctcaccgtgttgcggttatcaagtctcaaatcgaaactacaacttctgaatttgaccgt1080 gaaaaattgcaagaacgcttggccaaattgtcaggtggtgtagcggttattaaggtcgga1140 gccgcaactgaaactgagttgaaagaaatgaaactccgcattgaagatgccctcaacgct1200 4S actcgtgcagctgttgaagaaggtattgttgcaggtggtggaacagctcttgccaatgtg1260 attccagctgttgctaccttggaattgacaggagatgaagcaacaggacgtaatattgtt1320 ctccgtgctttggaagaacccgttcgtcaaattgctcacaatgcaggatttgaaggatct1380 atcgttatcgatcgtttgaaaaatgctgagcttggtataggattcaacgcagcaactggc1440 gagtgggttaacatgattgatcaaggtatcattgatccagttaaagtgagtcgttcagcc1500 5~ ctacaaaatgcagcatctgtagccagcttgattttgacaacagaagcagtcgtagccaat1560 aaaccagaaccagtagccccagctccagcaatggatccaagtatgatgggcgggatgatg1620 taa 1623 <210> 101 SS <211> 1446 <212> DNA
<213> Streptococcus pneumoniae 41 .

<400> 101 atgattaagattgaaaccgtattagatattttaaagaaagatggcctttttcgcgaaatt60 attgaccaaggtcattaccactacaaetacagcaaagttatttttgatagcatcagctac120 gacagccgaaaagtaacagaagacactcttttttttgcaaaaggcgctgcctttaaaaaa180 gaataccttctttctgctataacacaaggtttagcttggtatgtagctgaaaaggactac240 gaagtcgatatccctgtcatcattgtgaacgatataaagaaagccatgagtttgattgcc300 atggagttctatggtaatccacaagagaaactcaaactccttgcctttactggtactaag360 ggtaagacaacagcaacctatttcgcctataacatcttatctcaggggcatagacctgct420 atgttgtCgaccatgaacacaactcttgatggcgagactttctttaagtcagcgttgaca480 acccctgagagtattgacctctttgacatgatgaatcaggctgtgctaaatgaccgtacc540 cacctcatcatggaagtctccagtcaagcctatctagtccatcgagtctatggactgacc600 tttgatgtaggagtctttcttaacatcactcctgaccatatcggcccgattgaacaccct660 agctttgaagactatttctaccacaagcgtctcttgatggaaaatagccgagcagtcatc720 attaacagtgacatggaccacttctcagtcttgaaagaacaggttgaagatcaagaccat780 gatttctatggtagccaatttgataaccaaatcgagaattccaaagcctttagcttttca840 gctacgggtaaactcgctggagattatgatatccaactcattggcaacttcaaccaagaa900 aatgcagttgctgctggacttgcttgtctccgtctcggagcaagtcttgaggacatcaaa960 aaaggcatcgctgcaacccgcgttcctggtcgtatggaagtcctcactcagaaaaatgga1020 gccaaggtcttcatcgactatgcccacaatggggatagtctgaaaaaactcatcaatgtg1080 gttgaaaCtcatcaaaccggaaagattgctctggttctgggatcaacaggaaacaaggga1140 gaaagtcgtcgtaaggactttggcctcctcctcaatcaacaccctgagattcaagtcttt1200 ctgactgctgatgaccctaactatgaagacccaatggccattgcagatgaaattagtagc1260 tacatcaatcatcctgttgaaaagattgcggatcgccaagaagccatcaaggcggcaatg1320 gctatcacaaatcacgaattagatgcagttattattgcgggtaagggagccgattgttac1380 caaatcatccagggcaagaaagaatcctacccaggagatacagccgtcgcagaaaattat1440 ttataa 1446 <210> 102 <211> 1980 <212> DNA
<213> Streptococcus pneumoniae <400> 102 atgatccaaatcggcaagatttttgccggacgctatcggattgtcaaacagattggtcga60 ggaggtatggcggatgtctacctagccaaagacttaatcttagatggggaagaagtggca120 gtgaaggttctgaggaccaactaccagacggacccgatagctgtagctcgttttcagcgt180 gaagcgagagctatggcagatctagaccatcctcatatcgttcggataacagatattggc240 gaggaagacggtcaacagtacctagctatggagtatgtggctggactggacctcaaacgc300 tatatcaaggaacattatcctctttctaatgaagaagcagtccgtatcatgggacaaatt360 ctcttggctatgcgcttggcccatactcgaggaattgttcacagggacttgaaacctcaa420 aatatcctcttgacaccagatgggactgccaaggtcacagactttgggattgctgtagcc480 tttgcagagacaagtctgacccagactaactcgatgttgggctcagttcattacttgtca540 ccagagcaggcgcgtggttcgaaggcgactgtgcagagtgatatctatgccatggggatt600 4S attttctatgagatgctgacaggccatatcccttatgacggggatagcgcggtgaccatt660 gccctccagcatttccagaaacccctgccgtccgttattgcagaaaatccatctgtacct720 caggctttagaaaatgttattat,caaggcaactgctaaaaagttgaccaatcgctaccgc780 tcggtttcagagatgtatgtggacttgtctagtagcttgtcctacaatcgtagaaatgaa840 agtaagttaatctttgatgaaacgagcaaggcagataccaagaccttgccgaaggtttct900 50 cagagtaccttgacatctattcctaaggttcaagcgcaaacagaacacaaatcaatcaaa960 aacccaagccaggctgtgacagaggaaacttaccaaccacaagcaccgaaaaaacataga1020 tttaagatgcgttacctgattttgttggccagccttgtattggtggcagcttctcttatt1080 tggatactatccagaactcctgcaaccattgccattccagatgtggcaggtcagacagtt1140 gcagaggccaaggcaacgctcaaaaaagccaattttgagattggtgaggagaagacagag1200 SS gctagtgaaaaggtggaagaagggcggattatccgtacagatcctggcgctggaactggt1260 cgaaaagaaggaacgaaaatcaatttggttgtctcatcaggcaagcaatctttccaaatt1320 agtaattatgtcggtcggaaatcctctgatgtcattgcggaattaaaagagaaaaaagtt1380 ccagataatt tgattaaaat tgaggaagaa gagtcgaatg agagtgaggc tggaacggtc 1440 ctgaagcaaa gtctaccaga aggtacgacc tatgacttga gcaaggcaac tcaaattgtt 1500 ttgacagtag ctaaaaaagc tacgacgatt caattaggga actatattgg acggaactct 1560 acagaagtaa tctcagaact caagcagaag aaggttcctg agaatttgat taagatagag 1620 gaagaagagt ccagcgaaag cgaaccagga acgattatga aacaaagtcc aggtgccgga 1680 acgacttatg atgtgagtaa acctactcaa attgtcttga cagtagctaa aaaagttaca 1740 agtgttgcca tgccgagtta cattggttct agcttggagt ttactaagaa caatttgatt 1800 caaattgttg ggattaagga agctaatata gaagttgtag aagtgacgac agcgcctgca 1860 ggtagtgcag aaggcatggt tgttgaacaa agtcctagag caggtgaaaa ggtagacctc 1920 aataagacta gagtcaagat ttcaatctac aaacctaaaa caacttcagc tactccttaa 1980 <210> 103 <211> 1176 <212> DNA
IS <213> Streptococcus pneumoniae <400> 103 atgaaacattttgatactattgtcatcggtgggggacctgctggtatgatggctacgatt60 tccagtaacttttatggacagaaaaccctcctcatcgaaaaaaatcggaaacttggaaaa120 20aaattagctgggactggtgggggacgttgcaatgtgaccaacaatggtagcttagacaac180 ctgctagctggaattcctggaaacggacgctttctttacagtgttttctcccagttcgat240 aatcatgacatcatcaacttttttacagaaaatggtgttaaacttaaggtcgaagaccac300 ggacgcgtctttccagccagtgacaagtctcggactattatcgaagctttggaaaagaaa360 atcactgaactaggtggtcaagttgctactcaaatagaaatcgtttctgttaaaaaagta420 ~Sgatgaccagtttgtccttaagtcagcggatcaaaccttcacttgtgagaaactcattgtc,480 acaacaggtggtaagtcttatccttcgactggttcgactggttttggtcacgagattgct540 cgccattttaagcataccatcaccgatcttgaggctgctgaaagtcctttattaacagat600 tttccacataaagccttacaagggatttctctggacgatgtgaccctaagttatggtaag660 catgtcatcactcatgatttactctttacccactttggtttgtcaggtcctgctgcccta720 30cgcatgtctagctttgtcaaaggtggggaggttctctcactcgatgttttgcctcaactt780 tctgagaaggacttggttacatttctagaagaaaatcgggaaaaatccttgaaaaacgct840 ttaaaaaccttgttaccagaacgcttggccgaattttttgtacaaggatatcctgaaaaa900 gtcaaacagctgactgaaaaggaacgagaacaacttgtccagtccattaaagaacttaaa960 attcctgtaactggaaaaatgtcccttgcaaagtcctttgttaccaagggtggagtcagt1020 35ctcaaggaaatcaatcctaaaacccttgaaagtaagctggtacctggcctccactttgca1080 ggcgaagttatggatatcaatgcccacacgggtggctttaacatcacttctgccctctgt1140 accggctgggtggcgggaagtctgcattat,gattaa 1176 <210> 104 40 <211> 696 <212> DNA
<213> Streptococcus pneumoniae <400> 104 4S , atgctgaaat gggaagactt gcctgtggaa atgaaatcaa gcgaggttga gtcttactac 60 cagcttgtct ctaaaaggaa gggttcgctg attttcaagc gttgcttgga ctgggttttg 120 gccttggtgc ttacatgggt tctaacttct cccatctttc tcatcttgag catttggatc 180 aagttggata gcaaggggcc agtgatttac aagcaagagc gtgtgaccca gtacaaccgt 240 cggttcaaga tttggaagtt ccgtaccatg gtgacggatg cggataaaaa aggaagtctg 300 50 gtgacttctg ctaacgatag ccgtattacc aaggttggaa atttcatccg acgtgtccgt 360 ttggacgaac tgcctcagtt ggtcaatgtc cttaaaggtg agatgtcctt tgtcggtaca 420 cgacctgaag tgccacgtta tacagagcag tatagccctg aaatgatggc aaccttgctc 480 ttgcaagcag gaattacctc tccagccagc atcaactaca aggatgagga caccatcatc 540 agtcaaatga cggagaaagg tctgtcagtt gatcaggcct atgtggagca tgttcttcct 600 55 gaaaagatgc gctataacct cgcctatctc cgagagttta gtttctttgg ggacatcaaa 660 atcatgtttc aaaccgtgtt tgaggtacta aaataa 696 <210> 105 <211> 423 <2l2> DNA
<213> Streptococcus pneumoniae <400> 105 atgactagtc cac.tattaga atctagacgc caactccgta aatgcgcttt tcaagctctc 60 atgagccttg agttcggtac ggatgtcgaa actgcttgtc gtttcgccta tactcatgat 120 cgtgaatata cggatgtaca acttccagcc tttttgatag acctcgtttc tggtgttcaa 180 1~ gctaaaaagg aagaactaga taagcaaatc actcagcatt taaaagcagg ttggaccatt 240 gaacgcttaa cgctcgtgga gagaaacctc cttcgcttgg gagtctttga aatcacttca 300 tttgacactc ctcagctggt tgctgttaat gaagctatcg agcttgcaaa ggacttctcc 360 gatcaaaaat ctgcccgttt tatcaatgga ctgctcagcc agtttgtaac agaagaacaa 420 taa 423 IS
<210> 106 <211> 3540 <212> DNA
<213> Streptococcus pneumoniae 2,0 <400> 106 atgtatttaaaggaaatcgaaattcaggggttcaagtcttttgctgataagaccaaggtc60 gtttttgaccaaggtgtgacggcagttgttggacccaatggatctggaaagtccaatatt120 acagaaagtctgcgttgggctttgggggagtctagtgtcaaga.gtctccgtgggggcaag180 2,5atgccggatgtcatctttgctggaacagaaagtcgcaaaccgctcaattatgcttctgta240 gttgtgactctggataatcatgacggatttatcaaggatgcaggtcaagaaatcagggtg300 gaacgccatatctatcgtagtggagatagcgaatacaagattgacggcaagaaagtccgt360 ctgcgtgatattcatgacctcttcttggatactggattgggacgagattccttctctatt420 atttcccaagggaaggttgaggagatttttaattccaagcctgaggaacgacgagctatt480 30 tttgaagaagctgctggagttttaaaatacaagactcgcagaaaagaaaccgagagtaaa540 ctgcagcaaactcaggataatctggaccgcttagaggacattatctacgagttggataat600 caaatcaagcctcttgagaagcaagctgagaatgcccgtaagtttttagacttggaagga660 caacgtaaggctatttatttagacgttctggttgctcaaatcaaggaaaataaggcagaa720 ctagagtcgacagaagaagagttggctcaggttcaagaactcttgatgagttattaccaa780 35 aagcgtgaaaaattagaagaagaaaatcaaa-ctcttaaaaagcaacgccaagatttacag840 gctgaaatggccaaagaccaaggcagtttgatggacttgactagtctgattagtgattta900 gaaagaaaattagccctatcgaaactggagtccgagcaagtggccctgaatcaacaggag960 gcacaagctcgtttggctgctttggaggataagagaaattcactcagcaaagaaaagtat1020 gataaagaaagctctttagctctgttagagggaaatctagtccaaaataatcaaaaactc1080 40 aatcgtttagaagctgaattgctggctttctcagacgatcctgatcagatgattgagctc1140 ttacgtgaacgctttgtagctcttttacaagaagaagcggatgtCtcaaaccagttgacc1200 cgtattgagaatgagttggaaaatagtcgtcagctttctcaaaaacaagcagatcaacta1260 gaaaagctgaaagagcaattagctacagctaaagagaaggctagtcagcaaaaagacgag1320 cttgaaactgccaaggtgcaggttcagaaattattggctgactatcaagctattgccaag1380 4S gagcaagaggagcagaaaacttcctatcaagctcaacaaagtcaactctttgaccgtctg1440 gatagtctcaaaaacaagcaggccagagctcaaagtttggaaaatatcctgagaaatcat1500 agtaacttttatgcaggtgttaagagtgttctccaagaaaaagatcgcctaggtgggatt1560 attggtgcagtcagtgagcatctgacctttgatgtttattatcaaactgccctagagatt1620 gccttaggggcaagtagccagcatatcatcgtagaagatgaagagtcggcaaccaaagct1680 50 attgatttcctcaaacgaaacagagtcggtcgtgcaacctttcttcctttgaccactatt1740 aaggcgcgtacgatttctagtcagaaccaagatgctatcgctgtaagcccaggtttcctt1800 gggatggcagatgagttggtgacttttgatactagactggaagccattttcaagaacttg1860 ctagctacgacggctatctttgataccgtagaacatgcgcgtgaagctgctcgacaagtt1920 cgttatcaggttcgtatggtgacattggatgggacagaattacgcacgggtggttcctat1980 SS gcgggtggtgccaatcgccaaaataacagtattttcatcaagccagaactggagcaatta2040 caaaaagaaattgctgcagatgaagcaagcttgggttcagaagaagcggctttgaagacc2100 ttgcaagaccagatggctgcattgacagaaaga~ttagaagccatcaaatctcaaggagag2160 caggcacgtattcaggagcaaggcttgtccctcgcttatcagcaaactagtcagcaagtt2220 gaagaactggaaactctttggaaactccaagaagaggaaatagatcgtctttctgaggga2280 gattggcaagcggataaggaaaaatgtcaagagagccttgctactatcgccagtgacaag2340 caaaatctggaagctgagattgaagaaattaagtctaataaaaacgccatccaagaacgc2400 S tatcaaaatttgcaggaagaggtggcgcaagctcgcttgcttaagacaaaactgcaaggg2460 caaaaacgttatgaagtagctgatattgagcgtttagg,caaggaattggacaatcttaat2520 atcgaacaagaagaaattcagcgcatgctccaagaaaaagttgacaatcttgagaaggtt2580 gatacagaattgctcagtcaacaggcggaagaatccaaaactcagaaaacaaatctccaa2640 caaggtttgattcgcaagcagtttgagttggatgatatagaaggtcaactggatgatatt2700 1~ gccagtcacttggatcaagctcgccagcagaatgaggagtggattcgcaagcaaacacgt2760 gctgaagccaagaaagaaaaggtcagcgagcgcttgcgccatctacaaaatcaattaaca2820 gaccagtaccagattagctatactgaagcactagaaaaggcacatgaattggaaaacctc2880 aatctggcagagcaagaggtgcaggatttagagaaggctattcgctcattgggacctgtc2940 aacttggaagctattgaccagtacgaagaagttcacaaccgtctggactttctaaatagt3000 IS cagcgagatgatattttgtcagcgaaaaatctgctccttgaaaccattacagagatgaat3060 gatgaggtcaaggaacgctttaaatcaacctttgaagctattcgtgagtcctttaaagtg3120 accttcaagcagatgtttggcggaggtcaggcagacttgatattgactgagggcgacctt3180 ttaacagctggtgtggagatttctgttcaacctccaggtaagaaaatccagtcgcttaac3240 ctcatgagtggtggtgaaaaagctctatcggctcttgccttgcttttctccattattcgt3300 gtcaagaccattccttttgtcatcttggatgaggtggaagctgcgctggatgaagccaat3360 gttaaacgttttggggattacctcaaccgctttgacaaggacagccagtttatcgtcgta3420 acccaccgtaagggaaccatggcagcggctgattccatctatggagtgaccatgcaagaa3480 tcaggtgtctcaaaaattgtttcggttaagttaaaagatttagaaagtattgaaggatga3540 25 <210> 107 <211> 1344 <212> DNA

<213> Streptococcus pneumoniae <400> 107 atgacaaaacgtgtaacgattattgacgtaaaagactatgttg,gtcaggaagtgacgatt60 ggcgcttgggttgccaacaaatcaggaaaaggaaaaatcgctttcttacaattgcgtgat120 ggaacagccttctttcaaggtgtggcttttaaaccaaactttgtcgaaaaatttggtgaa180 gaagtgggacttgagaagtttgatgttatcaaacgcttgagccaagaaacgtctgtttat240 3S gtgacaggtattgtcaaagaggacgaacgttctaaatttggctatgagttggacatcaca300 gacatcgaagtgatcggtgaatctcaagactacccaatcacaccaaaagaacacggaaca360 gactttttgatggataaccgtcacttgtggctacgctctcgtaagcaagtagctgtgttg420 caaatncgtaacgctattatctatgcaacttatgagttctttgacaagaacggttttatg480 aagtttgacagcccaattctttcaggaaatgcggcagaagattctacagaactctttgaa540 4~ actgactacttcggaacgccagcctacttgagccaatcaggtcagctttacctagaagca600 ggggctatggctcttggtcgtgtctt'tgactttggtccagttttccgtgctgaaaaatca660 aaaacacgccgtcacttgactgagttctggatgatggatgctgagtactcatacttgaca720 catgatgagtcgcttgacttgcaagaagcttatgtgaaagctcttctacaaggtgttctt780 gaccgcgcgcctcaagccttggaaaccttggaacgtgatacagaactcttgaaacgctac840 45 attgcagagccattcaaacgtatcacttacgatcaagccattgacctcttgcaagagcat900 gaaaatgatgaagatgctgactacgagcatcttgagcatggtgatgactttgggtcacca960 cacgaaacttggatttcaaaccactttggtgtgccaacatttgtcatgaactatccagca1020 gccatcaaggccttctacatgaaaccagttcctggaaatccagagcgcgtgctttgtgca1080 gacttgcttgctccagaaggctat'ggagaaattatcggtgggtctatgcgtgaggaagat1140 50 tacgatgcccttgtcgctaagatggatgaacttggcatggatcgtacagaatatgaattc1200 taccttgaccttcgtaaatacggtacagttccacacggaggatttggtatcggtatcgaa1260 cgtatggtaaccttcgcagcaggaacaaaacatatccgtgaagctattccattcccacgt1320 atgttgcaccgtatcaaaccataa 1344 55 <210> 108 <211> 927 <212> DNA

<213> Streptococcus pneumoniae <400> 108 atgtctgaaaaattagtagaaatcaaagatttagaaatttccttcggtgaaggaagtaag60 aagtttgtcgcggttaaaaatgctaacttctttatcaacaagggagaaactttctcgctt120 gtaggtgagtccggtagtgggaaaacaactattggtcgtgctatcatcggtctaaatgat180 acaagtaatggagatatcatttttgatggtcaaaagattaatggtaagaaatcgcgtgaa240 caagctgcggaattgattcgtcgaatccagatgattttccaagaccctgccgcaagtttg300 aatgaacgtgcgactgttgattatattatttctgaaggtctttacaatcaccgtttattt360 aaggatgaagaagaacgtaaagagaaagttcaaaatattatccgtgaagtaggtcttctt420 gctgagcacttgactcgttaccctcatgaattctcaggcggtcaacgtcaacgtatcggt480 attgcccgtgccttggtcatgcaaccagactttgttattgcagatgagccaatttcagcc540 ttggacgtttctgtacgtgcccaagtcttgaacttgctcaaaaaattccaaaaagagctc600 ggcctgacctatctcttcatcgcccatgacttgtcggttgttcgctttatttcagatcgt660 IS atcgcagttatttacaagggtgttattgtagaggttgcagaaacagaagaattgtttaac720 aatccaattcacccatatactcaagccttgctttcagcggtaccaatcccagatccaatc780 ttggaacgtaagaaggtcttgaaggtttacgacccaagtcaacacgactatgagactgat840 aagccgtctatggtagaaatccgtccaggtcactatgtttgggcgaaccaaaccgaattg900 gcacgttatcaaaaaggactaaactag ~ ' g27 <210> 109 <211> 1275 <212>'DNA
<213> Streptococcus pneumoniae <400> 109 atgaagataagttggaatggattttctaaaaaatcataccaagagcgcctcgagctgcta60 aaagctcaggcgctccttagtcctgagagacaagctagtctggagaaggatgaacagatg120 agtgtgactgtggcagaccagctgagtgagaatgtggtgggaactttttctctgccttat180 tcgctggttccggaggtacttgtcaacggtcaggaatacaccgttccctatgtgacagaa240 gaaccctctgtggttgcggcggccagctatgccagcaaaatcatcaagcgtgcaggtggt300 tttactgcacaagtccatcagcgccagatgattgggcaggtagccctttatcaaattgct360 aatcctaaactagcgcaagagaagattgccagcaagaaagcggagctcttggagcttgcc420 aatcaagcctatccttctatcgttaaacgtgggggtggggcgcgtgatctgcatgtcgag480 cagataaaaggcgaaccagactttctcgttgtttatattcatgtcgatacccaggaagcc540 atgggtgccaatatgctcaacaccatgctggaagccttgaaaccagtcttagaagaactc600 agtcagggacagagtctcatgggaatccttccaactacgcgactgattctctggtgact660 g gcaagctgtcgcatcgcctttcgctacttgagccgccaaaaggatcaaggacgagagatt720 gcggagaaaattgcgttggctagtcagtttgcgcaggctgatccttaccgagctgctact780 cataataaaggaatttttaatggtattgatgcgattttgattgccactggtaatgactgg840 cgtgccatcgaagctggggcccatgcctttgccagtcgagatggacgctatcaaggtctt900 agctgctggacgctggaccttgaaagagaagaattggtcggtgagatgaccctgcccatg960 cctgtagcgactaagggtggctctatcggcctcaacccacgtgtagctctcagtcatgat1020 ctactaggaaatccttctgccagagaattagcccagattatcgtgtccatcggtcttgct1080 caaaattttgcagccctcaaagccttggtaagtacgggcatccagcaaggccacatgaaa1140 ctacaggccaaatccctagctctcctagctggggctagtgaatctgaagttgctccccta1200 gtagagcgcctcatctcagataaaacctttaacctagagacagcccagcgctatctcgaa1260 aatttaagatcataa 1275 <210> 110 <211> 789 <212> DNA
<213> Streptococcus pneumoniae <400> 110 atgccaatta catcattaga aataaaggac aagacttttg gaactcgatt cagaggtttt 60 gatccagaag aagtcgatga atttttagat att gtggttc gtgattacga agatcttgtg 120 cgtgcgaatc atgataaaaa tttgcgtatt aagagtttag aagagcgttt gtcttacttt 180 gatgaaataa aagattcatt gagccagtct gtattgattg ctcaggatac agctgagaga 240 gtgaaacagg cggcgcatga acgttcaaac aatatcattc atcaagcaga gcaagatgcg 300 caacgcttgt tggaagaagc taaatataag gcaaacgaga ttcttcgtca agcaactgat 360 aatgctaaga aagtcgctgt tgaaacagaa gaattgaaga acaagagccg tgtcttccac 420 caacgtctca aatctacaat tgagagtcag ttggctattg ttgaatcttc agattgggaa 480 gatattctcc gtccaacagc tacttatctt caaaccagtg atgaagcctt taaagaagtg 540 gttagcgaag tacttggaga accgattcca gctccaattg aagaagaacc aattgatatg 600 acacgtcagt tctctcaagc agaaatggca gaattacaag ctcgtattga ggtagccgat 660 aaagaattgt ctgaatttga agctcagatt aaacaggaag tggaagctcc aactcctgta 720 gtgagtcctc aagttgaaga agagcctctg ctcatccagt tggcccaatg tatgaagaac 780 cagaagtag 78g <210> 111 IS <211> 1728 <212> DNA
<213> Streptococcus pneumoniae <400> 111 ZO atgtctaatggacaactaatttatttaatggttgcaattgcagtcattttagttctggct60 tatgtagtggcaatctttctacgtaagcgaaacgaggggagattagaggcgctagaagaa120 agaaaagaagaactatacaatcttccagtaaatgatgaagtagaagctgtaaaaaatatg180 cacttgattggacaaagtcaagtggctttccgtgaatggaatcaaaaatgggtcgattta240 tctctcaactcttttgccgatattgaaaataatctctttgaagcagaaggttataaccat300 25 tcatttcgttttctcaaggccagtcatcaaattgaccaaattgagagtcaaattactttg360 attgaagaagatattgcggcaattcgcaatgctttggcagacttagagaagcaagaatct420 aaaaatagtggtcgtgttcttcatgctttggatttatttgaggaacttcagcatagagtt480 gctgaaaattcagaacagtatggtcaagccttggatgaaattgaaaaacaattagaaaat540 atccaatctgaattttcacaatttgtaaccttgaattcatcgggtgaccctgtggaagcc600 3~ gcagtgattttggataatacagaaaatcacattttggccttaagtcatattgtggatcgt660 gttccagccttggttacgacgctttctacagaattgccagatcaattacaggatttggaa720 gccggttatcgtaaactaattgatgctaattatcattttgttgaaacggatattgaagcg780 cgtttccacttgctttatgaagcattcaagaaaaaccaagagaatattcgtcagttggaa840 ttggataatgccgaatatgagaatggacaggcacaagaggaaatcaatgccttgtatgat900 35 atttttactcgagaaattgctgctcagaaagtagtggaaaatctacttgcaactcttcca960 acttaccttcaacatatgaaagagaataatactttattggga~gaagatattgcacgtttg1020 aacaagacctatttacttcctgagacagctgcaagccatgttcgtcgtattcagacagaa1080 ttagagagttttgaggcagctattgttgaggtaacttcaaatcaagaagaaccaacccaa1140 gcttattcagttcttgaagaaaatcttgaggatttacaaactcaactaaaagatattgaa.1200 ~ gatgagcaaatttcagttagtgagcgcctgacacaaattgagaaagatgatattaatgca1260 cgtcaaaaggccaatgtttatgtcaatcgtctccatactatcaagcgatacatggaaaaa1320 cgcaatctgccaggtattccacaaactttcttgaagttattctttacggcaagcaataat1380 accgaggatttaatggttgagttagaacaaaaaatgattaacattgaatctgttacccga1440, gttcttgaaattgcaacgaatgatatggaagctttagaaacggaaacttataatattgta1500 45 caatatgcaactttgacagagcaactcttgcaatattctaaccgctatcgctcatttgat1560 gaacgcattcaagaagcatttaacgaagctttagatatttttgaaaaagaatttgattat1620 cacgcttcatttgataagatttCtcaagcattggaagtggcagagcctggtgtaaccaat1680 cgctttgttacctcatatgagaaaacacgtgaaacgattcgtttttaa 1728 5~ <210> 112 <211> 2403 <212> DNA
<213> Streptococcus pneumoniae SS <400> 112 atgcttatat cttataaatg gttaaaagaa ttggtggaca ttgatgtgcc atcacaagag 60 ttggctgaaa aaatgtcaac tacaggaatc gaggtagagg gtgtcgaatc accagctgct 120 ggtctctcaaaaattgtcgtcggtgaggtcttgtcttgcgaagatgtgccagagactcac180 ctccatgtttgtcaggttaacgttggcgaagaagagcgtcagatcgtttgtggtgcccca240 aatgtgcgtgctgggatcaaggtcatggtggctcttccaggagctcgtatcgctgataac300 tacaaaatcaaaaaaggaaaaatccgtggtttggagtcacttggaatgatctgttcactt360 S ggtgaattgggaatttctgactcagttgtgcctaaggaattcgcagatggcatccaaatc420 ttgcctgaagatgccgtgccaggtgaggaagtcttttcttacctagacttggatgatgaa480 atcatcgaactttccatcacaccaaaccgtgcagatgccctttctatgtgtggagtggct540 cacgaagtggcagccatctatgacaaggcagtcaactttaaagaatttactctaacagaa600 actaatgaagctgcggcagatgccctttctgtcagcattgagacagacaaggcgccttac660 tatgcagctcgtatcttggacaatgtgaccatcgcaccaagtccacaatggttgcaaaac720 cttctcatgaacgaaggaatccgtcccatcaataacgtagtggacgtgaccaactacatc780 ctgctctattttggtcaaccaatgcatgcctttgacttggataactttgaagggactgac840 atccgtgtgcgtgaagcgcgtgctggtgaaaaattggtgaccttggacggtgaagaacgt900 gacttggacgtgaatgacctagtcatcactgtcgcagacaagccagtagcccttgcaggt960 IS gtcatgggtggtcaagcaacagaaatctctgaaaaatctagtcgtgttgtccttgaagct1020 gctgttttcaatggcaaatctatccgtaagacaagtggtcgcctgaaccttcgttctgag1080 tcatcttctcgctttgaaaaaggaattaatgtggcaacagttaatgaagcccttgatgcg1140 gcagctagcctgattgcggaacttgcaggtgcgacggtgcgtaagggcatcgtttcagcg1200 ggtgagcttgatacttcagatgtagaagtttcttcaacccttgctgatgttaaccgtgtc1260 ctcggaactgagctgtcttatgctgatgtagaagacgtcttccgtcgtcttggctttggt1320 ctttctggaaatgcagacagctttacagtcagagtcccacgtcgtcgttgggatatcaca1380 atcgaagctgacctctttgaagaaattgctcgtatctatggttatgaccgcttgccaact1440 agtctaccaaaagacgatggtacagcaggtgaattgacagccacacaaaaactccgccgt1500 caagttcgtactattgctgaaggagcaggtttgacagaaatcatcacctatactctaaca1560 25 actcctgaaaaagcagttgagtttacggctcaaccaagtaaccttacggaactcatgtgg1620 ccaatgactgtggatcgttcagtcctccgtcaaaatatgatttcaggtatccttgatacc1680 gttgcctacaa.cgtggctcgtaagaataaaaacttggccctttacgagattggaaaagtc1740 tttgaacaaacaggtaatccaaaagaagaacttccaaatgaaatcaacagttttgccttt1800 gccttgacaggcttggttgctgaaaaagatttccaaacagcagcagttccagttgatttc1860 30 ttctatgctaagggaatccttgaagccctatttactcgtttgggactccaagtaacctat1920 acagcaacatctgaaatcgctagccttcatccaggtcgtacagccgtgatttcactcggt1980 gaccaagttcttggtttccttggccaagtgcatccagtcactgccaaggcttacgatatt2040 ccagaaacgtatgtggctgagcttaacctttcagctatcgaagctgcgcttcagccagcg2100 actccatttgtagaaatcaccaaattcccggcagtcagccgtgacgttgcccttctcctc2160 35 aaggcagaagtgactcatcaagaagttgtagatgctatccaagctgccggcgtgaaacgt2220 ttgacagatatcaaactctttgacgtcttctcaggtgagaaattgggacttggtatgaag2280 tcaatggcttatagcttgaccttccaaaatccagaagatagcttaacggacgaagaagtc2340 gcacgctatatggaaaaaatccaagcatcgctcgaagaaaaagtcaatgcagaagtgcgt2400 taa 2403 <210> 113 <211> 543 <212> DNA
<213> Streptococcus pneumoniae <400> 113 atgttagaaa acgatattaa aaaagtcctc gtttcacacg atgaaattac agaagcagct 60 a-aaaaactag gtgctcaatt aactaaagat tatgcaggaa aaaatccaat cttagttggg 120 attttaaaag gatctattcc ttttatggct gaattggtca aacatattga tacacatatt 180 gaaatggact tcatgatggt ttctagctac catggtggaa cagcaagtag tggtgttatc 240 aatattaaac aagatgtgac tcaagatatc aaaggaagac atgttctatt tgtagaagat 300 atcattgata caggtcaaac tttgaagaat ttgcgagata tgtttaaagc aagagaagca 360 gcttctgtta aaattgcaac Cttgttggat aaaccagaag gacgtgttgt agaaattgag 420 gcagactata cctgctttac tatcccaaat gagtttgtag taggttatgg tttagactac 480 aaagaaaatt atcgtaatct tccttatatt ggagtattga aagaggaagt gtattcaaat 540 tag 543 <210>

<21 1>

<21 2>
PRT

<21 3> pneumoniae Streptococcus S

<40 0>

Met IleTyrAla GlyIleLeu AlaGly GlyThrGlyThr ArgMetGly ~10Ile SerAsnLeu ProLysGln PheLeu GluLeuGlyAsp ArgProIle Leu IleHisThr IleGluLys PheVal LeuGluProSer IleGluZys Ile ValValGly ValHisGly AspTrp ValLeuHisAla GluAsp.Leu Val AspLysTyr LeuProLeu HisLys GluArgIle21e IleThrLys Gly GlyAlaAsp ArgAsn,ThrSerIle GluAsnIleIle GluAlaIle 85 ' 90 95 ~S Asp AlaTyrArg ProLeuThr ProGlu AspIleValVal ThrHisAsp Ser ValArgPro PheI1eThr .LeuArg MetIleGlnAsp SerIleLys Leu AlaGlnAsn HisAspAla ValAsp ThrVa1ValGlu AlaVa1Asp Thr IleValGlu SerThrAsn GlyGln PheI1eThrGly IleProAsn Arg AlaHisLeu TyrGlnGly GlnThr ProGlnThrPhe ArgCysLys 40 Asp PheMetAsp LeuTyrGly SerLeu SerAspGluGlu LysGluIle Leu ThrAspAla CysLysIle PheVal IleLysGlyLys AspValAla Leu AlaLysGly GluTyrSer AsnLeu LysIleThrThr ValThrAsp Leu LysIleAla LysSerMet IleGlu LysAsp <210> 115 <211> 185 SS <212> PRT
<213> Streptococcus pneumoniae <400> 115 Met Ala Asn Val Ile Ile Glu Lys Ala Lys Glu Arg Met Thr Gln Ser 1 ~ 5 10 15 $ His Gln Ser Leu Ala Arg Glu Phe Gly Gly Ile Arg Ala Gly Arg Ala Asn Ala Ser Leu Leu Asp Arg Val His Val Glu Tyr Tyr Gly Val Glu Thr Pro Leu Asn Gln Ile Ala Ser Tle Thr I1e Pro Glu Ala Arg Val Leu LeuValThr ProPheAsp LySSerSer LeuLysAsp IleGluArg Ala LeuAsnAla SerAspLeu GlyIleThr ProAlaAsn AspGlySer Val IleArgLeu ValIlePro AlaLeuThr GluGluThr ArgArgAsp 100 105 110' Leu AlaLysG1u ValLysLys ValGlyGlu AsnAlaLys ValAlaVal Arg AsnIleArg ArgAspAla MetAspGlu AlaLysLys GlnG1uLys 130 ~ 135 140 Ala GlnGluIle ThrGluAsp GluLeuLys ThrLeuGlu LysAspIle 3~ 145 150 155 160 Gln LysValThr AspAspAla ValLysHis IleAspAsp MetThrAla Asn LysGluLys GluLeuLeu GluVa1 <210> 116 ~ <211> 450 <212> PRT

<213> Streptococcus pneumoniae <400> 116 Met Gly Tyr PheGlyThrAsp GlyValArg GlyGlu AlaAsnLeu Lys Glu Leu Pro GluLeuAlaPhe LysLeuGly ArgPhe GlyGlyTyr Thr Val Leu Gln HisGluThrGlu AlaProLys ValPhe ValGlyArg Ser Asp Thr Ile SerGly.GluMet LeuGluSer AlaLeu ValAlaGly Arg Leu Leu Val GlyIleHisVal TyrLysLeu GlyVal LeuAlaThr Ser Pro Ala Val Ala Tyr Leu Val Glu Thr Glu Gly Ala Ser Ala Gly Val Met Ile Ser Ala Ser His Asn Pro Ala Leu Asp Asn Gly Ile Lys Phe 100 l05 ~ 110 Phe Gly Gly Asp Gly Phe Lys Leu Asp Asp Glu Lys Glu Ala Glu Ile Glu Ala Leu Leu Asp Ala Glu Glu Asp Thr Leu Pro Arg Pro Ser Ala Glu Gly Leu Gly Ile Leu Val Asp Tyr Pro Glu Gly Leu Arg Lys Tyr Glu Gly Tyr Arg Val Ser Thr Gly Thr Pro Leu Asp Gly Met Lys Val A1a Leu Asp Thr Ala Asn Gly AIa Ala Ser Thr Ser Ala Arg Gln Ile Phe Ala Asp Leu G1y Ala Gln Leu Thr Val Ile Gly Glu Thr Pro Asp Gly Leu Asn Ile Asn Leu Asn Val Gly Ser Thr His Pro Glu Ala Leu Gln Glu Val Val Lys Glu Ser Gly Ser Ala Ile Gly Leu Ala Phe Asp Gly Asp Ser Asp Arg Leu Ile Ala Val Asp Glu Asn Gly Asp I1e Val Asp Gly Asp Lys Ile Met Tyr Ile Ile Gly Lys Tyr Leu Ser Glu Lys 260 265 _ 270 Gly Gln Leu Ala Gln Asn Thr Tle Val Thr Thr Val Met Ser Asn Leu Gly Phe His Lys Ala Leu Asn Arg Glu Gly Ile Asn Lys Ala Val Thr Ala Val Gly Asp Arg Tyr Val Val Glu Glu Met Arg Lys Ser Gly Tyr Asn Leu Gly Gly Glu Gln Ser Gly His Val Ile Leu Met Asp Tyr Asn Thr Thr Gly Asp .Gly Gln Leu Ser Ala Val Gln Leu Thr Lys Ile Met Lys Glu Thr Gly Lys Ser Leu Ser Glu Leu Ala Ala Glu Val Thr Ile SS 355 360 365' Tyr Pro Gln Lys Leu Val Asn Ile Arg Val Glu Asn Val Met Lys Glu Lys Ala Met Glu Val Pro Ala Ile Lys Ala Ile Ile Glu Lys Met Glu G1u Glu Met Ala Gly Asn Gly Arg Ile Leu Val Arg Pro Ser Gly Thr 405 410 415 .
Glu Pro Leu Leu Arg Val Met Ala Glu Ala Pro Thr Thr G1u Glu Val Asp Tyr Tyr Val Asp Thr Ile Thr Asp Val Val Arg Ala Glu Ile Gly IS I1e Asp <210> 117 <211> 234 <212> PRT
<213> Streptococcus pneumoniae <400> 117 ~5 Met Lys Lys Ile Leu Ile Val Asp Asp Glu Lys Pro I1e Ser Asp Ile Ile Lys Phe Asn Met Thr Lys Glu Gly Tyr Glu Val Val Thr Ala Phe Asn Gly Arg Glu Ala Leu Glu Gln Phe G1u Ala Glu Gln Pro Asp Ile Ile Ile Leu Asp Leu Met Leu Pro Glu Ile Asp Gly Leu Glu Val Ala Lys Thr Ile.Arg Lys Thr Ser Ser Val Pro Ile Leu Met Leu Ser Ala Lys Asp Ser Glu Phe Asp Lys Val Ile Gly Leu Glu Leu Gly Ala Asp Asp Tyr Val Thr Lys Pro Phe Ser Asn Arg Glu Leu Gln Ala Arg Val Lys Ala Leu Leu Arg Arg Ser Gln Pro Met Pro Val Asp Gly Gln Glu Ala Asp Ser Lys Pro Gln Pro Ile Gln Ile Gly Asp Leu Glu Ile Val Pro.Asp Ala Tyr Val Ala Lys Lys Tyr Gly Glu Glu Leu Asp Leu Thr His Arg Glu Phe Glu Leu Leu Tyr His Leu Ala Ser His Thr Gly Gln Val Ile Thr Arg Glu His Leu Leu Glu Thr Val Trp Gly Tyr Asp Tyr Phe Gly,Asp Val Arg Thr Val Asp Val Thr Val Arg Arg Leu Arg Glu 195 ~ 200 205 Lys Ile Glu Asp Thr Pro Ser Arg Pro Glu Tyr Ile Leu Thr Arg Arg Gly Val Gly Tyr Tyr Met Arg Asn Asn Ala <210> 118 <211> 368 <212> PRT
<213> Streptococcus pneumoniae <400> 118 Met Glu Glu Ile Leu Cys Ile Gly Cys~Gly Ala Thr Ile G1n Thr Thr Asp Lys Ala Gly Leu Gly Phe Thr Pro Gln Ser Ala Leu Glu Lys Gly Leu Glu Thr Gly Glu Val Tyr Cys Gln Arg Cys Phe Arg Leu Arg His Tyr Asn Glu Ile Thr Asp Va1 Gln Leu Thr Asn Asp Asp Phe Leu Lys Leu Leu His Glu Val Gly Asp Ser Asp Ala Leu Val,Val Asn Val Ile 65 70 75 g0 3$ Asp Ile Phe Asp Phe Asn Gly Ser Val Tle Pro Gly Leu Pro Arg Phe Val Ser Gly Asn Asp Val Leu Leu Val Gly Asn Lys Lys Asp Ile Leu Pro Lys Ser Val Lys Ser Gly Lys Ile Ser Gln Trp Leu Met Lys Arg Ala His Glu Glu Gly Leu Arg Pro Val Asp Val Val Leu Thr Ser Ala 4$ 130 135 140 Gln Asn Lys His Ala Ile Lys Glu Va1 Ile Asp Lys Ile Glu His Tyr $0 Arg Lys Gly Arg Asp Val Tyr Val Val Gly Val Thr Asn Val Gly Lys Ser Thr Leu Ile Asn Ala Ile Ile Gln Glu Ile Thr Gly Asp Gln Asn Va1 Ile Thr Thr Ser Arg Phe Pro Gly Thr Thr Leu Asp Lys Ile Glu Ile ProLeuAsp AspGlySer TyrIleTyr AspThrPro GlyIleIle His ArgHisGln MetAlaHis TyrLeuThr AlaLysAsn LeuLysTyr Val SerProLys LysGluIle LysProLys ThrTyrGln LeuAsnPro Glu GlnThrLeu PheLeuGly GlyLeuGly ArgPheAsp PheIleAla Gly GluLysGln GlyPheThr AlaPhePhe AspAsnGlu LeuLysLeu .

His ArgSerLys LeuGluGly AlaSerAla PheTyrAsp LysHisLeu 20Gly ThrLeuLeu ThrProPro AsnSerLys GluLysGlu AspPhePro Arg LeuValGln HisValPhe ThrIleLys AspLysThr AspLeuVal Ile SerGlyLeu GlyTrpI1e ArgValThr GlyThrAla LysValAla Val TrpAlaPro GluGlyVal AlaValVal ThrArgLys AlaIleIle <210> 119 <21l> 486 <212> PRT
<213> Streptococcus pneumoniae <400> 119 Met Tyr Pro Asp Asp Ser Leu Thr Leu His Thr Asp Leu Tyr Gln Tle l 5 10 15 Asn Met Met Gln Val Tyr Phe Asp Gln Gly Ile His Asn Lys Lys Ala Val Phe Glu Val Tyr Phe Arg Gln Gln Pro Phe Lys Asn Gly Tyr Ala SO
Val Phe Ala Gly Leu Glu Arg Ile Val Asn Tyr Leu Glu Asp Leu Arg Phe Ser Asp Ser Asp Ile Ala Tyr Leu Glu Ser Leu Gly Tyr His Gly Ala Phe Leu Asp Tyr Leu Arg Asn Phe Lys Leu Glu Leu Thr Val Arg Ser Ala Gln Glu Gly Asp Leu Val Phe Ala Asn Glu Pro Ile Val Gln Val Glu Gly Pro Leu Ala Gln Cys Gln Leu Val Glu Thr Ala Leu Leu Asn Ile Val Asn Tyr Gln Thr Leu Val Ala Thr Lys Ala Ala Arg Ile Arg Ser Val Ile Glu Asp Glu Pro Leu Met Glu Phe Gly Thr Arg Arg l45 150 155 160 IS Ala Gln Glu Thr Asp Ala Ala Ile Trp Gly Thr Arg Ala Ala Val Ile Gly Gly Ala Asn Gly Thr Ser Asn Val Arg Ala Gly Lys Leu Phe Asp Ile Pro Val Leu Gly Thr His Ala His Ala Leu Val Gln Val Tyr Gly Asn Asp Tyr Glu Ala Phe Lys Ala Tyr Ala Ala Thr His Lys Asn Cys Val Phe Leu Val Asp Thr Tyr Asp Thr Leu Arg Ile Gly Val Pro Ala Ala Ile Gln Va1 Ala Arg Glu Leu Gly Asp Gln Ile Asn Phe Met Gly Val Arg Ile Asp Ser Gly Asp Ile A1a Tyr Ile Ser Lys Lys Val Arg Gln Gln Leu Asp Glu Ala G1y Phe Thr Glu Ala Lys Ile Tyr Ala Ser Asn Asp Leu Asp Glu Asn Thr Ile Leu Asn Leu Lys Met Gln Lys Ala Lys Ile Asp Val Trp Gly Val Gly Thr Gln Leu Ile Thr Ala Tyr Asp Gln Pro Ala Leu Gly Ala Val Tyr Lys Ile Val Ala Ile Glu Asp Glu Thr Gly Gln Met Arg Asn Thr Ile Lys Leu Ser As.n Asn Ala Glu Lys Val Ser Thr Pro Gly Lys Lys Gln Val Trp Arg Ile Thr Ser Arg Glu Lys~Gly Lys Ser Glu Gly Asp Tyr Ile Thr Tyr Asp Gly Val Asp Ile Ser Asp Met Thr Glu Ile Lys Met Phe His Pro Thr .Tyr Thr Tyr Ile gg .

Lys Lys Thr Val Arg Asn Phe Asp Ala Val Pro Leu Leu Val Asp Ile Phe Lys Glu Gly Ile Leu Val Tyr Asn Leu Pro Ser Leu Thr Asp Ile Gln Asp Tyr Ala Arg Lys Glu Phe Asp Lys Leu Trp Asp Glu Tyr Lys Arg Val Leu Asn Pro Gln His Tyr Pro Val Asp Leu Ala Arg Asp Val IS ~Trp Gln Asp Lys Met Asp Leu Ile Asp Lys Met Arg Lys Glu Ala Leu 465 . 470 475 480 Gly Glu Gly Glu Glu Glu <210> 120 <211> 283 <212> PRT

25<213> Streptococcus pneumoniae <400> 120 Met Ala Ile GlnTrp Phe GlyHis Met Ser AlaArg Thr Pro Lys Arg Gln Val Glu AsnLeu Lys ValAsp Phe Val IleLeu G1n Phe Thr Val 20 ~ 2 5 30 Asp Ala Leu ProLeu Ser GlnAsn Pro Met ThrLys Arg Ser Leu Ile 3$35 40 45 Val Gly Asp Lys Pro Lys Leu Leu Ile Leu Asn Lys Ala Asp Leu Ala 40Asp ProAlaMet ThrLysGlu TrpArgGln TyrPheGlu SerGlnGly 65 70 75 ~ ' Ile GlnThrLeu AlaIleAsn SerLysGlu GlnValThr ValLysVa1 85 ' 90 95 Val ThrAspAla AlaLysLys LeuMetAla AspLysIle AlaArgGln Lys GluArgGly IleGlnIle GluThrLeu ArgThrMet IleIleGly Ile ProAsnAla GlyLysSer ThrLeuMet AsnArgLeu AlaGlyLys 55Lys IleAlaVal ValGlyAsn LysProGly ValThrLys GlyGlnGln Trp Leu Lys Thr Asn Lys Asp Leu Glu Ile Leu Asp Thr Pro Gly Ile l65 170 175 Leu TrpPro LysPheGlu AspGlu ThrValAla LeuLysLeu AlaLeu Thr GlyAla IleLysAsp GlnLeu LeuProMet AspGluVal ThrIle Phe GlyIle AsnTyrPhe LysGlu HisTyrPro GluLysLeu AlaGlu Arg PheLys GlnMetLys IleGlu GluGluPro SerValIle IleMet 225 230 , 235 240 Asp MetThr ArgAlaLeu GlyPhe ArgAspAsp TyrAspArg PheTyr Ser LeuPhe ValLysGlu ValArg AspGlyLys LeuGlyAsn TyrThr 260' 265 270 Leu AspThr LeuGluAsp LeuAsp GlyAsnAsp <210> l21 <211> 156 <212> PRT

<213> Streptococcus pneumoniae <400> 121 Met Ile AsnVa1 Va1LeuVal GlyArgMet ThrArgAspAla G1u Asn 1 5 , 10 15 Leu Arg ThrPro SerAsnVal AlaValAla ThrPheThrLeu Ala Tyr Val Asn ThrPhe LysSerGln AsnGlyGlu ArgGluAlaAsp Phe Arg Ile Asn ValMet TrpArgGln GlnAlaGlu AsnLeuAlaAsn Trp Val Ala Lys Lys Gly Ser Leu Ile Gly Val Thr Gly Arg Ile Gln Thr Arg Ser TyrAsp AsnGln GlnGlyGln ArgValTyr ValThrGlu ValVal $0 Ala GluAsn PheGln MetLeuGlu.SerArgSer ValArgGlu GlyHis 100 105 110' Thr GlyGly AlaTyr SerAlaPro ThrA1aAsn TyrSerAla .ProThr l15 120 125 Asn SerVal ProAsp PheSerArg,AsnGluAsn ProPheGly AlaThr ~. 57 Asn Pro Leu Asp Ile Ser Asp Asp Asp Leu Pro Phe <210> l22 <211> 324 <212> PRT
<213> Streptococcus pneumoniae <400> 122 Met Lys Thr Arg Ile Thr Glu Leu Leu Lys Ile Asp Tyr Pro Ile Phe 1$ Gln Gly Gly Met Ala Trp Val Ala Asp Gly Asp Leu Ala G1y Ala Val Ser Lys Ala Gly Gly Leu Gly Ile Ile Gly Gly G1y Asn Ala Pro Lys Glu Va1 Val Lys Ala Asn Ile Asp Lys Ile Lys Ser Leu Thr Asp Lys 50 55 ~ 60 Pro Phe Gly Val ~Asn Ile Met Leu Leu Ser Pro Phe Val G1u Asp Ile Va1 Asp Leu Val Ile Glu Glu Gly Val Lys Val Val Thr Thr Gly Ala Gly Asn Pro Ser Lys Tyr Met Glu Arg Phe His Glu Ala G1y Ile Ile Val Ile Pro Val Val Pro Ser Val Ala Leu Ala Lys Arg Met Glu Lys 115 . 120 125 Ile Gly Ala Asp Ala Val Ile Ala Glu Gly Met Glu Ala Gly Gly His Ile Gly Lys Leu Thr Thr Met Thr Leu Val Arg Gln Val Ala Thr Ala ~0 145 150 155 160 Ile Ser Ile Pro Val Ile Ala Ala Gly Gly Ile Ala Asp Gly Glu Gly Ala Ala Ala Gly Phe Met Leu Gly Ala Glu Ala Val Gln Val Gly Thr Arg Phe Val Val Ala Lys Glu Se.r Asn Ala His Pro Asn Tyr Lys Glu ' Lys Ile Leu Lys Ala Arg Asp Tle Asp Thr Thr Ile Ser Ala Gln His 210 215 ~ 220 Phe Gly His Ala Val Arg Ala Ile Lys Asn Gln Leu Thr Arg Asp Phe Glu Leu Ala Glu Lys Asp Ala Phe Lys Gln Glu Asp Pro Asp Leu Glu Ile Phe Glu Gln Met Gly Ala Gly Ala Leu Ala Lys Ala Val Val His Gly Asp Va1 Glu Gly Gly Ser Val Met Ala Gly Gln Ile Ala Gly Leu Val Ser Lys Glu Glu Thr Ala Glu-Glu Ile Leu Lys Asp Leu Tyr Tyr Gly Ala Ala Lys Lys Ile Gln Glu Glu Ala Ser Arg Trp Thr Gly Val IS Val Arg Asn Asp <210> 123 <211> 140 <212> PRT

<213> Streptococcus pneumoniae <400> 123 25Met Ile Ile GlnGlyIle LysGluAla LeuProHis ArgTyrPro Asp Met Le.u Val AspArgVal LeuGluVal SerGluAsp ThrIleVal Leu Ala Ile Asn ValThrIle AsnGluPro PhePheAsn GlyHisPhe Lys Pro Gln Pro ValMetPro GlyValLeu IleMetGlu AlaLeuAla Tyr Gln_Thr Gly ValLeuGlu LeuSerLys ProGluAsn LysGlyLys Ala 40Leu Val Tyr AlaGlyMet AspLysVal LysPheLys LysGlnVal Phe Val Pro Asp GlnLeuVal MetThrAla ThrPheVal LysArgArg Gly Gly Thr Ala ValValGlu AlaLysAla GluValAsp GlyLysLeu Ile Ala Ala Gly ThrLeuThr PheAlaIle GlyAsn Ser <210> 124 <211> 340 5 <212> PRT
<213> Streptococcus pneumoniae <400> 124 Met Ile Asn Gln Ile Tyr Gln Leu Thr Lys Pro Lys Phe Ile Asn Val Lys Tyr Gln Glu G1u Ala Ile Asp Gln Glu Asn His Ile Leu Ile Arg Pro Asn Tyr Met Ala Val Cys His Ala Asp Gln Arg Tyr Tyr Gln Gly Lys Arg Asp Pro Lys Ile Leu Asn Lys Lys Leu Pro Met Ala Met Ile His Glu Ser Cys Gly Ile Val Ile Ser Asp Pro Ser Gly Thr Tyr Glu IS 65 70 ~ 75 80 Val Gly Gln Lys Val Val Met Ile Pro Asn Gln Ser Pro Met Gln Ser Asp Glu Glu Phe Tyr Glu Asn Tyr Met Thr Gly Thr His Phe Leu Ser Ser Gly Phe Asp Gly Phe Met Arg Glu Phe Val Ser Leu Pro Lys Asp ZS
Arg Val Val Ala Tyr Asp Ala Ile Glu Asp Thr Val Ala Ala Ile Thr Glu Phe Val Ser Val Gly Met His A1a Met Asn Arg Leu Leu Thr Leu Ala His Ser Lys Arg Glu Arg Ile Pro Val Ile Gly Asp Gly Ser Leu 3$ Ala Phe Val Val Ala Asn Ile Ile Asn Tyr Thr Leu Pro Glu Ala Glu Ile Val Val Ile Gly Arg His Trp Glu Lys Leu Glu Leu Phe Ser Phe A1a Lys Glu Cys Tyr Ile Thr Asp Asn Ile Pro Glu Glu Leu,Ala Phe 210 215 ° 220 Asp His Ala Phe Glu Cys Cys Gly Gly Asp Gly Thr Gly Pro Ala Ile Asn Asp Leu Ile Arg Tyr Ile Arg Pro Gln Gly Thr Ile Leu Met Met Gly Val Ser Glu Tyr Lys Val Asn Leu Asn Thr Arg Asp Ala Leu Glu Lys Gly Leu Leu Leu Val Gly Ser Ser Arg Ser Gly Arg Ile Asp Phe Glu Asn Ala Ile Gln Met Met Lys Val Lys Lys Phe Ala Asn Arg Leu Lys Asn Ile Leu Tyr Leu Glu Glu Pro Val Arg Glu Tle Lys Asp Ile $ His Arg Val Phe Ala Thr Asp Leu Asn Thr Ala Phe Lys Thr Val Phe Lys Trp Glu Val <210> 125 <211> 447 <212> PRT
IS <213> Streptococcus pneumoniae <400> 125 Met Asn Leu Lys Thr Thr Leu Gly Leu Leu Ala Gly Arg Ser Ser His Phe Val Leu Ser Arg Leu Gly Arg Gly Ser Thr Leu' Pro Gly Lys Val Ala Leu Gln Phe Asp Lys Asp Ile Leu G1n Asn Leu Ala Lys Asn Tyr Glu Ile Val Val Val Thr Gly Thr Asn Gly Lys Thr Leu Thr Thr Ala Leu Thr Val Gly Ile Leu Lys Glu Val Tyr Gly Gln Val Leu Thr Asn Pro Ser Gly Ala Asn Met Ile Thr Gly Ile Ala Thr Thr Phe Leu Thr A1a Lys Ser Ser Lys Thr Gly Lys Asn Ile Ala Val Leu G1u Ile Asp Glu Ala Ser Leu Ser Arg Ile Cys Asp Tyr Ile Gln Pro Ser Leu Phe 115 ~ 120 125 Val I1e Thr Asn Ile Phe Arg Asp Gln Met Asp Arg Phe Gly Glu Ile Tyr Thr Thr Tyr Asn Met Ile Leu Asp Ala Ile Arg Lys Val Pro Thr Ala Thr Val Leu Leu Asn Gly Asp Ser.Pro Leu Phe Tyr Lys Pro Thr l65 170 l75 Ile Pro Asn Pro Ile Glu Tyr Phe Gly Phe Asp Leu Glu Lys Gly Pro Ala Gln Leu Ala His Tyr Asn Thr Glu Gly I1e Leu Cys Pro Asp Cys SS 195 200. 205 Gln Gly Ile Leu Lys Tyr Glu His Asn Thr Tyr Ala Asn Leu Gly Ala Tyr IleCys GluGlyCys GlyCysLys Arg.ProAsp LeuAspTyr Arg Leu ThrLys LeuValGlu LeuThrAsn AsnArgSer ArgPheVal Ile Asp GlyGln GluTyrGly IleGlnIle GlyGlyLeu TyrAsnIle ~Tyr Asn AlaLeu AlaAlaVal AlaTleAla ArgPheLeu GlyAlaAsp Ser Gln LeuIle LysGlnGly PheAspLys SerArgAla ValPheGly Arg Gln GluThr PheHisIle GlyAspLys GluCysThr LeuValLeu Ile Lys AsnPro ValGlyAla ThrGlnAla IleGluMet IleLysLeu A1a Pro TyrPro PheSerLeu SerValLeu LeuAsn~Ala AsnTyrAla Asp Gly IleAsp ThrSerTrp TleTrpAsp AlaAspPhe GluGlnIle Thr Asp MetAsp IleProGlu IleAsnAla GlyGlyVal ArgHisSer Glu ' 370 375 380 Ile AlaArg ArgLeuArg ValThrGly TyrProAla GluLysIle Thr Glu ThrSer AsnLeuGlu GlnValLeu LysThrIle GluAsnGln Asp Cys LysHis AlaTyrIle LeuAlaThr TyrThrAia MetLeuG1u Phe Arg GluLeu LeuAlaSer ArgG1nIle ValArgLys GluMetAsn <210> 126 <211> 260 <212> PRT
<213> Streptococcus pneumoniae <400> 126 Met Val Tyr Thr Ser Leu Ser Ser Lys Asp Gly Asn Tyr Pro Tyr Gln S$ Leu Asn Tle Ala His Leu Tyr Gly Asn.Leu Met Asn Thr Tyr Gly Asp Asn GlyAsn IleLeuMet LeuLys TyrValA1aGlu LysLeuG1y Ala His ValThr ValAspIle ValSer LeuHisAspAsp PheAspGlu Asn His TyrAsp IleAlaPhe PheGly GlyGlyGlnAsp PheGluGln Ser Ile IleAla AspAspLeu ProAla LysLysGluSer IleAspAsn Tyr Ile GlnAsn AspGlyVal ValLeu AlaIleCysGly Gly~PheG1n Leu Leu GlyGln TyrTyrVal GluAla SerGlyLysArg IleGluGly Leu Gly ValMet G1yHisTyr ThrLeu AsnGlnThrAsn AsnArgPhe Ile , 130 135 140 G1y AspIle LysIleHis AsnGlu AspPheAspGlu ThrTyrTyr Gly Phe GluAsn HisGlnGly ArgThr PheLeuSerAsp AspGlnLys Pro Leu GlyGln ValValTyr GlyAsn GlyAsnAsnGlu G1uLysVal Gly Glu GlyVal HisTyr.Lys AsnVal PheGlySerTyr PheHisGly Pro Ile LeuSer ArgAsnAla AsnLeu AlaTyrArgLeu ValThrThr Ala Leu LysLys LysTyrGly GlnAsp IleGlnLeuPro AlaTyrGlu Asp Ile LeuSer GlnGluIle AlaGlu GluTyrSerAsp ValLysSer Lys Ala Asp Phe Ser <210> 127 <211> 223 <212> PRT
<213> Streptococcus pneumoniae <400> 127 Met Asn Val Lys Glu Asn Thr G1u Leu Val Phe Arg Glu Val Ala Glu Ala Ser Leu Ser Ala Asn Arg Glu Ser Gly Ser Val Ser Val Ile Ala Val Thr Lys Tyr Va1 Asp Val Pro Thr Ala Glu Ala Leu Leu Pro Leu 35 40 45' Gly Val His His Ile Gly Glu Asn Arg Val Asp Lys Phe Leu Glu Lys Tyr Glu Ala Leu Lys Asp Arg Asp Val Thr Trp His Leu Ile Gly Thr Leu Gln Arg Arg Lys Val Lys Asp Val Ile Gln Tyr Val Asp Tyr Phe His Ala Leu Asp Ser Val Lys Leu Ala Gly Glu Ile Gln Lys Arg Ser 1$ 100 105 110 Asp Arg Val Ile Lys Cys Phe Leu Gln Val Asn Ile Ser Lys G1u Glu Ser Lys His Gly Phe Ser Arg Glu Glu Leu Leu Glu Ile Leu Pro Glu l30 135 140 Leu Ala Gly Leu Asp Lys Ile Glu Tyr Val Gly Leu Met Thr Met Ala Pro Phe Glu Ala Ser Ser Glu Gln Leu Lys Glu Ile Phe Lys Ala Ala Gln Asp Leu Gln Arg Glu Ile Gln Glu Lys Gln I1e Pro Asn Ile Pro Met Thr Glu Leu Ser Met Gly Met Ser Arg Asp Tyr Lys Gla Ala Ile Gln Phe Gly Ser Thr Phe Val Arg Ile Gly Thr Ser Phe Phe Lys <210> 128 <211> 279 <212> PRT
<213> Streptococcus pneumoniae <400> 128 Met Gly Ile Ala Leu Glu Asn Val Asn Phe Thr Tyr Gln Glu Gly Tlir Pro Leu Ala Ser Ala Ala Leu Ser Asp Val Ser Leu Thr Ile Glu Asp Gly Ser Tyr Thr Ala Leu Ile Gly His Thr Gly Ser Gly Lys Ser Thr Ile,Leu Gln Leu Leu Asn Gly Leu Leu Val Pro Ser Gln Gly Ser Val Arg Val Phe Asp Thr Leu,Ile Thr Ser Thr Ser Lys Asn Lys Asp Ile Arg Gln Ile Arg Lys Gln Val Gly Leu Val Phe Gln Phe A1a Glu Asn Gln Ile Phe G1u Glu Thr Val Leu Lys Asp Val Ala Phe Gly Pro Gln Asn Phe Gly Val Ser Glu Glu Asp Ala Val Lys Thr Ala Arg G1u Lys Leu Ala Leu Val Gly Ile Asp Glu Ser Leu Phe Asp Arg Ser Pro Phe I5~ Glu Leu Ser Gly Gly G1n Met Arg Arg Val Ala Ile Ala Gly Ile Leu 145 150 l55 160 Ala Met Glu Pro Ala Ile Leu Val Leu Asp Glu Pro Thr Ala Gly Leu Asp Pro Leu G1y Arg Lys Glu Leu Met Thr Leu Phe Lys Lys Leu His Gln Ser Gly Met Thr Ile Val Leu Val Thr His Leu Met Asp Asp Val_ Ala Glu Tyr Ala Asn Gln Va1 Tyr Val Met G1u Lys Gly Arg Leu Va1 30 Lys Gly Gly Lys Pro Ser Asp Val Phe Gln Asp Val Val Phe Met Glu Glu Val Gln Leu Gly Val Pro Lys Ile Thr Ala Phe Cys Lys Arg Leu Ala Asp Arg Gly Val Ser Phe Lys Arg Leu Pro Val Lys I1e Glu Glu Phe Lys Glu Ser Leu Asn Gly <210> 129 <211> 309 <212> PRT
<213> Streptococcus pneumoniae <400> 129 Met Asp Ile Gln Phe Leu Gly Thr Gly Ala Gly Gln Pro Ser Lys Ala 1 5 10 ~ 15 Arg Asn Val Ser Ser.Leu Ala Leu Lys Leu Leu Asp Glu Ile Asn Glu 20 . 25 30 Val Trp Leu Phe Asp Cys Gly Glu Gly Thr Gln Asn Arg Ile Leu Glu Thr Thr Ile Arg Pro Arg Lys Val Ser Lys Ile Phe Ile Thr His Leu His Gly Asp His Ile Phe Gly Leu Pro Gly Phe Leu Ser Ser Arg Ala Phe Gln Ala Asn Glu Glu Gln Thr Asp Leu Glu Ile Tyr Gly Pro Gln 85 90 g5 Gly Ile Lys Ser Phe Val Leu Thr Ser Leu Arg Val Ser Gly Ser Arg Leu Pro Tyr Arg Ile His Phe His Glu Phe Asp Gln Asp Ser Leu Gly Lys Ile Leu Glu Ile Asp Lys Phe Thr Val Tyr Ala Glu Glu Leu Asp His Thr Ile Phe Cys Val Gly Tyr Arg Val Met. Gln Lys Asp Leu Glu Gly Thr Leu Asp Ala Glu Lys Leu Lys Ala Ala Gly Val Pro Phe Gly Pro Leu Phe Gly Lys Ile Lys Asn Gly Gln Asp Leu Val Leu Glu Asp Gly Thr Glu I1e Lys Ala Ala Asp Tyr Ile Ser Ala Pro Arg Pro Gly Lys Ile Ile Thr Ile Leu Gly Asp Thr Arg Lys Thr Asp Ala Ser Val Arg Leu Ala Val Asn Ala Asp Val Leu Val His Glu Ser Thr Tyr Gly 3$ 225 230 235 240 Lys Gly Asp Glu Lys Ile Ala Arg Asn His Gly His Ser Thr Asn Met Gln Ala Ala Gln Val Ala Val Glu Ala Gly Ala Lys Arg Leu Leu Leu Asn His Ile Ser Ala Arg Phe Leu Ser Lys Asp Ile Ser Lys Leu Lys Lys Asp Ala Ala Thr Ile Phe Glu Asn Val His Val Va1 Lys Asp Leu Glu Glu Val Glu Ile <210> 130 <211> 553 <212> PRT
<213> Streptococcus pneumoniae <400>

Met SerAsnIle SerLeuThr ThrLeuGly GlyValArg GluAsnGly Lys AsnMetTyr IleAlaGlu IleGlyGlu SerIlePhe ValLeuAsn Val GlyLeuLys TyrProGlu AsnGluGln LeuGlyVal AspValVal Ile ProAsnMet AspTyrLeu PheGluAsn SerAspArg IleAlaGly Val PheLeuThr HisGlyHis AlaAspAla IleGlyAla LeuProTyr Leu LeuAlaGlu AlaLysVal ProValPhe GlySerGlu LeuThrIle Glu Leu Ala Lys Leu Phe Val Lys Gly Asn Asp Ala Val Lys Lys Phe Asn AspPheHis ValIleAsp GluAsn ThrGluIleAsp PheGly Gly Thr ValValSer PhePhePro ThrThr TyrSerValPro GluSer Leu Gly IleValLeu LysThrSer GluGly SerIleValTyr ThrGly Asp Phe LysPheAsp GlnThrAla SerGlu SerTyrAlaThr AspPhe Ala Arg LeuA1aGlu IleG1yArg AspGly ValLeuAlaLeu LeuSer Asp Ser AlaAsnAla AspSerAsn IleGln ValAlaSerGlu SerG1u Val Arg AspGluIle ThrGlnThr IleAla AspTrpGluGly ArgTle Ile Val AlaAlaVal SerSerAsn LeuSer ArgIleGlnGln Ile.Phe Asp 4$ 225 230 235 240 Ala AlaAspLys ThrGlyArg ArgIle ValLeuThrGly PheAsp I1e Glu AsnIleVa1 ArgThrAla IleArg LeuLysLysLeu SerLeu Ala Asn GluIleLeu LeuIleLys Pro.Lys AspMetSerArg PheGlu Asp His GluLeuIle IleLeuGlu ThrGly ArgMetGlyGlu ProIle Asn Gly LeuArg LysMetSer IleGlyArg HisArgTyr ValGluI1e Lys Asp GlyAsp LeuValTyr IleAlaThr AlaProSer IleAlaLys Glu ~

Ala PheVal AlaArgVal GluAsnMet Ile'TyrGln AlaGlyGly Val Val LysLeu IleThrGln SerLeuHis ValSerGly HisGlyAsn Val Arg AspLeu GlriLeuMet IleAsnLeu LeuG1nPro LysTyrLeu Phe Pro ValGln GlyGluTyr ArgGluLeu AspAlaHis AlaLysAla Ala Met AlaVal GlyMetLeu ProGluArg I1ePheIle ProLysLys Gly 405 4l0 415 Thr ThrMet AlaTyrGlu AsnG1yAsp PheValPro AlaGlySer Val ~S

Ser AlaGly AspIleLeu IleAspGly AsnAlaI1e GlyAspVal Gly Asn ValVal LeuArgAsp ArgLysVal LeuSerGlu AspGlyIle Phe Ile Val AlaIleThr ValAsnArgArg GluLys LysIleValAla Arg 35 Ala Arg ValHisThr ArgGlyPheVal TyrLeu LysLysSerArg Asp Ile Leu ArgGluSer SerGluLeuIle AsnGln ThrValGluAsp Tyr Leu Gln GlyAspAsp PheAspTrpAla AspLeu LysGlyLysVal Arg Asp Asn LeuThrLys TyrLeuPheAsp GlnThr LysArgArgPro .Ala Ile Leu ProValVal MetGluAlaLys 545 . 550 <210> 131 <211> 316 <212> PRT
<213> Streptococcus pneumoniae <400> 131 Met Thr Lys Glu Phe His His Val Thr Val Leu Leu His Glu Thr Ile Asp MetLeuAsp ValLysPro AspGlyIle TyrValAsp AlaThrLeu '. Gly GlyAlaGly HisSerGlw TyrLeuLeu SerLysLeu SerGluLys ~

Gly HisLeuTyr AlaPheAsp GlnAspGln AsnAlaTle AspAsnAla Gln LysArgLeu AlaProTyr IleGluLys GlyValVal ThrPheIle 65 70 75 g0 IS Lys AspAsnPhe ArgHisLeu GlnAlaArg LeuArgGlu AlaGlyVal Gln GluTleAsp GlyIleCys TyrAspLeu GlyValSex SerProGln Leu AspGlnArg GluArgGly PheSerTyr LysLysAsp AlaProLeu . MetArgMet AsnGlnAsp AlaSerLeu ThrAlaTyr GluValVal Asp Asn HisTyrAsp TyrHisAsp LeuValArg IlePhePhe LysTyrGly ~

145 150 155 , 160 Glu AspLysPhe SerLysGln IleAlaArg LysIleGlu GlnAlaArg Glu ValLysPro IleGluThr ThrThrGlu LeuAlaGlu IleIleLys 180 l85 190 Leu ValLysPro AlaLysGlu LeuLysLys LysGlyHis ProA1aLys Gln IlePheG1n AlaIleArg IleGluVal AsnAspGlu LeuGlyAla Ala AspGluSer IleGlnGln AlaMetAsp MetLeuAla LeuAspGly Arg IleSerVal IleThrPhe HisSerLeu GluAspArg LeuThrLys Gln LeuPheLys GluAlaSer ThrValGlu ValProLys GlyLeuPro Phe IleProAsp AspLeuLys ProLysMet GluLeuVal SerArgLys Pro IleLeuPro SerAlaGlu GluLeuGlu AlaAsnAsn ArgSerHis Ser AlaLysLeu ArgValVal ArgLysIle HisLys <210> 132 <211> 332 <212> PRT
<213> Streptococcus pneumoniae <400> 132 Met Ser Arg Ile Leu Asp Asn Glu Ile Met Gly Asp Glu Glu Leu Val Glu Arg Thr Leu Arg Pro Gln Tyr Leu Arg Glu Tyr Ile Gly Gln Asp Lys Val Lys Asp Gln Leu Gln Ile Phe Ile Glu Ala Ala Lys Met Arg Asp Glu Ala Leu Asp His Val Leu Leu Phe Gly Pro Pro Gly Leu Gly 50 ~ 55 60 Lys Thr Thr Met Ala Phe Val Ile Ala Asn Glu Leu Gly Val Asn Leu Lys Gln Thr Ser Gly Pro Val Ile Glu Lys Ala Gly Asp Leu Val Ala Ile Leu Asn Glu Leu Glu Pro G1y Asp Val Leu Phe Ile Asp Glu Ile l00 105 110 His Arg Leu Pro Met Ser Val Glu Glu Val Leu Tyr Ser Ala Met Glu Asp Phe Tyr Ile Asp Ile Met Ile Gly Ala Gly Glu Gly Ser Arg Ser 3S 130 ' 135 140 Val His Leu Glu Leu Pro Pro Phe Thr Leu Ile Gly Ala Thr Thr Arg Ala Gly Met Leu Ser Asn Pro Leu Arg Ala Arg Phe Gly Ile Thr Gly His Met Glu Tyr Tyr Ala His Ala Asp Leu Thr Glu Ile Val Glu Arg Thr~Ala Asp Ile Phe Glu Met Glu Ile Thr His Glu Ala Ala Ser Glu Leu Ala Leu Arg Ser Arg Gly Thr Pro Arg Ile Ala Asn Arg Leu Leu Lys Arg Val Arg Asp Phe Ala Gln Ile Met Gly Asn Gly Val Ile Asp 5$ Asp Ile Ile Thr Asp Lys Ala Leu Thr Met Leu Asp Val Asp His Glu 245 250 ~ 255 Gly Leu Asp Tyr Val Asp Gln Lys I1e Leu Arg Thr Met Ile Glu Met Tyr Ser Gly Gly Pro Val Gly Leu Gly Thr Leu Ser Val Asn Ile Ala Glu Glu Arg Glu Thr Val G1u Asp Met Tyr Glu Pro Tyr Leu Ile G1n Lys Gly Phe Ile Met Arg Thr Arg Ser Gly Arg Val Ala Thr Ala Lys 305 310 3l5 320 Ala Tyr Glu His Leu Gly Tyr Glu Tyr Ser Glu Lys <210> 133 <211> 436 <212> PRT
<213> Streptococcus pneumoniae <400> 133 Met Ser Met Phe Leu Asp Thr Ala Lys Ile Lys Val Lys Ala Gly Asn 1 5 , 10 15 Gly Gly Asp G1y Met Val Ala Phe Arg Arg Glu Lys Tyr Val Pro Asn Gly Gly Pro Trp Gly Gly Asp Gly Gly Arg Gly Gly Asn Val Val Phe Val Val Asp Glu Gly Leu Arg Thr Leu Met Asp Phe Arg Tyr Asn Arg His Phe Lys Ala Asp Ser Gly Glu Lys G1y Met Thr Lys Gly Met His .65 70 75 80 Gly Arg Gly Ala Glu Asp Leu Arg Val Arg Val Ser Gln Gly Thr Thr Val Arg Asp Ala Glu Thr Gly Lys Val Leu Thr Asp Leu Ile Lys His Gly Gln Glu Phe Ile Val A1a His Gly Gly Arg Gly Gly Arg Gly Asn Ile Arg Phe Ala Thr Pro Lys Asn Pro Ala Pro Glu Ile Ser Glu Asn Gly Glu Pro Gly Gln Glu Arg Ghu Leu Gln Leu Glu Leu Lys Ile Leu Ala Asp Val Gly Leu Val Gly Phe Pro Ser Val Gly_Lys Ser Thr Leu Leu Ser Val Ile Thr Ser Ala Lys Pro Lys Ile Gly Ala Tyr His Phe Thr Thr Ile Val Pro~Asn Leu Gly Met Val Arg Thr Gln Ser Gly Glu Ser Phe Ala Va1 Ala Asp Leu Pro Gly Leu Ile Glu Gly Ala Ser Gln 210 ' 215 220 Gly Val Gly Leu Gly Thr Gln Phe Leu Arg His Ile Glu Arg Thr Arg Val Ile Leu His Ile Ile Asp Met Ser Ala Ser Glu Gly Arg Asp Pro Tyr Glu Asp Tyr Leu Ala Ile Asn Lys Glu Leu Glu Ser Tyr Asn Leu Arg Leu Met Glu Arg Pro Gln Ile Tle Val Ala Asn Lys Met Asp Met Pro Glu Ser Gln Glu Asn Leu Glu Glu Phe Lys Lys Lys Leu Ala Glu Asn Tyr Asp Glu Phe Glu Glu Leu Pro,Ala Ile Phe Pro Ile Ser Gly Leu Thr Lys Glri Gly Leu Ala Thr Leu Leu Asp Ala Thr Ala Glu Leu Leu Asp Lys Thr Pro Glu Phe Leu Leu Tyr Asp Glu Ser Asp Met Glu 340 ~ 345 350 Glu G1u Ala Tyr Tyr Gly Phe Asp Glu Glu Glu Lys Ala Phe Glu Ile Ser Arg Asp Asp Asp Ala Thr Trp Val.Leu Ser Gly Glu Lys Leu Met Lys Leu Phe Asn Met Thr Asn Phe Asp Arg Asp Glu Ser Val Met Lys Phe Ala Arg Gln Leu Arg Gly Met Gly Val Asp Glu Ala Leu Arg A1a 405 410 4l5 Arg Gly Ala Lys Asp Gly Asp Leu Val Arg Ile Gly Lys Phe Glu Phe . .420 425 430 Glu Phe Val Asp <210> 134 <211> 172 <212> PRT
<213> Streptococcus pneumoniae <400> 134 Met Asn Tyr Phe.Asn Val Gly Lys Ile Val Asn Thr Gln Gly Leu Gln Gly GluMet ArgValLeu SerValThr AspPheAla GluGluArg Phe S

Lys LysGly AlaGluLeu AlaLeuPhe AspGluLys AspGlnPhe Val Gln ThrVal ThrIleAla SerHisArg LysGlnLys AsnPheAsp Ile Ile LysPhe LysAspMet TyrHisIle AsnThrIle GluLysTyr Lys 1S Gly TyrSer LeuLysVal AlaGluGlu AspLeuAsn AspLeuAsp Asp Gly GluPhe TyrTyrHis GluIleIle GlyLeuGlu ValTyrGlu Gly Asp SerLeu ValGlyThr IleLysGlu IleLeuGln ProGlyAla Asn Asp ValTrp ValValLys ArgLysGly LysArgAsp LeuLeuLeu Pro Tyr IlePro ProValVal LeuAsnVal AspIlePro AsnLysArg Val Asp ValGlu IleLeuGlu GlyLeuAsp AspGluAsp <210> 135 <211> 239 <212> PRT

<213> Streptococcus pneumoniae <400> 135 4~ Met Lys AspIleLeu ThrLeuPhe ProGluMet PheSerPro Leu Ile Glu His IleValGly LysAlaArg GluLysGly LeuLeuAsp Ile Ser Gln Tyr AsnPheArg GluAsnAla GluLysAla ArgHisVal Asp His Asp Glu TyrGlyGly GlyGlnGly MetLeuLeu ArgAlaGln Pro Pro Ile Phe SerPheAsp AlaIleGlu LysLysAsn ProArgVal Ile Asp 55 Leu Leu ProAlaGly LysGlnPhe AspGlnAla TyrAlaGlu Asp Asp Leu Ala Gln Glu Glu Glu Leu Ile Phe Ile Cys Gly His Tyr G1u G1y Tyr AspGluArg IleLysThr LeuValThr AspGluIle SerLeuGly Asp TyrValLeu ThrGlyGly GluLeuAla AlaMetThr MetIleAsp 10Ala ThrValArg LeuTlePro GluValIle GlyLysGlu SerSerHis Gln AspAspSer .PheSerSer GlyLeuLeu GluTyrHis GlnTyrThr IS

Arg ProTyrAsp TyrArgGly MetValVal ProAspVal LeuMetSer Gly HisHisGlu LysIleArg GlnTrpArg LeuTyrGlu SerLeuLys Lys ThrTyrGlu ArgArgPro AspLeuLeu GluHisTyr GlnLeuThr 25Val GluGluGlu LysMetLeu AlaGluTle LysGluAsn LysGlu <210> 136 <21l> l86 <212> PRT
3S <213> Streptococcus pneumoniae <400> 136 Met Ile Glu Ala Ser Lys Leu Lys Ala Gly Met Thr Phe Glu Thr Ala Asp Gly Lys Leu Ile Arg Val Leu Glu Ala Ser His His Lys Pro Gly 4$Lys Gly Thr IleMetArg MetLysLeu ArgAspVal ArgThrGly Asn Ser ThrPheAsp ThrSerTyr ArgProGlu GluLysPhe GluGlnAla Ile IleGluThr ValProAla GlnTyrLeu TyrLysMet AspAspThr Ala TyrPheMet AsnThrGlu ThrTyrAsp GlnTyrGlu IleProVal Val Asn Val Glu Asn Glu Leu Leu Tyr Ile Leu Glu Asn Ser Asp Val 100 l05 110 Lys Ile Gln'Phe TyrGlyThr GluValIle GlyValThr ValProThr 115 _ 120 125 Thr Val GluLeu ThrValAla GluThrGln ProSerIle LysGlyAla Thr Val ThrGly SerGlyLys ProAlaThr MetGluThr GlyLeuVal Val Asn ValPro AspPheIle GluAlaGly GlnLysLeu ValIleAsn 165' 170 175 1$Thr Ala GluGly ThrTyrVal SerArgAla l80 185 <210> 137 <21l>

<212>
PRT

<213> pneumoniae Streptococcus ~5 <400>

Met AlaPheGlu SerLeuThr GluArgLeu GlnAsnVal PheLysAsn Leu ArgLysLys GlyLysIle SerGluSer AspValGln GluA1aThr 3~ 20 25 30 Lys GluIleArg LeuAlaLeu LeuGluAla AspValAla LeuProVal 35 40 45 ' .

35 Val LysAspPhe IleLysLys ValArgGlu ArgAlaVal GlyHisGlu Val IleAspThr LeuAsnPro AlaGlnGln IleIleLys IleValAsp Glu GluLeuThr AlaValLeu GlySerAsp ThrAlaGlu IleIleLys 85 90 ~ 95 Ser ProLysIle ProThrIle IleMetMet ValGlyLeu GlnGlyAla Gly LysThrThr PheAlaGly LysLeuAla AsnLysLeu LysLysGlu 50 Glu AsnAlaArg ProLeuMet IleAlaAla AspIleTyr ArgProAla Ala IleAspGln LeuLysThr LeuGlyGln GlnIleAsp ValProVal 145 150 155~ 160 Phe AlaLeuGly ThrGluVal ProAlaVal GluIleVal ArgGlnGly Leu G1u G1n Ala Gln Thr Asn His Asn Asp Tyr Val Leu Ile Asp Thr S Ala Gly Arg Leu Gln Ile Asp Glu Leu Leu Met Asn Glu Leu Arg Asp Val Lys Thr Leu Ala Gln Pro Asn Glu Ile Leu Leu Val Val Asp Ala Met Ile Gly Gln Glu Ala Ala Asn Val Ala Arg Glu Phe Asn Ala Gln Leu Glu Val Thr Gly Val Ile Leu Thr Lys Ile Asp Gly.Asp Thr Arg G1y Gly Ala Ala Leu Ser Val Arg His Ile Thr Gly Lys Pro Ile Lys Phe Thr Gly Thr Gly Glu Lys Ile Thr Asp Ile Glu Thr Phe His Pro Asp Arg Met Ser Sex Arg Ile Leu Gly Met Gly Asp Met Leu Thr Leu Ile Glu Lys Ala Ser Gln Glu ,Tyr Asp Glu Gln Lys Ala Leu Glu Met A1a Glu Lys Met Arg Glu Asn Thr Phe Asp Phe Asn Asp Phe Ile Asp Gln Leu Asp Gln Val Gln Asn Met Gly Pro Met Glu Asp Leu Leu Lys Met Ile Pro Gly Met Ala Asn Asn Pro Ala Leu Gln Asn Met Lys Val Asp Glu Arg Gln Ile Ala Arg Lys Arg Ala Ile Val Ser Ser Met Thr Pro Glu Glu Arg Glu Asn Pro Asp Leu Leu Asn Pro Ser Arg Arg Arg Arg Ile Ala Ala Gly Ser Gly Asn Thr Phe Val Glu Val Asn Lys Phe Ile Lys Asp Phe Asn Gln Ala Lys Gln Leu Met Gln Gly Val Met Ser 5~ Gly Asp Met Asn Lys Met Met Lys Gln Met Gly Ile Asn Pro Asn Asn Leu Pro Lys Asn Met Pro Asn Met Gly Gly Met Asp Met Ser Ala Leu Glu Gly Met Met Gly Gln Gly Gly Met Pro Asp Leu Ser Ala Leu Gly Gly Ala Gly Met Pro Asp Met Ser Gln Met Phe Gly Gly Gly Leu Lys S Gly Lys Ile Gly Glu Phe Ala Met Lys Gln Ser Met Lys Arg Met Ala Asn Lys Met Lys Lys Ala Lys Lys Lys Arg Lys 1~
<210>

<211>

<212>
PRT

IS <213> pneumoniae Streptococcus <400>

Met TyrLeuIle GluIleLeu LysSerIle PhePheGly IleValGlu 1 5 10 ' 15 Gly IleThrGlu TrpLeuPro IleSerSer ThrGlyHis LeuIleLeu Ala GluGluPhe IleGlnTyr GlnAsnGln AsnGluAla PheMetSer Met PheAsnVal ValIleGln LeuGlyAla IleLeuAla ValMetVal ~

3~ Ile TyrPheAsn LysLeuAsn,ProPheLys Pro~ThrLys AspLysGln Glu ValArgLys ThrTrpArg LeuTrpLeu LysValLeu IleAlaThr Leu ProLeuLeu GlyValPhe LysPheAsp AspTrpPhe AspThrHis Phe HisAsnMet ValSerVal AlaLeuMet LeuIleIle TyrGlyVal 0 ' 115 120 125 Ala PheIleTyr LeuGluLys ArgAsnLys AlaArgAla IleGluPro 45 Ser ValThrGlu LeuAspLys LeuProTyr ThrThrAla PheTyrIle Gly LeuPheGln ValLeuAla LeuLeuPro GlyThrSer ArgSerGly $~ .

Ala ThrIleVal GlyGlyLeu LeuAsnGly ThrSerArg SerValVal Thr GluPheThr PheTyrLeu GlyIlePro ValMetPhe GlyAlaSer Ala LeuLysIle PheLysPhe ValLysAla GlyGluLeu LeuSerPhe Gly Gln Leu Phe Leu Leu Leu Val Ala Met G1y Val Ala Phe Ala Val Ser Met Val Ala Ile Arg Phe Leu Thr Ser Tyr Val Lys Lys His Asp Phe Thr Leu Phe Gly Lys Tyr Arg Ile Val Leu Gly Ser Val Leu Leu Leu Tyr Ser Phe Val Arg Leu Phe Val IS
<210> 139 <211> 429 <212> PRT
<213> Streptococcus pneumoniae <400> 139 Met Gly Leu Phe Asp Arg Leu Phe Gly Lys Lys Glu Glu Pro Lys Ile 2S Glu Glu Val Val Lys Glu Ala Leu Glu Asn Leu Asp Leu Ser Glu Asp Ile Glu Pro Ala Phe Thr Glu Ala Glu Glu Val Ser Gln Glu Glu Ala Glu Val Glu Ser Ser Glu Glu Ser Val Phe Gln Glu Glu Asp Ser Gln Asp Thr Val Glu Glu Asn Leu Asp Leu Glu Pro Val Val Glu Val Ser Gln Glu Glu Val Glu Glu Phe Pro Asn Ser Gln Glu Val Thr Glu Glu Glu Lys Leu Glu His Glu Gly Thr Val Glu Glu Asn Asn Phe Glu Val Leu Glu Pro Glu Ala Pro G1n Thr Glu Glu Thr Val Gln Glu Lys Tyr Asp Arg Ser Leu Lys Lys Thr Arg Thr Gly Phe Gly Ala Arg Leu~Asn A1a Phe Phe Ala Asn Phe Arg Ser Val Asp Glu Glu Phe-Phe Glu Glu Leu Glu Glu Leu Leu Ile Met Ser Asp Val Gly Val Gln Val Ala Ser Asn Leu Thr Glu Glu Leu Arg Tyr Glu Ala Lys Leu Glu Asn Ala Lys Lys Pro Asp Ala Leu Arg Arg Val Ile Ile Glu Lys Leu Val Glu Leu Tyr Glu Lys Asp Gly Sex Tyr Asp Glu Ser Ile His Phe Gln Asp Asn Leu Thr Val Met Leu, Phe Val Gly Val Asn Gly Val Gly Lys Thr Thr Ser Ile Gly Lys Leu Ala His Arg Tyr Lys Arg Ala Gly Lys Lys Val Met Leu Val Ala Ala Asp Thr Phe Arg Ala Gly Ala Val Ala Gln Leu Ala Glu Trp Gly Arg Arg Val Asp Val Pro Val Val Thr Gly Pro Glu 275 ~ 280 285 Lys Ala Asp Pro Ala Ser Val Val Phe Asp Gly Met Glu Arg Ala Val Ala Glu Gly Ile Asp Ile Leu Met Ile Asp Thr Ala Gly Arg Leu Gln Asn Lys Asp Asn Leu Met Ala Glu Leu Glu Lys Ile Gly Arg Ile Ile Lys Arg Val Val Pro Glu Ala Pro,His Glu Thr Phe Leu Ala Leu Asp Ala Ser Thr Gly Gln Asn Ala Leu Val Gln Ala Lys Glu Phe Ser Lys Ile Thr Pro Leu Thr G1y Ile Val Leu Thr Lys Ile Asp Gly Thr Ala Arg Gly Gly Val Val Leu Ala Ile Arg Glu Glu Leu Asn Ile Pro Val 385 . 390 395 400 Lys Leu Ile Gly Phe Gly Glu Lys Ile Asp Asp Ile Gly Glu Phe Asn 405 410 ' 415 Ser Glu Asn Phe Met Lys Gly Leu Leu Glu Gly Leu Ile <210> 140 <211> 165 <212> PRT
<213> Streptococcus pneumoniae <400> 140 Met Tyr Ile Glu Met Val Asp Glu Thr Gly Gln Val Ser Lys Glu Met Leu Gln Gln Thr Gln Glu Ile Leu Glu Phe Ala Ala Lys Lys Leu Gly 20 . 25 30 Lys Glu Asp Lys Glu Met Ala Val Thr Phe Val fihr Asn Glu Arg Ser His Glu Leu Asn Leu Glu Tyr Arg Asp Thr Asp Arg Pro Thr Asp Val Ile SerLeuGlu TyrLysPro GluLeuGlu IleAlaPhe AspG1uGlu Asp LeuLeuG1u AsnProGlu LeuAlaGlu MetMetSer GluPheAsp Ala TyrIleG1y GluLeuPhe IleSerIle AspLys.AlaHisGluGln Ala GluGluTyr GlyHisSer PheGluArg GluMetGly PheLeuAla 2~ Val HisGlyPhe LeuHisIle AsnGlyTyr AspHisTyr ThrProGlu Glu GluAlaGlu MetPheGly LeuGlnGlu G1uIleLeu ThrAlaTyr Gly LeuThrArg Gln <210> 141 <211>

<212>
PRT

<213> pneumoniae Streptococcus 35<400>

Met SerIleArg ValIleIle AlaGlyPhe LysGlyLys MetGlyGln 1 5 l0 15 Ala AlaCysGln MetValLeu ThrAspPro AspLeuAsp LeuValAla Val LeuAspPro PheGluSer GluSerGlu TrpGlnGly IleProVa1 35 ' 40 45 45Phe LysAspLys AlaAspLeu AlaGlyPhe GluAlaAsp ValTrpVal Asp PheThrThr ProAlaVal AlaTyrGlu AsnThrArg PheAlaLeu Glu AsnGlyPhe AlaProVal ValGlyThr ThrGlyPhe ThrSerGlu Glu IleAlaGlu LeuLysGlu PheSerArg AlaGlnAsp LeuGlyGly Leu IleAlaPro AsnPheAla LeuGlyAla ValLeuLeu MetGlnPhe Ala ThrGlnAla AlaLys TyrPheProAsn ValGluIle IleGluLeu S

His HisAspLys LysLys AspAlaProSer GlyThrAla IleLysThr Ala GluLeuMet AlaGlu ValArgGluSer IleGlnGln GlyAlaA1a Asp GluGluGlu LeuTle AlaGlyAlaArg GlyAlaAsp PheAspGly IS Met ArgIleHis SerVal ArgLeuProG1y LeuValAla HisGlnGlu Val IlePheGly AsnGln GlyGluGlyLeu ThrLeuArg HisAspSer Tyr AspArgIle SerPhe MetThrGlyVal AsnLeuGly IleLysGlu Val ValLysArg HisGlu LeuValTyrGly LeuGluHis LeuLeu <210>

<211>

<212>
PRT

<213> pneumoniae Streptococcus <400>

Met AlaAsnLys GlnAsp LeuTleAla.Lys ValAlaGlu AlaThrGlu 3S 1 5 10 l5 Leu ThrLysLys AspSer AlaAlaAlaVal GluAlaVal PheAlaAla 20 ~ 25 30 Val AlaAspTyr LeuAla AlaGlyGluLys ValGlnLeu IleGlyPhe Ser AsnPheGlu ValArg-GluArgAlaG1u ArgLysGly ArgAsnPro ~

Gln ThrGlyLys GluMet ThrIle,AlaAla SerLysVal ProAlaPhe Lys Ala Gly Lys Ala Leu Lys Asp Ala Val Lys <210> 143 <211> 306 SS <212> PRT
<213> Streptococcus pneumoniae 81 .

<400> 143 Met Thr Lys Thr Ala Phe Leu Phe Ala Gly Gln Gly Ala Gln Tyr Leu Gly Met Gly Arg Asp Phe Tyr Asp Gln Tyr Pro Ile Val Lys Glu Thr Ile Asp Arg Ala Ser Gln Val Leu Gly Tyr Asp Leu Arg Tyr Leu Ile Asp Thr Glu Glu Asp Lys Leu Asn Gln Thr Arg Tyr Thr Gln Pro Ala Ile Leu Ala Thr Ser Val Ala Ile Tyr Arg Leu Leu Gln Glu Lys Gly Tyr Gln Pro Asp Met Val Ala Gly Leu Ser Leu Gly Glu Tyr Ser Ala Leu Val Ala Ser Gly Ala Leu Asp Phe Glu Asp Ala Val Ala Leu Val Ala Lys Arg Gly Ala Tyr Met Glu Glu Ala Ala Pro Ala Asp Ser Gly 115 l20 125 Lys Met Val Ala Val Leu Asn Thr Pro Val Glu Val Ile Glu Glu, Ala Cys Gln,Lys Ala Ser Glu Leu Gly Val Val Thr Pro Ala Asn Tyr Asn 145 ' 150 155 160 Thr Pro Ala Gln Ile Val Ile Ala Gly Glu Val Val Ala~Val Asp Arg Ala Val Glu Leu Leu Gln Glu Ala Gly Ala Lys Arg Leu Ile Pro Leu Lys Val Ser Gly Pro Phe His Thr Ala Leu Leu Glu Pro Ala Ser Gln .
Lys Leu Ala Glu Thr Leu Ala Gln Val Ser Phe Ser Asp Phe Thr Cys 210 ~ 215 220 Pro Leu Val Gly Asn Thr Glu Ala Ala Val Met Gln Lys Glu Asp Ile Ala Gln Leu Leu Thr Arg Gln Val Lys Glu Pro Val Arg Phe Tyr Glu Ser Ile Gly Val Met Gln Glu Ala Gly Ile Ser Asn Phe Ile Glu Ile Gly Pro Gly Lys Val Leu Ser Gly Phe Val Lys Lys Ile Asp Gln Thr Ala His Leu Ala His Val Glu Asp Gln Ala Ser Leu Val Ala Leu Leu Glu Lys <210>

<211>

<212>
PRT

<213> pneumoniae Streptococcus <400>

Met LysLeu .GluHisLys AsnIlePhe IleThrGly SerSerArg Gly Ile GlyLeu AlaIleAla HisLysPhe AlaGlnAla GlyAlaAsn Ile Val LeuAsn SerArgGly AlaIleSer GluGluLeu LeuAlaGlu Phe Ser AsnTyr GlyIleLys ValVa1Pro IleSerGly AspValSer Asp Phe AlaAsp AlaLysArg MetIleAsp GlnAlaIle AlaGluLeu Gly 25'65 70 75 80 Ser ValAsp ValLeuVal AsnAsnAla GlyIleThr GlnAspThr Leu Met LeuLys MetThrGlu.AlaAspPhe GluLysVal LeuLysVal Asn Leu ThrGly AlaPheAsn MetThrGln SerValLeu LysProMet Met Lys AlaArg GluGlyAla IleIleAsn MetSerSer ValValGly Leu Met GlyAsn IleGlyGln AlaAsnTyr AlaAlaSer LysAlaGly Leu Ile GlyPhe ThrLysSer ValAlaArg GluValAla SerArgAsn Ile Arg ValAsn ValIleAla ProG1yMet IleGluSer AspMetThr Ala Ile LeuSer AspLysIle LysGluAla ThrLeuAla GlnIlePro Met Lys GluPhe GlyGlnAla GluGlnVal AlaAspLeu ThrValPhe Leu Ala GlyGln AspTyrLeu ThrGlyG1n ValValAla IleAspGly Gly Leu Ser Met <210>

<21 1> 76 <21 2>
PRT

<21 3> treptococcus pneumoniae S

<40 0> 45 Met GlyValLys LysLys LeuLysLeu ThrSerLeuLeu GlyLeu Ser 1 5 . 10 15 Leu LeuIleMet ThrAla CysAlaThr AsnGlyValThr SerAsp Ile Thr AlaG1uSer AlaAsp PheTrpSer LysLeuValTyr PhePhe Ala 3 4'0 4 Glu IleIleArg PheLeu SerPheAsp Ile.SerIleGly ValGly Ile 50 55 60 , Ile LeuPheThr ValLeu IleArgThr ValLeuLeuPro ValPhe Gln Val GlnMetVal AlaSer ArgLysMet GlnGluAlaG1n ProArg Tle Lys AlaLeuArg GluGln TyrProGly ArgAspMetGlu SerArg Thr Lys LeuGluGln GluMet ArgLysVal PheLysGluMet G1yVal Arg Gln SerAspSer LeuTrp ProIleLeu IleGlnMetPro Va1Ile Leu 3$ 130 135 140 Ala LeuPheGln AlaLeu SerArgVal AspPheLeuLys ThrGly His Phe LeuTrpIle AsnLeu GlySerVal AspThrThrLeu ValLeu Pro 165~ 170 175 Ile LeuAlaAla ValPhe ThrPheLeu SerThrTrpLeu SerAsn Lys 180 185 . 190 .

Ala LeuSerGlu ArgAsn GlyAlaThr ThrAlaMetMet TyrGly Ile Pro ValLeuIle PheIle PheAlaVal TyrAlaProGly GlyVal Ala Leu TyrTrpThr ValSer AsnAlaTyr GlnValLeuGln ThrTyr Phe Leu AsnAsnPro PheLys IleIleAla GluArgGluAla ValVa1 Gln Ala Gln Lys Asp Leu Glu Asn Arg Lys Arg Lys Ala Lys Lys Lys Ala Gln Lys Thr Lys <210> 146 <211> 409 <212> PRT
<213> Streptococcus pneumoniae <400> 146 Met Lys Ile Ser Lys Arg His Leu Leu Asn Tyr Ser Ile Leu Ile Pro Tyr Leu Leu Leu Ser Ile Leu Gly Leu Ile Val Val Tyr Ser Thr Thr 20 Ser Ala Ile Leu Ile Glu Glu Gly Lys Ser Ala Leu Gln Leu Va1 Arg 35 40 ' 45 Asn GlnGly IlePheTrp IleValSerLeu TleLeuIle AlaLeuIle Tyr LysLeu ArgLeuAsp PheLeuArgAsn GluArgLeu IleIleLeu Val IleLeu IleGluMet LeuLeuLeuPhe LeuAlaArg PheIleGly ' 85 90 95 Ile SerVal AsnGlyAla TyrGlyTrpIle SerValAla GlyValThr I1e GlnPro AlaGluTyr LeuLysIleIle IleIleTrp TyrLeuAla 115 120 125 .

His ArgPhe SerLysGln GlnGluGluIle AlaThrTyr AspPheGln Val LeuThr GlnAsnGln TrpLeuProArg AlaPheAsn AspTrpArg Phe ValLeu LeuValLeu IleGlySerLeu GlyIlePhe ProAspLeu Gly AsnAla ThrIleLeu ValLeuValSer LeuIleMet TyrThrVal Ser GlyIle AlaTyrArg TrpPheSerThr IleLeuAla LeuValSer Ala ThrSer ValPheVal LeuThrThrIle SerLeuIle GlyValGlu 210 215 . 220 Thr PheSer LysTlePro ValPheGlyTyr ValAlaLys ArgPheSer Ala Phe Phe Asn Pro Phe Ala Asp Arg Ala Asp Ala Gly His Gln Leu Ala Asn SerTyr PheAlaMet ValAsnGly GlyTrpPhe GlyLeuGly Leu Gly AsnSer IleGluLys ArgGlyTyr LeuProGlu AlaHisThr ~

Asp Phe ValPhe SerIleVal IleGluGlu PheGlyPhe ValGlyAla Ser Leu IleLeu AlaLeuLeu PhePheMet IleLeuArg IleIleLeu 305 310~ 315 320 Val Gly IleArg AlaGluAsn ProPheAsn AlaMetVal AlaLeuGly Val Gly GlyMet MetLeuVal GlnValPhe ValAsnIle GlyGlyIle Ser Gly LeuIle ProSexThr GlyVa1Thr PheProPhe LeuSerGln Gly Gly AsnSer LeuLeuVal LeuSerVal AlaValAla PheValLeu Asn Ile AspAla SerGluLys ArgA1aLys LeuTyrArg GluLeuGlu Asn Gln ProMet AsnLeuLeu LeuLys <210> 147 <211> 419 <212> PRT

<213> Streptococcus pneumoniae <400> 147 Met Leu IleLeu ThrPheIle LeuValPhe G1yIle IleValVal Gly Val His PheGly HisPheTyr PheAlaLys LysSer GlyIleLeu Glu Val Arg PheAla IleGlyMet GlyProLys .IlePhe AlaHisIle Glu Gly Lys GlyThr AlaTyrThr IleArgIle LeuPro LeuGlyGly Asp Tyr Val MetAla GlyTrpGly AspAspThr ThrGlu IleLysThr Arg SS 65 70 75 ' Gly Thr ValSer LeuThrLeu AlaAspAsp GlyLys ValLysArg Pro Ile Asn Leu Ser Gly Lys Lys Leu Asp Gln Thr Ala Leu Pro Met Gln S
Val Thr G1n Phe Asp Phe Glu Asp Lys Leu Phe Ile Lys Gly,Leu Val 115 120 ' 125 Leu Glu Glu Gl,u Lys Thr Phe Ala Val Asp His Asp Ala Thr Val Val l~ 130 135 140 Glu Ala Asp Gly Thr Glu Val Arg Ile Ala Pro Leu Asp Val Gln Tyr 145 150 155 l60 1$ Gln Asn Ala Thr Ile Trp Gly Lys Leu Ile Thr Asn Phe Ala Gly Pro Met Asn Asn Phe Ile Leu Gly Val Val Val Phe Trp Val Leu Ile Phe _ 180 185 190 Met Gln Gly Gly Val Arg Asp Val Asp Thr Asn Gln Phe His Ile Met Pro Gln Gly Ala Leu Ala Lys Val Gly Val Pro Glu Thr Ala Gln Ile Thr Lys Ile Gly Ser His Glu Val Ser Asn Trp Glu Ser Leu Ile Gln 3~ Ala Val Glu Thr Glu Thr Lys Asp Lys Thr.Ala Pro Thr Leu Asp Va1 Thr Ile Ser Glu Lys Gly Ser Asp Lys Gln Val Thr Val Thr Pro Glu Asp Ser Gln Gly Arg Tyr Leu Leu Gly Val Gln Pro Gly Val Lys Ser Asp Phe Leu Ser Met Phe Val Gly Gly Phe Thr Thr Ala Ala Asp Ser Ala Leu Arg Ile Leu Ser Ala Leu Lys Asn Leu Ile Phe Gln Pro Asp Leu Asn Lys Leu Gly Gly Pro Val Ala Ile Phe.Lys Ala Ser Ser Asp Ala Ala Lys Asn Gly Ile Glu Asn Ile Leu Tyr Phe Leu Ala Met Ile Ser Ile Asn Ile Gly Ile Phe Asn.Leu Ile Pro Ile, Pro Ala Leu Asp Gly Gly Lys I1e Val Leu Asn Ile Leu Glu Ala Ile Arg Arg Lys Pro Leu Lys Gln Glu Ile Glu Thr Tyr Val Thr Leu Ala Gly Val Val Ile Met Val Val Leu Met Ile Ala Val Thr Trp Asn Asp Ile Met Arg Leu Phe Phe Arg <210> 148 <211> 197 <212> PRT
<213> Streptococcus pneumoniae IS <400> 148 Met Tyr Ala Tyr Leu Lys Gly Ile I1e Thr Lys Ile Thr Ala Lys Tyr Ile Val Leu Glu Thr Asn Gly Ile Gly Tyr Ile Leu His Val Ala Asn 20 ' 25 30 Pro,Tyr Ala Tyr Ser Gly Gln Val Asn Gln Glu Ala Gln Tle Tyr Val His Gln Val Val Arg Glu Asp Ala His Leu Leu Tyr Gly Phe Arg Ser 50 ,55 60 Glu Asp Glu Lys Lys Leu Phe Leu Ser Leu Ile Ser Val Ser Gly I1e Gly Pro Val Ser A1a Leu Ala Ile Ile Ala Ala Asp Asp Asn Ala Gly 85 90 ~ 95 Leu Val Gln Ala Ile Glu Thr Lys Asn Ile Thr Tyr Leu Thr Lys Phe 100 105 1l0 Pro Lys Ile Gly Lys Lys Thr Ala Gln Gln Met Val Leu Asp Leu Glu Gly Lys Val Val Val Ala Gly Asp Asp Leu Pro Ala Lys Val Ala~Val 130 ~ 135 140 Gln Ala Ser Ala Glu Asn Gln Glu Leu Glu Glu Ala Met Glu Ala Met Leu Ala Leu Gly Tyr Lys Ala Thr Glu Leu Lys Lys Ile Lys Lys Phe Phe Glu Gly Thr Thr Asp Thr Ala Glu Asn Tyr Ile.Lys Ser Ala Leu ~Lys Met Leu Val Lys <210> 149 <211> 257 <212>
PRT

<213> pneumoniae Streptococcus <400>

Met LysAsn AsnArgIle LeuAlaLeu SerGlyAsn AspIlePhe Ser Gly GlyGly LeuSerAla AspLeuAla ThrTyrThr LeuAsnGly Leu His GlyPhe ValAlaVal ThrCysLeu ThrAlaLeu ThrGluLys Gly Phe GluVal PheProThr AspAspThr IlePheGln HisGluLeu Asp Ser LeuArg AspValG1u PheGlyGly IleLysIle GlyLeuLeu Pro Thr Va1Ser ValAlaGlu LysAlaLeu AspPheIle LysGlnArg Pro Gly ValPro ValValLeu AspProVal LeuValCys LysGluThr His Asp ValAla ValSerGlu LeuCysGln GluLeuIle ArgPhePhe Pro Tyr ValSer ValIleThr ProAsnLeu ProGluAla GluLeuLeu Ser Gly GlnGlu TleLysThr LeuGluAsp MetLysThr AlaAlaGln Lys Leu HisAsp LeuGlyAla ProAlaVal IleIleLys GlyGlyAsn Arg Leu SerGln AspLysAla ValAspVal PheTyr.AspG1yGlnThr Phe 180 ~ 185 190 Thr IleLeu GluAsnPro ValIleGln GlyGlnAsn AlaGlyAla Gly Cys ThrPhe AlaSerSer IleAlaSer HisLeuVal LysGlyAsp Lys Phe LeuPro AlaValGlu SerSerLys AlaPheVal TyrArgAla Ile Ala GlnAla AspGlnTyr GlyValArg GlnTyrGlu AlaAsnLys Asn Asn <210> 150 <211> 412 <212> PRT
<213> Streptococcus pneumoniae <400> 150 Met Ile Glu Thr Glu Lys Lys Glu Glu Arg Val Leu Leu Ile Gly Val Glu Leu Gln Gly Met Asp Ser Phe Asp Leu Ser Met Glu Glu Leu Ala Ser Leu Ala Lys Thr Ala Gly Ala Val Val Val Asp Ser Tyr Arg Gln IS Lys Arg Glu Lys Tyr Asp Ser Lys Thr Phe Val Gly Ser Gly Lys Leu Glu G1u Ile Ala Leu Met Val Asp Ala Glu Glu Ile Thr Thr Val Ile Val Asn Asn Arg Leu Thr Pro Arg Gln Asn Val Asn Leu Glu Glu Val Leu Gly Val Lys Val Ile Asp Arg Met Gln Leu Ile Leu Asp Ile Phe 2S 100 l05 110 Ala Met Arg Ala Arg Ser His Glu Gly Lys Leu Gln Val His Leu Ala l15 120 125 Gln Phe Lys Tyr Leu Leu Pro Arg Leu Val Gly Gln Gly Ile Met Leu Ser Arg Gln Ala Gly G1y Ile Gly Ser Arg Gly Pro Gly Glu Ser Gln 145 l50 155 160 Leu Glu Leu Asn Arg Arg Ser Val Arg Asn Gln Ile Thr Asp Tle Glu Arg Gln Leu Lys Val Val Glu Lys Asn Arg Ala Thr Val Arg Glu Lys Arg Leu Glu Ser Ser Thr Phe Lys Ile Gly Leu Ile Gly Tyr Thr Asn Ala Gly Lys Ser Thr Ile Met Asn Ile Leu Thr Ser Lys Thr Gln Tyr Glu Ala Asp Glu Leu Phe Ala Thr Leu Asp A1a Thr Thr Lys Ser Ile 225 230 235 _ 240 His Leu Gly .Gly Asn Leu Gln Val Thr Leu Thr Asp Thr Val Gly Phe Ile Gln Asp Leu Pro Thr Glu Leu Va1 Ser Ser Phe Lys Ser Thr Leu G1u Glu Ser Lys His Val Asp Leu Leu.Val His Val Ile Asp Ala Ser Asn Pro TyrHis GluGluHis GluLysThr ValLeuSer IleMetLys Asp Leu AspMet GluAspIle ProHisLeu ThrLeuTyr AsnLysA1a Asp Leu ValGlu AspPheThr ProThrGln ThrProTyr ThrLeuIle Ser Ala LysSer GluAspSer ArgGluAsn LeuGlnAla LeuLeuLeu ~ISAsp Lys IleLys GluIlePhe GluAlaPhe ThrLeuArg ValProPhe 355 360 , 365 Ser Lys SerTyr LysIleHis AspLeuGlu SerValAla IleLeuGlu 370 . , 375 380 Glu Arg AspTyr GlnGluAsp GlyGluVal IleThrGly TyrIleSer Glu Lys AsnLys TrpArgLeu GluGluPhe TyrAsp <210> 151 <211> 160 <212> PRT

<213> StreptococouS pneumoniae <400> 151 Met Ala Lys ThrTyrPro MetThrLeu GluGluLys GluLysLeu Glu Glu Lys Leu GluGluLeu LysLeuVal ArgArgPro GluValVal Glu Glu Arg Lys TleAlaArg SerTyrGly AspLeuSer GluAsnSer Ile Glu Tyr Ala AlaLysAsp GluGlnAla PheValGlu GlyGlnIle Glu Ser Ser Glu ThrLysIle ArgTyrAla GluIleVal AsnSerAsp Leu 65 70 75 gp Ala Val Gln AspGluVal AlaI1eGly LysThrVal ThrIleGln Ala .

Glu Ile Gly Glu Asp Glu Glu Glu Val Tyr Ile Ile Val Gly Ser Ala 5 Gly Ala Asp Ala Phe Ala Gly Lys Val Ser Asn Glu Ser Pro Ile Gly Gln Ala Leu Ile Gly Lys Lys Thr Gly Asp Thr Ala Thr Ile Glu Thr 13.0 135 140 Pro Val G1y Ser Tyr Asp Val Lys Ile Leu Lys Va1 Glu Lys Thr Ala 145 l50 l55 160 <210>

<211> 89 <212>
PRT

<213> tococcus pneumoniae Strep <400>

Met ThrLysLeu LeuValGly LeuGly AsnProGlyAsp LysTyrPhe 1 5 10 ' 15 Glu ThrLysHis AsnValGly PheMet LeuIleAspGln LeuAlaLys Lys GlnAsnVal ThrPheThr HisAsp LysIlePheGln AlaAspLeu Ala SerPhePhe LeuAsnGly GluLys IleTyrLeuVal LysProThr Thr PheMetAsn GluSerGly LysAla ValHisAlaLeu LeuThrTyr Tyr GlyLeuAsp IleAspAsp LeuLeu TleIleTyrAsp AspLeuAsp Met GluValGly LysIleArg LeuArg .AlaLysGlySer AlaGlyG1y 100 105 , 110 His AsnGlyIle LysSerIle IleGln HisIleGlyThr GlnValPhe Asn ArgValLys IleGIyIle GlyArg ProLysAsnGly MetSerVal Val HisHisVal LeuSerLys PheAsp ArgAspGluTyr IleGlyIle Leu GlnSerVal AspLysVal AspAsp SerValAsnTyr TyrLeuGln $0 G1u LysAsnPhe GluLysThr MetGln ArgTyrAsnGly <210> 153 <211> 283 <212> PRT
<213> Streptococcus pneumoniae <400> 153 Met Ile Leu Tle Thr Gly Ala Asn Gly Gln Leu Gly Thr Glu Leu Arg Tyr Leu Leu Asp Glu Arg Asn Glu Glu Tyr Val_ Ala Val Asp Val Ala Lys Met Asp Ile Thr Asn Glu.Glu Met Val Glu Lys Val Phe Glu Glu Val Lys Pro Thr Leu Val Tyr His Cys Ala Ala Tyr Thr Ala Val Asp IS Ala Ala Glu Asp Glu Gly Lys Glu Leu Asp Phe Ala-Ile Asn Val Thr 65 70 75 g0 Gly Thr Lys Asn Val Ala Lys Ala Ser Glu Lys His Gly Ala Thr Leu Val Tyr Ile Ser Thr Asp Tyr Val Phe Asp Gly Lys Lys Pro Val Gly Gln Glu Trp Glu Val Asp Asp Arg Pro Asp Pro Gln Thr Glu Tyr Gly 2$ 115 120 125 Arg Thr Lys Arg Met Gly Glu Glu Leu Val Glu Lys His Val Ser Asn Phe Tyr Ile Ile Arg Thr Ala Trp Val Phe Gly Asn Tyr Gly Lys Asn Phe Val Phe Thr Met Gln Asn Leu Ala Lys Thr His Lys Thr Leu Thr 165 ~ 170 175 Val Val Asn Asp Gln Tyr Gly Arg Pro Thr Trp Thr Arg Thr Leu Ala Glu Phe Met Thr Tyr Leu Ala Glu Asn Arg Lys Glu Phe Gly Tyr Tyr 0 195 ~ 200 205 His Leu Ser Asn Asp Ala Thr Glu Asp Thr Thr Trp Tyr Asp Phe Ala $ Val GlwIle Leu Lys Asp Thr Asp Val Glu Val Lys~Pro Va1 Asp Ser Ser Gln Phe Pro Ala Lys Ala Lys Arg Pro Leu Asn Ser Thr Met Ser Leu Ala Lys Ala Lys Ala Thr Gly Phe Val Ile Pro Thr Trp Gln Asp Ala Leu Gln Glu Phe Tyr Lys Gln Glu Val Arg .275 280 <210>

<211> 07 S <212>
PRT

<213> treptococcus pneumoniae S

<400> 54 Met LysArgSer LeuAspSer ArgValAsp TyrSerLeu LeuLeuPro Val PhePheLeu LeuValTle GlyValVal AlaIleTyr IleAlaVal 1$ Ser HisAspTyr ProAsnAsn IleLeuPro IleLeuGly GlnGlnVal Ala TrpIleAla LeuGlyLeu ValIleGly PheValVal MetLeuPhe Asn ThrGluPhe LeuTrpLys ValThrPro PheLeuTyr IleLeuGly 65 70 75 $0 Leu GlyLeuMet IleLeuPro Ile~ValPhe TyrAsnPro SerLeuVa1 Ala SerThrGly AlaLysAsn TrpValSer IleAsnGly IleThrLeu 100 l05 110 Phe GlnProSer GluPheMet LysIleSer TyrIleLeu MetLeuAla Arg ValIleVal GlnPheThr LysLysHis LysGluTrp ArgArgThr 130 l35 140 Val ProLeuAsp PheheuLeu IlePheTrp MetTleLeu PheThrIle Pro ValLeuVal LeuLeuAla LeuGlnSer AspLeuGly ThrAlaLeu Val PheValAla IlePheSer GlyIleVal LeuLeuSer GlyValSer 5 Trp LysIleIle IleProVal PheValThr AlaValThr GlyValAla Gly PheLeuAla IlePheIle SerLysAsp GlyArgAla PheLeuHis 50 .

Gln IleGlyMet ProThrTyr GlnIleAsn ArgIleLeu AlaTrpLeu Asn ProPheGlu PheAlaGln ThrThrThr TyrGlnGln AlaGlnGly Gln IleAlaIle GlySerGly GlyLeuPhe.GlyGlnGly PheAsnAla Ser Asn Leu Leu Ile Pro Val Arg Glu Ser Asp Met Ile Phe Thr Val Ile Ala Glu Asp Phe Gly Phe Ile Gly Ser Val Leu Val Ile Ala Leu Tyr Leu Met Leu Ile Tyr Arg Met Leu Lys Ile Thr Leu Lys Ser Asn 305 310 3l5 320 Asn Gln Tyr ThrTyr IleSerThr GlyLeuIle MetMetLeu Leu Phe IS Phe His Phe GluAsn IleGlyAla ValThrGly LeuLeuPro Leu Ile Thr Gly Pro LeuPro PheTleSer GlnGlyGly SerAlaIle Ile Ile Ser Asn Tle GlyVal GlyLeuLeu LeuSerMet SerTyrGln Thr Leu Asn Leu Glu GluLys SerGlyLys ValProPhe LysArgLys Lys Ala Val Val Lys GlnIle Lys Leu <210> 155 <211> 202 <212> PRT

<213> Streptococcus pneumoniae' <400> 155 Met Gly Ile IleGly IleThrGly GlyIleAla SerGlyLys Ser Lys 1 . 5 10 15 Thr Val Asn PheLeu LysHisGln GlyLeuSer SerSerGly Leu Thr 20 ' 25 30 Pro Thr,Gln Cys Ser Thr Asn Tyr Arg Lys Pro. Gly Gly Arg Leu Phe Glu Ala LeuVal GlnHisPhe GlyGlnGlu IleIleLeu GluAsnGly 55 .

Glu Leu AsnArg ProLeuIle AlaSerLeu IlePheSer-AsnProGlu Glu Gln LysTrp SerAsnGln IleGlnGly GluTleIle ArgGluGlu . 90 95 55Leu Ala ThrLeu ArgGluGln LeuAlaGln ThrGluGlu IlePhePhe Met Asp Ile Pro Leu Leu Phe Glu Gln Asp Tyr Ser Asp Trp Phe Ala 115 120 ~. 125 Glu Thr Trp Leu Va1 Tyr Val Asp Arg Asp Ala Gln Val Glu Arg Leu $ 130 135 140 Met Lys Arg Asp Gln Leu Ser Lys Asp Glu Ala Glu Ser Arg Met Ala Ala Gln Trp Pro Leu~Glu Lys Lys Lys Asp Leu Ala Ser Gln Val Leu Asp Asn Asn Gly Asn Gln Asn Gln Leu Leu Asn Gln Val His Ile Leu Leu Glu Gly Gly Arg Gln Asp Asp Arg Asp <210> 156 <211> 419 <212> PRT
<213> Streptococcus pneumoniae 2S <400> 156 Met Arg Lys Tle Val Ile Asn Gly Gly Leu Pro Leu Gln Gly Glu Ile Thr Ile Ser Gly Ala Lys Asn Ser Val Val Ala Leu I1e Pro Ala Ile 20 ~ 25 30 Ile Leu Ala Asp Asp Va~l Val Thr Leu Asp Cys Val Pro Asp Ile Ser 3$ Asp Val Ala Ser Leu Val Glu Ile Met Glu Leu Met Gly Ala Thr Val Lys ArgTyrAsp AspValLeu GluIleAsp ProArgGly'ValGlnAsn Ile ProMetPro TyrGlyLys IleAsnSer LeuArgAla SerTyrTyr Phe TyrGlySer LeuLeuGly ArgPheGly GluAlaThr ValGlyLeu Pro GlyGlyCys AspLeuGly ProArgPro IleAspLeu HisLeuLys $0Ala PheGluAla MetGlyAla ThrAlaSer TyrGluGly AspAsnMet Lys LeuSerAla LysAspThr GlyLeuHis GlyAlaSer IleTyrMet SS

Asp ThrValSer ValGlyAla ThrIleAsn ThrMetIle AlaAlaVal Lys AlaAsn Gly Thr IleIleGlu AlaAlaArg GluPro Glu Arg Asn Ile IleAsp ValAlaThr LeuLeuAsn AsnMetGlyAla HisIle Arg Gly AlaGly ThrAsnIle IleIleIle AspGlyValGlu ArgLeu His Gly ThrArg HisGlnVa1 IleProAsp ArgIleGluAla GlyThr Tyr Ile SerLeu AlaAlaAla ValGlyLys GlyIleArgIle AsnAsn Val Leu TyrGlu HisLeuGlu GlyPheIle AlaLysLeuGlu GluMet Gly Val ArgMet ThrValSer GluAspSer IlePheValGlu GluGln Ser Asn LeuLys AlaIleAsn IleLysThr AlaProTyrPro GlyPhe Ala Thr AspLeu G1nGlnPro LeuThrPro LeuLeuLeuArg AlaAsn Gly Arg GlyThr IleValAsp ThrIleTyr GluLysArgVal AsnHis Val Phe GluLeu AlaLysMet AspAlaAsp IleSerThrThr AsnGly His 3S Ile LeuTyr ThrGlyGly ArgAspLeu ArgGlyAlaSer ValLys Ala Thr AspLeu ArgAlaGly AlaAlaLeu ValIleAlaGly LeuMet Ala Glu GlyLys ThrGluIle ThrAsnIle GluPheIleLeu ArgGly Tyr Ser AspIle IleGluLys LeuArgAsn LeuGlyAlaAsp IleArg Leu Val Glu Asp <210> 157 <211> 231 <212> PRT
<213> Streptococcus pneumoniae <400> 157 Met Ser Arg Ile Glu Phe Ser Pro Ser Leu Met Thr Met Asp Leu Asp 1 5 10 l5 Lys PheLys GluGlnIle Thr~PheLeuAsnAsp LysValAlaSer Tyr His TleAsp IleMetAsp GlyHis PheValPro AsnIleThrLeu Ser 35 4.0 45 Pro TrpPhe IleGlnGlu ValGln LysIleSer AspThrProLeu Ser Val HisLeu MetValThr AspPro ThrPheTrp ValAspGlnVal Leu IS Asp LeuGln CysGluTyr IleCys IleHisAla GluValLeuAsn Gly Leu AlaPhe ArgLeuIle AspLys IleHisAsp AlaGlyLeuLys Ala Gly ValVal LeuAsnPro GluThr ProValSer ThrIle.PhePro Tyr 21e AspLeu LeuAspLys ValThr IleMetThr ValAspProGly Phe Ala GlyGln ArgPheLeu GluSer ThrLeuTyr LysIleGlnGlu Leu Arg GlnLeu ArgValGln AsnGly TyrHisTyr IleTleGluMet Asp Gly SerSer SerArgLys ThrPhe LysGlnIle AspValAlaGly Pro Asp IleTyr ValIleGly ArgSer GlyLeuPhe GlyLeuAspAsp Asp Ile AlaLys AlaTrpAsp IleCys SerArgAsp TyrGluGluMet Thr Gly LysThr MetProIle Lys <210> 158 <211> 37,4 <212> PRT
<213> Streptococcus pneumoniae .
<400> 158 Met Arg Asn Met Ala Leu Thr Ala G1y 21e Val Gly Leu Pro Asn Val 1 5 10 ~ 15 SS Gly Lys Ser Thr Leu Phe Asn Ala Ile Thr Lys Ala Gly Ala Glu Ala Ala AsnTyr ProPheAla ThrIleAsp ProAsnVal GlyMetVal Glu Asp ProAsp GluArgLeu GlnLysLeu ThrGluMet IleThrPro Lys Lys ThrVal ProThrThr PheGluPhe ThrAspIle AlaGlyIle Val Lys GlyAla SerLysGly GluGlyLeu GlyAsnLys PheLeuAla Asn Ile ArgG1u ValAspAla IleValHis ValValArg AlaPheAsp Asp Glu AsnVal MetArgGlu GlnGlyArg GluAspAla PheValAsp Pro Leu AlaAsp IleAspThr IleAsnLeu GluLeuIle LeuAlaAsp Leu Glu SerVal AsnLysArg TyrAlaArg ValGluLys MetAlaArg Thr 2$ Gln LysAsp LysGluSer ValAlaGlu PheAsnVal LeuGlnLys Ile Lys ProVal LeuG1uAsp GlyLysSer AlaArgThr IleGluPhe Thr Asp GluGlu GlnLysVal ValLysGly LeuPheLeu LeuThrThr Lys Pro ValLeu TyrValAla AsnValAsp GluAspVal ValSerGlu Pro Asp SerIle AspTyrVal LysGlnIle ArgGluPhe AlaAlaThr Glu 225 230 , 235 240 40 Asn AlaGlu ValValVal IleSerAla ArgAlaGlu GluGluIle Sex Glu LeuAsp AspGluAsp LysLysGlu PheLeuGlu AlaIleGly Leu Thr GluSer GlyValAsp LysLeuThr ArgAlaAla .TyrHisLeu Leu Gly LeuGly ThrTyrPhe ThrAlaGly GluLysGlu ValArgAla Trp Thr PheLys ArgGlyMet LysAlaPro GlnAlaAla GlyIleIle His 55 Ser AspPhe GluLysGly PheIleArg AlaValThr MetSerTyr Glu Asp Leu Val Lys Tyr Gly Ser Glu Lys Ala Val Lys Glu Ala Gly Arg Leu Arg Glu Glu Gly Lys Glu Tyr Ile Val Gln Asp Gly'Asp Ile Met Glu Phe Arg Phe Asn Val <210> 159 <211> 110 _ <212> PRT
<213> Streptococcus pneumoniae <400> 159 Met Glu Ile Glu Lys Thr Asn Arg Met Asn Ala Leu Phe Glu Phe Tyr Ala Ala Leu Leu Thr Asp Lys Gln Met Asn Tyr Ile Glu Leu Tyr Tyr Ala Asp TyrSerLeu AlaGluIle AlaGluGlu PheGlyVal Ser Asp 35 ~ 40 45 Arg Gln ValTyrAsp AsnIleLys ArgThrGlu LysIleLeu Glu Ala Asp Tyr MetLysLeu HisMetTyr SerAspTyr IleValArg Ser Glu Gln Ile AspGlnIle LeuGluArg TyrProLys AspAspPhe Leu Phe Gln Glu IleGluIle LeuThrSer IleAspAsn ArgG1u Gln <210> 160 <211> 223 <212> PRT

<213> Streptococcus pneumoniae <400> 160 Met Thr GluTrpGlu GluPheLeu AspProTyr IleGlnAla Val Leu Gly Glu LysIleLys LeuArgGly IleArgLys GlnTyrArg Lys Leu 20 25 ~ ~ 30 Gln Asn HisSerPro IleGluPhe ValThrGly ArgValLys Pro Lys Ile Glu IleLysGlu LysMetAla ArgArgGly IleThrTyr Ala Ser 50 . 55 60 Thr Leu HisAspLeu GlnAspIle AlaGlyLeu ArgValMet Val Glu Gln PheValAsp AspValLys GluValVal AspIleLeu HisLysArg Gln AspMetArg IleIleGln GluArgAsp TyrIleThr HisArgLys Ala SerGlyTyr ArgSerTyr HisValVal ValGluTyr ThrValAsp Thr IleAsnGly AlaLysThr IleLeuAla GluIleGln IleArgThr 1$ Leu AlaMetAsn PheTrpAla ThrIleG1u HisSerLeu AsnTyrLys Tyr GlnGlyAsp PheProAsp GluTleLys LysArgLeu GluIleThr 165. 170 175 Ala ArgIleAla HisGlnLeu AspGluGlu MetGlyGlu IleArgAsp Asp IleGlnGlu AlaGln,AlaLeuPheAsp ProLeuSer ArgLysLeu Asn AspGlyVal GlyAsnSer AspAspThr AspGluGlu TyrArg <210> 161 <211> 195 <212> PRT.

<213> Streptococcus pneumoniae <400> 161 Met Glu Asn ThrHisAsn AlaGluIle LeuLeuSer AlaAlaAsn Leu 40.Lys Ser Tyr ProGlnAsp GluLeuPro GluIleAla LeuAlaGly His Arg Ser Val GlyLysSer SerPheIle AsnThrMet LeuAsnArg Asn Lys Asn Ala ArgThrSer GlyLysPro GlyLysThr GlnLeuLeu Leu Asn Phe Asn IleAspAsp LysMetArg PheValAsp ValProGly Phe Tyr Gly A1a ArgValSer LysLysGlu ArgGluLys TrpGlyCys Tyr Met I1e Glu TyrLeuThr ThrArgGlu AsnLeuArg AlaValVal Glu ~

. 100 105 110 Ser LeuVal AspLeu HisAsp ProSerAla AspAspVal GlnMet Arg Tyr GluPhe LeuLys TyrGlu IleProVal IleIleVal AlaThr Tyr Lys AlaAsp LysIle ArgGly LysTrpAsn LysHisGlu SerAla Pro Ile LysLys LysLeu PheAsp ProSerAsp AspPheIle LeuPhe Asn Ser SerVal SerLys GlyMet AspGluAla TrpAspAla IleLeu Ala Glu Lys Leu <210> 162 <211> 97 <212> PRT
<213> Streptococcus pneumoniae .
2S <400> 162 Met Lys Thr Arg Lys Ile Pro Leu Arg Lys Ser Val Val Ser Asn Glu Val Ile Asp Lys Arg Asp Leu Leu Arg Ile Val Lys Asn Lys Glu Gly Gln Val Phe Ile Asp Pro Thr Gly Lys Ala Asn Gly Arg G1y Ala Tyr 35 Ile Lys Leu Asp Asn Ala Glu A1a Leu Glu Ala Lys Lys Lys Lys Val Phe Asn Arg Ser Phe Ser Met Glu Val Glu Glu Ser Phe Tyr Asp Glu Leu Ile Ala Tyr Val Asp His Lys Val Lys Arg Arg Glu Leu Gly Leu Glu J3 <210> 163 <211> l03 $0 <212> PRT
<213> Streptococcus pheumoniae <400:~.''i163 Met Leu Lys Pro Ser Ile Asp Thr Leu Leu Asp Lys Val Pro Ser Lys 55 1 5 l0 15 Tyr Ser Leu Val Ile Leu Glu Ala Lys Arg A1a His Glu Leu Glu Ala 20 25- 3'0 Gly Ala Pro Ala Thr Gln Gly Phe Lys Ser Glu Lys Ser Thr Leu Arg S
I~la Leu Glu Glu I1e Glu Ser Gly Asn Val Thr Ile His Pro Asp Pro Glu Gly Lys Arg Glu Ala Val Arg Arg~Arg Ile Glu Glu Glu Lys Arg Arg Lys Glu Glu Glu Glu Lys Lys Ile Lys Glu Gln Ile Ala Lys Glu IS Lys Glu Asp Gly Glu Lys Ile <210> 164 <211> 103 <2l2> PRT
<213> Streptococcus pneumoniae <400> 164 Met Ser Leu Thr Ser Lys Gln Arg Ala Phe Leu Asn Ser Gln Ala His Thr Leu Lys Pro Ile I1e Gln Ile Gly Lys Asn Gly Leu Asn Asp Gln Ile Lys Thr Ser Val Arg Gln Ala Leu Asp Ala Arg Glu Leu Ile Lys Val Thr Leu Leu Gln Asn Thr Asp Glw Asn Tle His Glu Val Ala Glu 35 50 55 . 60 Ile Leu Glu Glu Glu Ile Gly Val Asp Thr Val Gln Lys Tle G1y Arg Ile Leu Ile Leu Phe Lys Gln Ser Ser Lys Lys Glu Asn Arg Lys Ile Ser Lys Lys Val Lys Glu Ile <210> 165 <211> 175 <212> PRT
<213> Streptococcus pneumoniae <400> 165 Met Ala Ile Glu Asn Tyr Tle Pro Asp Phe Ala Val Glu Ala Val Tyr 1 5 10 l5 Asp .Leu Thr Val Pro Ser Leu Gln Ala Gln Gly Ile Lys Ala Val Leu Va1 AspLeuAsp AsnThr LeuIleAla TrpAsnAsn ProAspGlyThr Pro GluMetLys GlnTrp LeuHisAsp LeuArgAsp AlaGlyIleGly Ile IleValVal SerAsn AsnThrLys Lys,ArgVal GlnArgAlaVal Glu LysPheGly IleAsp TyrValTyr TrpAlaLeu LysProPheThr Phe GlyIleAsp ArgAla MetLysGlu PheHisTyr AspLysLysGlu Val ValMetVal GlyAsp GlnLeuMet ThrAspIle ArgAlaAlaHis Arg AlaGlyIle ArgSer IleLeuVal LysProLeu ValGlnHisAsp 13.0 135 140 Ser IleLysThr GlnIle AsnArgThr ArgGluArg ArgValMetArg 7.45 150 155 160 Lys IleThrGlu LysTyr GlyProIle ThrTyrLys LysGlyIle 1210> 166 <211> 455 <212> PRT

<213> Streptococcus pneumoniae <400> 166 Met Phe Lys I1eLeuIle AlaAsn ArgGlyGluIle AlaValArg Arg Ile Ile Ala AlaArgGlu LeuGly IleAlaThrVal AlaValTyr Arg Ser Thr Asp LysGluAla LeuHis ThrLeuLeuAla AspGluAla Ala Val Cys Gly ProGlyLys AlaThr GluSerTyrLeu AsnIleAsn Ile Ala Val Ser AlaAlaVal LeuThr GluAlaGluAla IleHisPro Leu Gly Phe Phe LeuSerGlu AsnSer LysPheAlaThr MetCysGlu Gly Glu Ile Gly Ile Lys Phe Ile Gly Pro Ser Gly His Val Met Asp Met Met Gly Asp Lys Ile Asn Ala Arg Ala Gln Met Ile Lys Ala Gly Val Pro Val Ile Pro Gly Ser Asp Gly Glu Val His Asn Ser Glu Glu Ala 130 135 140.
Leu Ile Val Ala Glu Lys Ile Gly Tyr Pro Val Met Leu Lys Ala Ser Ala Gly Gly Gly Gly Lys Gly Ile Arg Lys Val Glu Lys Pro Asp Asp Leu Val Ser Ala Phe Glu Thr Ala Ser Ser Glu Ala Lys Ala Asn Tyr 1$ Gly Asn Gly Ala Met Tyr Ile Glu Arg Val Ile Tyr Pro Ala Arg His Ile Glu Val Gln Ile Leu Gly Asp Glu His Gly His Val Ile His Leu ' Gly Glu Arg Asp Cys Ser Leu Gln Arg Asn Asn G1n Lys Val Leu Glu 225 230 ' 235 ' 240 Glu Ser Pro Ser Ile Ala Ile Gly Lys Thr Leu Arg His Glu Ile Gly ~Ala Ala Ala Val Arg Ala Ala Glu Phe Val Gly Tyr Glu Asn Ala Gly Thr Ile Glu Phe Leu Leu Asp Glu Ala Ser Ser Asn Phe Tyr Phe Met 275 280 . 285 Glu Met Asn Thr Arg Val Gln Val Glu His Pro Val Thr Glu Phe Val Ser Gly Val Asp Ile Val Lys Glu Gln Ile Cys Ile Ala Ala Gly Gln Pro Leu Ser Val Lys Gln Glu Asp Ile Val Leu Arg Gly His Ala Ile Glu Cys Arg Ile Asn Ala Glu Asn Pro Ala Phe Asn Phe Ala Pro Ser Pro Gly Lys Ile Thr Asn Leu Tyr Leu Pro Ser Gly Gly Val Gly Leu Arg Val Asp Ser Ala Val Tyr Pro Gly Tyr Thr Ile Pro Pro Tyr Tyr Asp Ser Met Ile Ala Lys Ile Ile Val His Gly Glu Asn Arg Phe Asp Ala Leu Met Lys Met Gln Arg Ala Leu Tyr Glu Leu Glu Ile Glu Gly Val~Gln Thr Asn Ala Asp Phe Gln Leu Asp Leu Ile Ser Asp Arg Asn Val Ile Ala Gly Asp Tyr Asp Thr Cys Phe Leu Met Glu Thr Phe Leu Pro Lys Tyr Gln Glu Lys Glu <210> 167 <211> 77 <212> PRT
<213> Streptococcus pneumoniae <400> 167 Met Ile Tyr Lys Val Phe Tyr Gln Glu Thr Lys Glu Arg Ser Pro Arg Arg Glu Thr Thr Arg Ala Leu Tyr Leu Asp Ile Asp Thr Ser Ser Glu Leu GluGly Ile Thr ArgGln Leu GluGlu Asn Arg Arg Ala Val Pro Glu TyrAsn Glu Tyr GluLeu Leu AspLys Leu Leu Ile Ile Ser Asp Tyr GluLys Thr Gly PheGlu Ile GluPhe Glu Ala Thr 65 ~ 70 75 <210> 168 <211> 336 <212> PRT

<213> Streptococcus pneumoniae <400> 168 Met Lys ArgTyrIle Leu Phe GluThr Ser AspGlu Asp Ala Cys Thr 1 . ~ 10 15 Ser Val ValLeuL'ys Asn Asp GluLeu Leu AsnVal Ala Asp Ser Ile Ala Ser IleGluSer His Arg PheGly Gly ValPro Gln Lys Val Glu Val Ala Ser Arg His His Val Glu Val Ile Thr Ala Cys Ile Glu Glu 50 Ala Leu Ala Glu Ala Gly Ile Thr Glu Glu Asp Val Thr Ala Val A1a Val Thr Tyr Gly Pro Gly Leu Val Gly Ala Leu Leu Val Gly Leu Ser Ala Ala Lys Ala Phe Ala Trp Ala His Gly Leu Pro Leu Ile Pro Val Asn HisMetAla GlyHis LeuMetAla AlaGlnSerVal GluPro Leu Glu PheProLeu LeuAla LeuLeuVal SerGlyGlyHis ThrGlu Leu Val TyrValSer GluAla GlyAspTyr LysIleValGly GluThr Arg 145 , 150 155 , 160 Asp AspAlaVal GlyGlu AlaTyrAsp LysValGlyArg ValMet Gly Leu ThrTyrPro AlaGly ArgGluIle AspGluLeuAla HisGln Gly Gln AspIleTyr AspPhe ProArgAla MetIleLysGlu AspAsn Leu Glu PheSerPhe SerGly LeuLysSer AlaPheIleAsn LeuHis His Asn AlaGluGln LysGly GluSer-LeuSerThrGluAsp LeuCys Ala Ser PheGlnAla AlaVal MetAspIle 'LeuMetAlaLys ThrLys Lys A1a LeuGluGlu TyrPro ValLysThr LeuPheValAla GlyGly Val Ala AlaAsnLys GlyLeu ArgGluArg LeuAlaAlaGlu IleThr Asp 3$ Val LysValTle IlePro ProLeuArg LeuCysG1yAsp AsnAla Gly ~

Met IleAlaTyr AlaSer ValSerGlu Trp,AsnLysGlu AsnPhe Ala Gly TrpAspLeu Asn.Ala LysProSer LeuAlaPheAsp ThrMet Glu <210> 169 <2l1> 602 $0 <212> PRT
<213> Streptococcus pneumoniae <400> 169 Met Cys Gly Ile Val Gly Val Val Gly Asn Thr Asn Ala Thr Asp Ile SS_ 1 5 , 10 15 veu Ile Gln Gly Leu Glu Lys Leu Glu Tyr Arg Gly Tyr Asp Ser Ala Gly Ile Phe Val Leu Asp Gly Ala Asp Asn His Leu Val Lys Ala Val Gly Arg Ile Ala Glu Leu Ser Ala Lys Thr Ala Gly Val Glu Gly Thr Thr Gly Ile Gly His Thr Arg Trp Ala Thr His Gly Lys Pro Thr Glu Asp Asn Ala His Pro His Arg Ser Glu Thr Glu Arg Phe Val Leu Val His Asn Gly Val Ile Glu Asn Tyr Leu Glu Ile Lys Glu Glu Tyr Leu A1a Gly His His Phe Lys Gly Gln Thr Asp Thr Glu Ile Ala Val His Leu Ile Gly Lys Phe Ala Glu Glu Glu Gly Leu Ser Val Leu Glu Ala l30 135 140 Phe Lys Lys Ala Leu His Ile Ile Arg Gly Ser Tyr Ala Phe Ala Leu I1e Asp Ser Glu Asn.Pro Asp Val Ile Tyr Val Ala Lys Asn Lys Ser 165 ' 170 175 Pro Leu Leu Ile Gly Leu Gly Glu Gly Tyr Asn Met Val Cys Ser Asp Ala Met Ala Met Ile Arg Glu Thr Asn Gln Tyr Met Glu Ile His Asp Gln Glu Leu Val Ile Val Lys Ala Asp'Ser Val Glu Val Gln Asp Tyr Asp Gly Asn Ser Arg Glu Arg Ala Ser Tyr Thr Ala Glu Leu Asp Leu 225 230 235 240.
Ser Asp Ile Gly Lys Gly Thr Tyr ProITyr Tyr Met Leu Lys Glu Ile Asp Glu Gln Pro Thr Val Met Arg Lys Leu Ile Gln Ala Tyr Thr Asp Asp Ala Gly Gln Val Val Val Ala Pro Ala Ile Ile Lys Ala Val Gln Asp Ala Asp Arg Ile Tyr Ile Leu Ala Ala Gly Thr Sex Tyr His Ala Gly Phe Ala Ser Lys Lys Met Leu Glu Glu Leu Thr Asp Thr Pro Val Glu Leu Gly Ile Ser Ser Glu Trp Gly Tyr Gly Met Pro Leu Leu Ser Lys LysProLeu PheIlePhe IleSerGln SerGlyGlu ThrAla Asp Ser ArgGlnVal LeuValLys AlaAsnGlu MetGlyIle ProSer Leu Thr ValThrAsn ValProGly SerThrLeu SerArgGlu AlaAsn Tyr l~ 370 375 380 Thr MetLeuLeu HisAlaGly ProGluIle AlaValAla SerThr Lys 15Ala TyrThrAla GlnIleAla AlaLeuAla PheLeuAla LysAla Val Gly GluAlaAsn GlyAsnAla LysAlaGln AlaPheAsp LeuVal His Glu LeuSerIle ValAlaGln SerIleGlu SerThrLeu SerGlu Lys Glu ThrIleGlu AlaLysVal ArgGluLeu LeuGluThr ThrArg Asn Ala PheTyrIle GlyArgGly GlnAspTyr TyrValAla MetGlu Ala 30.Ser LeuLysLeu LysGluIle SerTyrIle GlnCysGlu GlyPhe Ala Ala GlyGluLeu LysHisGly ThrIleAla LeuIleGlu GluGly Thr Pro ValLeuAla LeuLeuSer AspProVal LeuAlaAsn HisThr Arg Gly AsnIleGln GluValAla AlaArgGly AlaLysVal LeuThr I1e Ala GluGluAsn ValAlaLys AspThrAsp AspIleVal LeuThr Thr 545 550' 555 560 Val HisProTyr LeuSerPro IleSerMet ValValPro ThrGln Leu 565 570 ~ 575 Val AlaTyrPhe AlaThrLeu HisArgGly LeuAspVal AspLys Pro 580 58,5 590 Arg AsnLeuAla LysSerVal ThrValGlu SS <210> 170 <211> 240 <212> PRT

<213> Streptococcus pneumoniae <400> 170 Met Ile Arg Ile Glu Asn Leu Ser Val Ser Tyr Lys Glu Thr Leu Ala $ 1 5 10 15 Zeu Lys Asp Ile Ser Leu Val Leu His Gly Pro Thr Ile Thr Gly Tle Ile Gly Pro Asn Gly Ala Gly Lys Ser Thr Leu Leu Lys Gly Met Leu Gly Ile Ile Pro His Gln Gly Gln Ala Phe Leu Asp Asp Lys Glu Val Lys Lys Ser Leu His Arg Ile Ala Tyr Val Glu Gln Lys Ile Asn Ile Asp Tyr Asn Phe Pro Ile Lys Val Lys Glu Cys Val Ser Leu Gly Leu Phe ProSerIle ProLeu PheArgSer LeuLysAlaLys HisTrp Lys Lys ValGlnGlu AlaLeu GluTleVal GlyLeuAlaAsp TyrAla Glu Arg GlnIleSer GlnLeu SerGlyGly GlnPheGlnArg ValZeu Ile Ala ArgCysLeu ValGln GluAlaAsp TyrIleLeuLeu AspGlu Pro Phe AlaGlyI1e AspSer ValSerG1u GluIleIleMet AsnThr Leu Arg AspLeuLys LysAla GlyLysThr ValLeuIleVal HisHis Asp Leu SerLysIle ProHis TyrPheAsp GlnValLeuLeu ValAsn Arg Glu ValIleAla PheGly ProThrLys GluThrPheThr GluThr Asn 2l0 215 220 Leu LysGluAla TyrGly AsnG1nLeu PhePheAsnGly GlyAsp Leu <210> 171 , <211> 740 5$ <212> PRT
<213> Streptococcus pneumoniae <400> 171 Met Pro Lys Glu Val Asn Leu Thr Gly Glu Glu Val Val Ala Leu Thr Lys Glu Tyr Leu Thr Glu Glu Asp Val His Phe Val His Lys Ala Leu Val Tyr Ala Val Glu Cys His Ser Gly Gln Tyr Arg Lys Ser Gly Glu Pro Tyr Ile Ile His Pro Ile Gln Val Ala Gly Ile Leu Ala Lys Leu Lys Leu Asp Ala Val Thr Val Ala Cys Gly Phe Leu His Asp Val Val Glu Asp Thr Asp Ala Thr Leu Asp Asp Leu Glu Arg Glu Phe Gly Pro Asp Val Arg Val Ile Val Asp Gly Val Thr Lys Leu Gly Lys Val Glu l00 105 110 Tyr Lys Ser Ile Glu Glu Gln Leu Ala Glu Asn His Arg Lys Met Leu Met Ala Met Ser Glu Asp.Ile Arg Val Ile Leu Val Lys Leu Ser Asp Arg Leu His Asn Met Arg Thr Leu Lys His Leu Arg Lys Asp Lys Gln Glu Arg Ile Ser Lys Glu Thr Met Glu Ile Tyr Ala Pro Leu Ala His Arg Leu Gly Ile Ser Ser Val Lys Trp Glu Leu Glu Asp Leu Ser Phe Arg Tyr Leu Asn Pro Thr Glu Phe Tyr Lys Ile Thr His Met Met Lys Glu Lys Arg Arg Glu Arg Glu Ala Leu Val Asp Glu Val Val Thr Lys Leu Glu Glu Tyr Thr Thr Glu Arg His Leu Lys Gly.Lys Ile Tyr Gly Arg Pro Lys His Ile Tyr Ser Ile Phe Arg Lys Met Gln Asp Lys Arg Lys Arg Phe Glu Glu Ile Tyr Asp Leu Ile Ala Ile Arg Cys Ile Leu Asp Thr Gln Ser Asp Val Tyr Ala Met Leu Gly Tyr Val His Glu Phe Trp Lys Pro Met Pro Gly Arg Phe Lys Asp Tyr Ile Ala Asn Arg Lys Ala AsnGly TyrGlnSer IleHisThr ThrValTyr GlyProLys Gly Pro IleGlu PheGlnIle ArgThrLys GluMetHis GluValAla Glu Tyr GlyVal AlaAlaHis TrpAlaTyr LysLysGly IleLysGly Gln Val AsnSer LysGluSer AlaIleGly MetAsnTrp IleLysG1u Met Met GluLeu GlnAspGln AlaAspAsp A1aLys,GluPheValAsp Ser Val LysGlu AsnTyrLeu AlaGluGlu IleTyrVal PheThrPro Asp Gly Ala.Val ArgSerLeu ProLysAsp SerGlyPro IleAspPhe Ala Tyr GluIle HisThrLys ValGlyGlu LysAlaThr GlyAlaLys Val Asn GlyArg MetValPro LeuThrThr LysLeuLys ThrGlyAsp Gln Val GluIle IleAlaAsn ProAsnSer PheGlyPro SerArgAsp Trp Leu Asn Met Val Lys Thr Ser Lys Ala Arg Asn Lys Ile Arg Gln Phe 465 470 ~ 475 480 Phe Lys Asn Gln Asp Lys Glu Leu Ser Val Asn Lys Gly Arg Glu Met Leu MetAla GlnPheGln GluAsnGlyTyr ValAlaAsn LysPhe Met Asp LysArg HisMetAsp GlnValLeuGln LysThrSer TyrLys Thr , Glu AspSer LeuPheA1a AlaIleGlyPhe GlyGluIle GlyAla Ile Thr ValPhe AsnArgLeu ThrGluLysGlu ArgArgGlu GluGlu Arg 545 , 550 555 560 Ala LysAla LysAlaGlu AlaGluGluLeu ValLysGly GlyGlu Val Lys ValGlu AsnLysGlu ThrLeuLysVal LysHisGlu GlyGly Val Val IleGlu GlyAlaSer GlyLeuLeuVal ArgIleAla LysCys Cys Asn ProValPro GlyAsp AspIleValGly TyrIle ThrLysGly Arg S Gly ValAlaIle HisArg ValAspCysMet AsnLeu ArgAlaGlnGlu 625 .630 635 640 Asn TyrGluGln ArgLeu LeuAspValGlu TrpGlu AspGlnTyrSer Ser SerAsnLys GluTyr LeuA1aHisIle AspIle TyrGlyLeuAsn Arg ThrG1yLeu LeuAsn AspValLeuGln ValLeu SerAsnThrThr Lys AsnIleSer ThrVal AsnAlaGlnPro ThrLys AspMetLysPhe Ala AsnIleHis ValSer PheGlyIleAla AsnLeu SerThrLeuThr Thr ValValAsp LysTle LysSerValPro GluVal TyrSerValLys Arg Thr Asn Gly <210> 172 <211> 492 <212> PRT

<213> Streptococcus pneumoniae 35<400> 172 Met Ser .TrpAspThrLys PheLeuLys LysGlyPhe ThrPheAsp Asn Asp Val Leu IleProAla GluSerHis ValLeuPro AsnAspAla Leu Asp Leu Thr LysLeuAla AspAsnLeu ThrLeuAsn IleProIle Thr 45Ile Thr Ala MetAspThr ValThrGlu SerG1nMet AlaIleAla Ala Ile Ala Ala GlyGlyLeu GlyValIle HisLysAsn MetSerTle Arg Ala Gln Ala AspGluVal~~ArgLysVal LysArgSer GluAsnGly Gln Val Tle Ile Asp Pro Phe Phe Leu Thr Pro Glu His Thr Ile Ala Glu Ala Asp Glu Leu Met Gly Arg Tyr Arg Ile Ser Gly Val Pro Val Val Glu ThrLeu GluAsnArg LysLeuVal GlyIleLeu ThrAsnArg Asp Leu ArgPhe IleSerAsp TyrAsnGln ProIleSer AsnHisMet Thr Ser GluAsn LeuValThr AlaProVal GlyThrAsp LeuAlaThr Ala Glu SerIle LeuGlnGlu HisArgIle .GluLysLeu ProLeuVal Asp IS Glu GluGly SerLeuSer GlyLeuIle ThrIleLys AspI1eGlu Lys Val IleGlu PheProAsn AlaAlaLys AspGluPhe GlyArgLeu Leu Val AlaGly AlaValGly ValThrSer AspThrPhe G1uArgAla Glu Ala LeuPhe GluAlaG1y AlaAspAla IleValIle AspThrAla His Gly HisSer AlaGlyVal LeuArgLys IleAlaGlu IleArgAla His Phe ProAsp ArgThrLeu IleAlaGly AsnIleAla ThrAlaGlu Gly Ala ArgAla LeuTyrGlu AlaGlyVal AspValVal LysValGly Ile G1'yProGly SerIleCys ThrThrArg ValIleAla GlyValGly Val Pro GlnVal ThrAlaIle TyrAspAla AlaAlaVal AlaArgGlu Tyr Gly LysThr IleIleAla AspGlyGly IleLysTyr SerGlyAsp Ile Val LysAla LeuAlaAla GlyGlyAsn AlaValMet LeuGlySer Met Phe AlaGly ThrAspGlu AlaProGly GluThrGlu IlePheGln Gly Arg LysPhe LysThrTyr ArgGlyMet GlySerIle AlaAlaMet Lys -Lys GlySer SerAspArg TyrPheGln GlySerVal AsnGluAla Asn Lys LeuVal ProGluGly IleGluGly ArgValAla TyrLysGly Ala Ala Ala Asp Ile Val Phe Gln Met Ile Gly Gly Lle Arg Ser Gly Met Gly Tyr Cys Gly Ala Ala Asn Leu Lys Glu Leu His Asp Asn Ala Gln Phe Ile Glu Met Ser Gly Ala Gly Leu Lys Glu Ser His Pro His Asp Val Gln Tle Thr Asn Glu Ala Pro Asn Tyr Ser Met <210> 173 <211> 648 <212> PRT
<213> Streptococcus pneumoniae <400> 173 Met Thr Glu Glu Ile Lys Asn Leu Gln Ala Gln Asp Tyr Asp Ala Ser Gln Ile Gln Val Leu Glu Gly Leu Glu Ala Va1 Arg Met Arg Pro Gly Met TyrIle GlySerThr SerLysGlu GlyLeuHis HisLeuVal Trp Glu IleVal AspAsnSer IleAspGlu AlaLeuAla GlyPheAla Ser 50 . 55 60 His IleGln ValPheIle GluProAsp AspSerIle ThrValVal Asp Asp GlyArg GlyIlePro ValAspIle GlnGluLys ThrGlyArg Pro Ala ValGlu ThrValPhe ThrValLeu HisAlaGly GlyLysPhe Gly Gly GlyGly TyrLysVal SerGlyGly LeuHisGly ValGlySer Ser Val ValAsn AlaLeuSer ThrG1nLeu AspValHis Va1HisLys Asn Gly LysIle HisTyrGln GluTyrArg ArgG1yHis ValValAla Asp S0 145 150 155 . 160 Leu GluIle ValGlyAsp ThrAspLys ThrGlyThr ThrValHis Phe $5 Thr ProAsp ProLysIle PheThrGlu ThrThrIle PheAspPhe Asp Lys Leu Asn Lys Arg Ile Gln Glu Leu Ala Phe Leu Asn Arg Gly Leu 195 ~ 200 205 Gln Ile Ser Ile Thr Asp Lys Arg Gln Gly Leu Glu Gln Thr Lys His Tyr His Tyr Glu Gly Gly Ile Ala Ser Tyr Val Glu Tyr Ile Asn Glu Asn Lys Asp Val Ile Phe Asp Thr Pro Ile Tyr Thr Asp G1y Glu Met Asp Asp Ile Thr Val Glu Val Ala Met Gln Tyr Thr Thr G1y Tyr His Glu Asn Val Met Ser Phe Ala Asn Asn Ile His Thr His Glu Gly Gly Thr His Glu Gln Gly Phe Arg Thr Ala Leu Thr Arg Val Ile Asn Asp Tyr Ala Arg Lys Asn Lys Leu Leu Lys Asp Asn Glu Asp Asn Leu Thr 305 310 315 ~ 320 Gly Glu Asp Val Arg Glu Gly Leu Thr Ala Val Ile Ser Val Lys His Pro Asn Pro Gln Phe Glu Gly Gln Thr Lys Thr Lys Leu Gly Asn Ser Glu Val Val Lys Ile Thr Asn Arg Leu Phe Ser Glu Ala Phe Ser Asp 355 360 ~ 365 Phe Leu Met Glu Asn Pro Gln Ile Ala Lys Arg Ile Val Glu Lys Gly Ile.Leu Ala Ala Lys Ala Arg Val Ala Ala Lys Arg Ala Arg Glu Val 385 . 390 395 400 Thr Arg Lys Lys Ser Gly Leu Glu Ile Ser Asn Leu Pro Gly Lys Leu Ala Asp Cys Ser Ser Asn Asn Pro Ala Glu Thr Glu Leu Phe Ile Val Glu Gly Asp Ser Ala Gly Gly Ser Ala Lys Ser Gly Arg Asn Arg Glu Phe Gln Ala Ile L_eu Pro Ile Arg Gly Lys Ile Leu Asn Val Glu Lys Ala Ser Met Asp Lys Ile Leu Ala Asn Glu Glu Ile Arg Ser Leu Phe 5$ Thr Ala Met Gly Thr Gly Phe Gly Ala Glu Phe Asp Val Ser Lys Ala 485 490 ' 495 Arg Tyr Gln Lys Leu Val Leu Met Thr Asp Ala Asp Val Asp Gly Ala His IleArg ~ThrLeuLeu LeuThrLeu IleTyrArg TyrMetLys Pro 5l5 520 525 Ile LeuGlu AlaGlyTyr ValTyrIle AlaGlnPro ProI1eTyr Gly Val LysVal GlySerGlu IleLysGlu TyrIleGln ProGlyAla Gasp 545 550 555 . 560 Gln GluIle LysLeuGln GluAlaLeu AlaArgTyr SerGluGly Arg ' Thr LysPro ThrIleGln ArgTyrLys GlyLeuGly GluMetAsp Asp His GlnLeu TrpGluThr ThrMetAsp ProGluHis ArgLeuMet Ala Arg ValSer ValAspAsp AlaAlaGlu AlaAspLys IlePheAsp Met ~$ Leu MetGly AspArgVal GluProArg ArgGluPhe IleGluGlu Asn A1a ValTyr SerThrLeu AspVal <210> 174 <211> 88 <212> PRT

35 <213> Streptococcus pneumoniae <400> 174 Met Gly ThrGlu Glu Thr Arg Phe Leu AspSer Asn Phe Val Lys Asp Lys Lys IleSer Glu Thr Thr Asp Tyr SerLeu Asn Glu Leu Val Ala Asp Lys~GlyTyrAsn Pro Ile Gln Ile Gly ValLeu Sex Asn V,al Tyr Gly Asp Pro Ala Tyr Val Pro Arg Tyr Asn Asn A1a Arg Asn Gln Ile 50 Arg Lys Tyr Glu Arg Asp 'Glu Ile Val Glu Glu Leu Val Arg Tyr Tyr Leu Lys Gly Gln Gly Val Asp Leu <210> 175 <211>

<212>
PRT

<213> pneumoniae Streptococcus <400> ' Met ValAsnTyr ProHisLys ValSerSer GlnAspArg G1nThrSer Leu SerGlnPro LysAsnPhe AlaAsnArg GlyMetSer PheGluLys Met IleAsnAla ThrAsnAsp TyrTyrLeu SerGlnGly LeuAlaVal IS Ile HisLysLys ProThrPro IleGlnIle ValGlnVal AspTyrPro Gln ArgSerArg AlaLysIle ValGluAla TyrPheArg GlnAlaSer Thr ThrAspTyr SerGlyVal TyrAsnGly TyrTyrIle AspPheGlu Val LysGluThr LysGlnLys ArgAlaIle ProMetLys AsnPheHis Pro HisGlnIle GlnHisMet GluGlnVal LeuAlaGln GlnGlyIle Cys PheVa1Leu LeuHisPhe SerSerGln GlnGluThr TyrLeuLeu Pro AlaPheAsp LeuIleArg PheTyrHis GlnAspLys GlyGlnLys Ser MetProLeu GluTyrIle ArgGluTyr GlyTyrGlu IleLysAla 165 170' 175 Gly AlaPhePro GlnIlePro TyrLeuAsn ValIleLys GluHisLeu Leu Gly Gly Lys Thr Arg <210> 176 <211> 288 <212> PRT
<213> Streptococcus pneumoniae <400> 176 Met Ala Leu Phe Ser Lys Lys Asp Lys Tyr Ile Arg Ile Asn Pro Asn Arg Ser Val Arg Glu Lys Pro Gln Ala Lys Pro Glu Val Pro Asp Glu Leu Phe Ser Gln Cys Pro Gly Cys Lys His Thr Ile Tyr Gln Lys Asp Leu G1y Ser Glu Arg Ile Cys Pro His Cys Ser Tyr Thr Phe Arg Ile Ser Ala Gln Glu Arg Leu Ala Leu Thr Ile Asp Met Gly Thr Phe Lys Glu Leu Phe Thr Gly Ile Glu Ser Lys Asp Pro Leu His Phe Pro Gly Tyr Gln Lys Lys Leu Ala Ser Met Arg Glu Lys Thr Gly Leu His Glu 100 105 110 .
Ala Val Val Thr Gly Thr Ala Leu Ile Lys Gly Gln Thr Val Ala Leu Gly Ile Met Asp Ser Asn Phe Ile Met Ala Ser Met Gly Thr Val Val Gly Glu Lys Ile Thr Arg Leu Phe Glu Tyr Ala Thr Val Glu Lys Leu Pro Val Val Leu Phe Thr Ala Ser Gly Gly Ala Arg Met Gln Glu Gly Ile Met Ser Leu Met Gln Met Ala Lys Ile Ser Ala Ala Val Lys Arg -His Ser-Asn Ala Gly Leu Phe Tyr Leu Thr Ile Leu Thr Asp Pro Thr Thr Gly Gly Val Thr Ala Ser Phe Ala Met G1u Gly Asp Ile Ile Leu 3$ 210 215 220 Ala Glu Pro Gln Ser Leu Val Gly Phe Ala Gly Arg Arg Val Ile Glu Asn Thr Val Arg Glu Ser Leu Pro Glu Asp Phe Gln Lys Ala Glu Phe Leu Leu Glu His Gly Phe Val Asp Ala Ile Val Lys Arg Arg Asp Leu Pro Asp Thr Ile Ala Ser Leu Val Arg Leu His Gly Gly Ser Pro Arg 275 ~ 280 285 <210> 177 <211> 139 5$ <212> PRT
<213> Streptococcus pneumoniae <400> 177 Met Arg Ile Met Gly Leu Asp Val Gly Ser Lys Thr Val Gly Val Ala Ile Ser Asp Pro Leu Gly Phe Thr Ala'Gln Gly Leu Glu Ile Ile Gln Ile Asn Glu Glu Gln Gly Gln Phe Gly Ser Asp Arg Val Lys Glu Leu Val Asp Thr Tyr Lys Val Glu Arg Phe Val Val Gly Leu Pro Lys Asn Met Asn Asn Thr Ser Gly Pro Arg Val Glu Ala Ser Gln Ala Tyr Gly Ala LysLeuGlu GluPhePhe GlyLeu ProValAsp GlnAspGlu Tyr Arg LeuThrThr ValAlaAla GluArg MetLeuIle GlnA1aAsp Glu Ile SerArgAsn LysArgLys LysVal IleAspLys AlaAlaGln Leu 115. l20 125 Leu IleLeuGln AsnTyrLeu AspArg LysPhe <210> 178 <211> 398 <212> PRT
<213> Streptococcus pneumoniae <400> 17s Met Ala Lys Leu Thr Val Lys Asp Val Asp Leu Lys Gly Lys Lys Val Leu Val Arg Val Asp Phe Asn Val Pro Leu Lys Asp Gly Val Ile Thr 20 25' 30 Asn Asn ArgIleThrAla AlaLeuPro ThrIleLys TyrIleIle Asp 4S Glu Gly GlyArgAlaIle LeuPheSer HisLeuGly ArgValLys Gln Glu Ala AspLysAlaGly LysSerLeu AlaProVal AlaAlaAsp Glu Leu Ala LysLeuGlyGln AspValVal PheProGly ValThrArg Ala 85 ' 90 95 Gly .GluLeuGluAlaAla IleAsnAla LeuGluAsp GlyGlnVal Ala Leu Val GluAsnThrArg TyrGluAsp ValAspGly LysLysG1u Leu Ser LysAsnAsp ProGlu LeuGlyLysTyr TrpAla SerLeuGly Asp Gly IlePheVal AsnAsp AlaPheGlyThr AlaHis ArgAlaHis Ala Ser AsnValGly IleSer AlaAsnValGlu LysAla ValAlaGly Phe ~ 165 170 175 Leu LeuGluAsn GluIle AlaTyrIleGln GluAla ValGluThr Pro 1$ Glu ArgProPhe ValAla IleLeuGlyGly SerLys ValSerAsp Lys Ile GlyValIle GluAsn Leu.LeuGluLys A1aAsp LysValLeu Ile Gly GlyGlyMet ThrTyr ThrPheTyrLys AlaGln GlyIleGlu Ile Gly AsnSerLeu ValGlu GluAs,pLysLeu AspVal AlaLysAla Leu 2S 245 ,250 255 Leu GluLysAla AsnGly LysLeuIleLeu ProVal AspSerLys Glu Ala AsnAlaPhe AlaGly TyrThrGluVal ArgAsp ThrGluGly Glu A1a ValSerGlu GlyPhe LeuGlyLeuAsp IleGly ProLysSer Ile Ala LysPheAsp GluAla LeuThrGlyAla LysThr ValValTrp Asn .

Gly ProMetGly ValPhe GluAsnProAsp PheGln AlaGlyThr Ile Gly ValMetAsp AlaIle ValLysGlnPro GlyVal LysSerIle Ile Gly GlyGlyAsp SerAla AlaAlaAlaIle AsnLeu GlyArgAla Asp Lys PheSerTrp IleSer ThrGlyGlyGly AlaSer MetGluLeu Leu Glu GlyLysVal LeuPro GlnLeuAlaAla LeuThr GluLys SS <210> 179 <211> 16'5 <212> PRT

<213> Streptococcus pneumoniae <400> 179 Met Leu Lys Ser Glu Lys Gln Ser Arg Tyr Gln Met Leu Asn Glu Glu Leu Ser Phe Leu Leu Glu Gly G1u Thr Asn Val Leu Ala Asn Leu Ser Asn AlaSerAla LeuIle LysSerArgPhe ProAsnThr ValPhe Ala Gly PheTyrLeu PheAsp GlyLysGluLeu ValLeuGly ProPhe Gln ~

Gly GlyValSer CysIle ArgIleAlaLeu GlyLysGly Va1Cys Gly 65 70 75 gp Glu AlaAlaHis PheGln GluThrValIle ValGlyAsp ValThr Thr 8'5 9 9 Tyr LeuAsnTyr IleSer CysAspSerLeu AlaLysSer G1uIle Val Val ProMetMet LysAsn GlyGlnLeuLeu GlyValLeu AspLeu Asp 115 l20 125 Ser SerGluIle GluAsp TyrAspAlaMet AspArgAsp TyrLeu Glu 130 l35 140 Gln PheValAla IleLeu LeuGluLysThr AlaTrpAsp PheThr Met Phe GluGluLys Ser <210> 180 .

<211> 209 w <2l2> PRT

<213> Streptococcus pneumoniae <400> 180 Met Thr Glu LeuLeuThr ProPheThr LysValGlu LeuGluPro Ile Glu Ile Glu LysLysArg LysGlnVal G1yIleLeu GlyGlyAsn Lys Phe Asn Val HisAsnAla HisLeuIle ValAlaAsp GlnValArg Pro Gln Gln Gly LeuAspGln ValLeuLeu MetProGlu TyrGlnPro Leu 50 ' 55 60 Pro His Asp LysLysGlu ThrIlePro GluHisHis ArgLeuLys Val 70 75 8p Met LeuGluLeu AlaIleGlu GlyIleAsp GlyLeuVal IleGluThr Ile GluLeuGlu ArgLysGly IleSerTyr ThrTyrAsp ThrMetLys 100 105 l10 Ile LeuThrGlu LysAsnPro AspThrAsp TyrTyrPhe IleIleGly 115 120 125 -' Ala AspMetVal AspTyrLeu ProLysTrp TyrArgIle AspGluLeu Val AspMetVal GlnPheVal GlyValGln ArgProArg TyrLysVal IS145 150 155 ~ 160 Gly ThrSerTyr ProValI1e TrpValAsp ValProLeu MetAspIle Ser SerSerMet ValArgAla PheLeuAla GlnGlyArg LysProAsn Phe LeuLeuPro GlnProVal LeuAspTyr IleGluLys GluGlyLeu Tyr 30 <210> 181 <21l> 255 <212> PRT

<213> Streptococcus pneumoniae 35<400> 181 Met Asn Ala LysIleVal ArgG1uAla ArgGluGln SerArgLeu Ile . 1 5 10 15 Thr Thr Asp PheAlaThr GlyIlePhe AspGluPhe IleGlnLeu Leu His Gly Arg SerPheArg AspAsp'Gly AlaValVal GlyGlyIle Asp 35 ~ 40 45 4$Gly Trp Gly AspGlnAla ValThrVal ValGlyIle GlnLysGly Leu Lys Ser Leu Gln Asp Asn Leu Lys Arg Asn Phe Gly Gln Pro His Pro Glu Gly Tyr Arg Lys Ala Leu Arg Leu Met Lys Gln Ala Glu Lys Phe Gly Arg Pro Val Val Thr Phe Ile Asn Thr Ala Gly Ala Tyr Pro Gly Val Gly Ala Glu Glu Arg Gly Gln Gly Glu Ala Ile Ala Arg Asn Leu Met GluMetSer AspLeuLys ValProIle IleAlaIle IleBileGly Glu GlyGlySer GlyGlyAla LeuAlaLeu AlaValAla AspArgVal Trp MetLeuGlu AsnSerIle TyrAlaIle LeuSerPro GluGlyPhe Ala SerIleLeu TrpLysAsp GlyThrArg AlaMetGlu AlaAlaGlu 15Leu MetLysIle ThrSerHis GluLeuLeu GluMetAsp ValValAsp Lys ValIleSer GluValGly LeuSerSer LysGluLeu IleLysSer , ' Val LysLysGlu LeuGlnThr GluLeuAla ArgLeuSer GlnLysPro Leu GluGluLeu LeuGluGlu ArgTyrGln ArgPheArg LysTyr <210> 182 <2l1> 169 <212> PRT

<213> Streptococcus pneumoniae <400> 182 Met Ile Lys ValGluMet AlaAspVal GluValLeu AlaLysIle Ile Ala Lys Thr PheArgGlu ThrPheAla TyrAspAsn ThrGluGlu Gln 40Gln Leu Glu TyrPheGlu GluAlaTyr SerLeuLys ThrLeuSer Gln Thr Glu Gly AsnProAsp SerGluThr TyrPheIle MetHisGlu Leu Glu Glu Ala GlyPheLeu LysValAsn TrpGlySer AlaGlnThr Ile ~Glu Arg Glu Leu Glu Asp Ala Phe Glu Ile Gln Arg Leu Tyr Val Leu 5~ 85 90 95 Gln Lys Phe Gln Gly Phe Gly Leu Gly Lys Gln Leu Phe Glu Phe Ala 55 Leu Glu Leu Ala Thr Lys Asn Ser Phe Ser Trp Ala Trp Leu Gly Val Trp Glu His Asn Thr Lys Ala Gln Ala Phe Tyr Asn Arg Tyr Gly Phe Glu Lys Phe Ser Gln His His Phe Met Val Gly Gln Lys Val Asp Thr Asp Trp Leu Leu Arg Lys Lys Leu Arg l65 <210> 183 <211> 529 <212> PRT
<2l3> Streptococcus pneumoniae <400> 183 Met Leu Arg Gly Thr Ala Leu Leu Thr Ala Ser Asn Phe Ile Ser Arg 1 5 . 10 15 Leu Leu Gly Ala Val Tyr I7.e Ile Pro Trp Tyr Ile Trp Met Gly Ala Tyr Ala Ala Lys Ala Asn Gly Leu Phe Thr Met Gly Tyr Thr Ile Tyr 35 40 ' 45 Ala Trp Phe Leu Leu Val Ser Thr Ala Gly Ile Pro Val Ala Val Ala Lys Gln Val Ala Lys Tyr Asn Thr Met Arg Glu Glu Glu His Ser Phe Ala Leu Ile Arg Ser Phe Leu Gly Phe Met Thr Gly Leu Gly Leu Val 5 Phe Ala Leu Val Leu~Tyr Val Phe Ala Pro Trp Leu Ala Asp Leu Ser 100 . 105 110 Gly ValGlyLys AspLeuIle ProIleMet GlnSerLeu AlaTrpGly Val LeuthePhe ProSerMet SerValIle ArgGlyPhe PheGlnGly Met AsnAsnLeu LysProTyr AlaMetSer GlnIleAla GluGlnVal Ile ArgValIle TrpMetLeu LeuAlaThr PheIleIle MetLysLeu SO Gly SerGlyAsp TyrLeuAla AlaValThr GlnSerThr PheAlaAla 180 ' 185 190 Phe ValGlyMet ValAlaSer PheAlaVal LeuIle,TyrPheLeuAla 195 . 200 205 5$

Gln GluSerSer LeuLysArg ValPheGlu ThrGlyAsp LysIleAsn Ser Lys Arg Leu Leu Val Asp Thr Ile Lys Glu Ala Ile Pro Phe I1e Leu Thr Gly Ser Ala Ile Gln Ile Phe Gln Ile Leu Asp Gln Leu Thr 245 250' 255 Phe Ile Asn Ser Met Ser Trp Phe Thr Asn Tyr Ser Asn Glu Asp Leu Val Val Met Phe,Ser Tyr Phe Ser Ala Asn Pro Asn Lys Ile Thr Met . 275 280 285 Ile Leu Ile Ser Val Gly Val Ser Ile Gly Ser Val Gly Leu Pro Leu Leu Thr Glu Asn Tyr Val Lys Gly Asp Leu Lys Ala Ala Ser Arg Leu Val Gln Asp Ser Leu Thr Leu Leu Phe Met Phe Leu Leu Pro Ala Thr Val Gly Val Val Met Val Gly Glu Pro Leu Tyr Thr Val Phe Tyr Gly Lys Pro Asp Ser Leu Ala Leu Gly Leu Phe Val Phe Ala Val Leu Gln Ser I1e Ile Leu G1y Leu Tyr Met Val Leu Ser Pro Met Leu Gln Ala Met Phe Arg Asn Arg Lys A1a Val Leu Tyr Phe Ile Tyr Gly Ser Ile 3$ Ala Lys Leu Val Leu Gln Leu Pro Thr Ile Ala Leu Phe His Ser Tyr Gly Pro Leu Ile Ser Thr Thr Ile Ala Leu Ile Ile Pro Asn Val Leu Met Tyr Arg Asp Ile Cys Lys Val Thr Gly Val Lys Arg Lys Val Ile Leu Lys Arg Thr Ile Leu Ile Ser Leu Leu Thr Leu Val Met Phe Leu Leu Ile Gly Thr Ile Gln Trp Leu Leu Gly Phe Phe Phe Gln Pro Ser $0 Gly Arg Leu Trp Ser Phe Phe Tyr Val Ala Leu Val Gly Ala Met Gly Gly Gly Leu Tyr Met Val Met Ser Leu Arg Thr Tyr Leu Leu Asp Lys Val Ile Gly Lys Ala Gln Ala Asp Arg Leu Arg Ala Lys Phe Lys Leu Ser <210> 184 <211> 155 <212> PRT.
<213> Streptococcus pneumoniae <400> 184 Met Ser Asp Lys Ile Gly Leu Phe Thr Gly Ser Phe Asp Pro Met Thr 1 5 10 ~ 15 Asn Gly His Leu Asp Ile Ile Glu Arg Ala Ser Arg Leu Phe Asp Lys Leu Tyr Val Gly Ile Phe Phe Asn Pro His Lys Gln Gly Phe Leu Pro 20 .

Ile GluAsnArg LysArgGly LeuGluLys A1aLeuGly HisLeuGlu Asn ValGluVal ValAlaSer HisAspGlu LeuValVal AspValAla Lys ArgLeuGly AlaThrCys LeuValArg GlyLeuArg AsnAlaSer Asp LeuGlnTyr GluAlaSer PheAspTyr TyrAsnHis GlnLeuSer Ser AspIleGlu ThrIleTyr LeuHisSer ArgProGlu HisLeuTyr Ile SerSerSer GlyValArg GluLeuLeu LysPheGly GlnAspIle Ala CysTyrVal ProGluSer IleTrpArg Lys <210>

<211>

<212>
PRT

<213> pneumoniae Streptococcus <400>

Met ThrIleLeu PheValVal IleSerAla SerPheLeu TyrMetVal 1 5 , 10 15 Ser LeuSerMet LysProTyr GlnThrAla LysSerGlu.GlyGluLys Leu AlaGlnGln TyrAlaGly LeuGluGln AlaAspGln Va1AspLeu ~

35 40 ~ 45 127 .

Tyr Asn Gly Leu Glu Ser Tyr Tyr Ser Val Leu Gly Arg Asn Lys Gln Gln Glu AlaLeuAla ValLeu IleGlyLys AspAspHis LysIleTyr Val Tyr GlnLeuAsn GlnGly ValSerGln GluLysAla GluThrVal 10Ser Lys GluLysGly AlaGly GluIleAsp LysIleIle PheGlyArg Tyr Gln AspLysPro IleTrp GluValLys SerGlySer AspPheTyr Leu Val AspPheGlu ThrGly AlaLeuVal AsnLysGlu GlyLeu <210> 186 <211>

<212>
PRT

<213> pneumoniae Streptococcus <400>

Met IleAspI1e HisSerHis IleValPhe AspValAsp AspGly Pro Lys SerArgGlu GluSerLys AlaLeuLeu ThrGluAla TyrArg Gln Gly ValArgThr 21eValSer ThrSerHis ArgArgLys GlyMet Phe Glu ThrProGlu GluLysIle AlaGluAsn PheLeuGln ValArg Glu Ile AlaLysGlu ValAlaSex Asp.LeuVal IleAla~TyrGlyAla Glu Ile TyrTyrThr ProAspVal LeuAspLys LeuGluAsn AsnArg Ile Pro ThrLeuAsn AsnSerArg TyrAlaLeu TleGluPhe SerMet Asn Thr ProTyrArg AspIleHis SerAlaLeu AsnLysIle LeuMet Leu Gly IleThrPro ValIleAla HisIleGlu ArgTyrAsp ValLeu Glu Asn AsnGluLys ArgValArg GluLeuIle AspMetGly CysTyr Thr SS

Gln IleAsnSer SerHisVal LeuLysSer LysLeuPhe Gly~Glu Pro Tyr Lys Phe Met Lys Lys Arg Ala Gln Tyr Phe Leu Glu Arg Asp Leu Val His Ile Ile Ala Ser Asp Met His Asn Val Asp Gly Arg Pro Pro l95 200 205 His Met Ala Glu Ala Tyr Asp Leu Val Ser Gln Lys Tyr Gly Glu Ala Lys Ala Gln Glu Leu Phe I1e Asp Asn Pro Arg Lys Ile Val Met Asp Gln Leu Ile <210> 187 <211> 308 <212> PRT
<213> Streptococcus pneumoniae <400> 187 Met Ser Thr Ile Asp Lys Glu Lys Phe Gln Phe Val Lys Arg Asp Asp Phe Ala Ser Glu Thr Ile Asp Ala Pro Ala Tyr Ser Tyr Trp Lys Ser 20 ~ 25 30 Val Phe Lys Gln Phe Met Lys Lys Lys Ser Thr Val Val Met Leu Gly Ile Leu Val Ala I1e Ile Leu Ile Ser Phe Ile Tyr Pro Met Phe Ser Lys Phe Asp Phe Asn Asp Val Ser Lys Val Asn Asp Phe Ser Val Arg Tyr Ile Lys Pro Asn Ala Glu His Trp Phe Gly Thr Asp Ser Asn Gly Lys Ser Leu Phe Asp Gly Val Trp Phe Gly Ala Arg Asn Ser Ile Leu Ile Ser Val Ile Ala Thr Val Ile Asn Leu Val Ile Gly Val Phe Val Gly Gly Ile Trp Gly Ile Ser Lys Ser Val Asp Arg Val Met Met Glu Val Tyr Asn Val Ile Ser Asn Ile Pro Pro L,eu Leu Ile Val Ile Val Leu Thr Tyr Ser Ile Gly Ala Gly Phe Trp Asn Leu Ile Phe Ala Met Ser Val Thr Thr Trp Ile Gly Ile Ala Phe Met Ile Arg Val Gln Ile Leu ArgTyrArg AspLeu GluTyrAsn LeuAlaSerArg ThrLeu Gly Thr ProThrLeu LysIle ValAlaLys AsnIleMetPro GlnLeu Val 210 . 215 220 Ser ValIleVal ThrThr MetThrGln MetLeuProSer PheIle Ser Tyr GluAlaPhe LeuSer PhePheGly LeuGlyLeuPro IleThr Val Pro SerLeuGly ArgLeu IleSerAsp TyrSerGlnAsn ValThr Thr Asn AlaTyrLeu PheTrp IleProLeu ThrThrLeuVal LeuVal Ser Leu SerLeuPhe ValVal GlyGlnAsn LeuAlaAspAla SerAsp Pro Arg ThrHisArg <210>
l88 <211>

<212>
PRT

<213> pneumoni ae Streptococcus <400>

Met TyrAsnLeu LeuLeu ThrIleLeu LeuValLeuSer ValVal Ile Val IleAlaIle PheMet GlnProThr LysAsnGlnSer SerAsn Val Phe AspAlaSer SerGly AspLeuPhe GluArgSerLys AlaArg Gly Phe GluAlaVal MetGln ArgLeuThr GlyIleLeuVal PhePhe Trp Leu AlaIleAla LeuAla ~LeuThrVal LeuSerSerArg ~

50 <210> 189 <211> 369 <212> PRT
<213> Streptococcus pneumoniae SS <400> 189 Met Phe Arg Arg Asn Lys Leu Phe Phe Trp Thr Thr Glu Ile Leu Leu Leu Thr Ile Ile Phe Tyr Leu Trp Arg Gln Met Gly Ser Leu I1e Asn ,5 Pro Phe Val Ser Val Leu Asn Thr Ile Met Ile Pro Phe Leu Leu Gly Gly Phe Leu Tyr Tyr Leu Thr Asn Pro Ile Val Thr Phe Leu Asn Lys 50 55 ' 60 Val Cys Lys Leu Asn Arg Leu Leu Gly Ile Leu Ile Thr Leu Cys Thr Leu Val Trp Gly Met Val Ile G1y Val Val Tyr Leu Leu Pro Ile Leu Ile Asn Gln Leu Ser Ser Leu Ile Ile Ser Ser Gln Thr Ile Tyr Ser l00 105 . 110 Arg Val Gln Asp Leu Ile Ile Asp Leu Ser Asn Tyr Pro Ala Leu Gln Asn Leu Asp Val Glu A1a Thr Ile Gln Gln Leu Asn Leu Ser Tyr Val Asp Ile Leu Gln Asn I1e Leu Asn Ser Val Ser Asn Ser Val Gly Ser Val Leu Ser Ala Leu Ile Ser Thr Val Leu Ile Leu Ile Met Thr Pro Val Phe Leu Val Tyr Phe Leu Leu Asp Gly His Lys Phe Leu Pro.Met Leu Glu Arg Thr Tle Leu Lys Arg Asp Arg Leu His Ile Ala Gly Leu Leu Lys Asn Leu Asn Ala Thr Ile Ala Arg Tyr Ile Ser Gly Val Ser Ile Asp Ala Ile Ile Ile Gly Cys Leu Ala Tyr. Ile Gly Tyr Ser Ile Ile Gly Leu Lys Tyr Ala Leu Val Phe Ala Ile Phe Ser Gly Val A1a Asn Leu Ile Pro Tyr Val Gly Pro Ser Ile Gly Leu Ile Pro Met Ile 260 2.65 270 $0 Ile Ala Asn Ile Phe Thr Val Pro His Arg Leu Leu Ile Ala Val Ile Tyr Met Leu Val Val Gln Gln Val Asp Gly Asn Ile Leu Tyr Pro Arg Ile Val Gly Ser Val Met Lys Val His Pro Ile Thr Ile Leu Val Leu 305 ~ 310 315 320 Leu Leu Leu Ser Ser Asn Ile Tyr Gly Val Val Gly Met Ile Val Ala Val Pro Thr Tyr Ser Ile Leu Lys Glu Ile Ser Lys Phe Leu Ser Arg Leu Tyr Glu Asn His Lys Ile Met Lys Glu Arg Glu Arg Glu Leu Ala 355 . 360 365-Lys <210> 190 <211> 451 <212> PRT
<213> Streptococcus pneumoniae <400> 190 Met Tyr Gln Ala Leu Tyr Arg Lys Tyr Arg Ser Gln Asn Phe Ser Gln Leu Val Gly Gln Glu Val Val Ala Lys Thr Leu Lys Gln Ala Val Glu ~S 20 25 30 G1n Glu Lys Ile Ser His Ala Tyr Leu Phe Ser G1y Pro Arg Gly Thr 30 Gly Lys Thr Ser Val Ala Lys Ile Phe Ala Lys Ala Met Asn Cys Pro Asn Gln Val Gly G1y Glu Pro Cys Asn Asn Cys Tyr Ile Cys Gln Ala Val Thr Asp Gly Ser Leu Glu Asp Val Ile Glu Met Asp Ala Ala Ser Asn Asn Gly Val Asp Glu Ile Arg Glu Ile Arg Asp Lys Ser Thr Tyr Ala Pro Ser Leu Ala Arg Tyr Lys Val Tyr Ile Ile Asp Glu Val His Met Leu Ser Thr Gly Ala Phe Asn Ala Leu Leu Lys Thr Leu Glu Glu Pro Thr Gln Asn Val Val Phe Ile Leu Ala Thr Thr Glu Leu His Lys 145 150 155 l60 SO
Ile Pro Ala Thr Ile Leu Ser Arg Val Gln Arg Phe Glu Phe Lys Ser Ile Lys Thr Gln Asp Ile Lys Glu His Ile His Tyr Ile Leu Glu Lys Glu Asn Tle Ser Ser Glu Pro Glu Ala Val Glu Ile Ile Ala Arg Arg Ala Glu Gly G1y Met Arg Asp A1a Leu Ser I1e Leu Asp Gln Ala Leu Ser Leu Thr Gln Gly Asn Glu Leu Thr Thr Ala Ile Ser Glu Glu T1e Thr Gly Thr Ile Ser Leu Ser Ala Leu Asp Asp Tyr Val Ala A1a Leu Ser Gln Gln Asp Val Pro Lys Ala Leu Ser Cys Leu Asn Leu Leu Phe 260 265. 270 IS Asp Asn Gly Lys Ser Met Thr Arg Phe Val Thr Asp Leu Leu His Tyr Leu Arg Asp Leu Leu Ile Val Gln Thr Gly Gly Glu Asn Thr His His Ser Ser Val Phe Val Glu Asn Leu A1a Leu Pro Gln Lys Asn Leu Phe Glu Met Ile Arg Leu Ala Thr Val Asn Leu Ala Asp Ile Lys Ser Ser Leu Gln Pro Lys Ile Tyr A1a Glu Met Met Thr~Val Arg Leu Ala Glu Ile Lys Pro Glu Pro Ala Leu Ser Gly Ala Val Glu Asn Glu Ile Ala Thr Leu Arg Gln Glu Val Ala Arg Leu Lys Gln Glu Leu Ser Asn Ala Gly Ala Val Pro Lys Gln Val Ala Pro Ala.Pro Ser Arg Pro Ala Thr Gly Lys Thr Val Tyr Arg Val Asp Arg Asn Lys Val Gln Ser Ile Leu Gln Glu Ala Val Glu Asn Pro Asp Leu Thr Arg Gln Asn Leu Ile Arg Leu Gln Asn Ala Trp Gly Glu Val Ile Glu Ser Leu Gly Gly Pro Asp Lys Leu Cys <210> 191 <211> 662 <212> PRT
'JS <213> Streptococcus pneumoniae <400> 191 Met Phe Arg Leu Thr Asn Lys Leu Ala Val Ser Asn Leu Ile Lys Asn Arg LysLeu TyrTyrPro PheAlaLeu AlaValLeu LeuAlaVal Thr Leu ThrTyr LeuPheTyr SerLeuThr PheAsnPro LysIleAla Glu 1~ Ile ArgGly GlyThr~ThrIleGlnAla ThrLeuGly PheGlyMet Phe Val ValThr LeuAlaSer AlaIleIle ValLeuTyr AlaAsnSer Phe Val MetLys LysArgSer LysGluLeu GlyIleTyr GlyMetLeu Gly Leu GluLys ArgHisLeu IleSerMet ThrPheLys GluLeuVal Val 2~ 100 105 110 Phe GlyIle LeuThrVal GlyAlaGly IleGlyIle GlyAlaLeu Phe Asp LysLeu IlePheAla PheLeuLeu LysLeuMet LysLeuLys Va1 Glu LeuVal AlaThrPhe GlnThrLys ValValIle ThrValLeu Val 145 150 . 155 160 Val PheGly LeuIlePhe LeuGlyLeu MetPheLeu AsnAlaLeu Arg Ile AlaArg MetAsnAla LeuGlnLeu SerArgGlu LysAlaSer Gly Glu LysLys GlyArgPhe LeuProLeu GlnThrIle LeuGlySer Ile 4~ Ser LeuGly IleGlyTyr TyrLeuAla LeuThrVal LysAspPro Leu Thr AlaLeu ThrThrPhe PheIleAla ValLeuLeu ValIlePhe Gly .

Thr TyrLeu LeuPheAsn AlaGlyIle ThrValPhe LeuGlnTle Leu Lys LysAsn LysLysTyr TyrTyrGln ProAsnAsn LeuIleSer Val S~ 260 265 270 Ser AsnLeu IlePheArg MetLysLys AsnAlaVal GlyLeuAla Thr 55~Ile AlaIle LeuSerThr MetValLeu ValThrMet SerAlaAla Thr Ser Ile Phe Asn Ser Ala Glu Ser Phe Lys Lys Val Leu Asn Pro His 305 310 3l5 320 Asp Phe Gly Val Ser Gly Gln Asn Val Glu Lys Glu Asp Leu Asp Lys Leu Leu Ser G1n Phe Ala Ser Asp Asn Gly Tyr Lys Ile Lys Glu Lys IO Glu Val Phe Arg Tyr Thr Tyr Phe Gly Val Ala Asn Gln Glu Gly Asn Lys Leu Thr Phe Phe Glu Lys Gly Gln Asn Arg Val Gln Pro Thr Thr Val Phe Met Val Phe Asp Gln Lys Asp Tyr Glu Asn Met Thr Gly Gln 385 ~ 390 395 400 Lys Leu Ser Leu Ser Gly Asn Glu Val Gly Leu Phe Ala Lys Asn Asp Gly Leu Lys G1y GIn Lys Thr Leu Ile Leu Asn Asp His Gln Phe Ser Val Lys Glu Glu Phe Asn Lys Asp Phe Ile Val Asn His Val Pro Asn Gln Phe Asn I1e Leu Thr Ala Asp Tyr Asn Tyr Leu Val Val Pro Asp Leu Gln Ala Phe Leu Asn Gln Phe Pro Asp Ser Asp Ile Tyr Asn Gln Phe Tyr Gly Gly Met Asn Val Asn Va1 Ser Glu Glu Glu Gln Leu Lys 35. 485 490 495 Val Ala Glu Glu Tyr Glu Asn Tyr Leu Asn G1n Phe Asn Ala Gln Leu 4~ Asp Thr Glu Gly Ser Tyr Val Tyr Gly Ser Asn Leu Ala Asp Ala Ser Ser Gln Met Ser Ala Leu Phe Gly Gly Val Phe Phe Ile Gly Ile Phe Leu Ser Ile Ile Phe Met Val Gly Thr Val Leu Val Tle Tyr Tyr Lys.

Gln Ile Ser Glu Gly Tyr Glu Asp Arg Glu Arg Phe Ile Ile Leu Gln Lys Val Gly Leu Asp Gln Lys Gln Ile Lys Gln Thr Ile His Lys Gln 5$ Val Leu Thr Val Phe Phe Leu Pro Leu Leu Phe Ala Phe I1e His Leu Ala Phe Ala Tyr His Met Leu Ser Leu Ile Leu Lys Val Ile Gly Val Leu Asp Thr Thr Met Met Leu Ile Val Thr Leu Ser Ile Cys Ala Ile Phe Leu Ile Ala Tyr Val~Leu Ile Phe Met Tle Thr Ser Arg Ser Tyr Arg Lys Ile Val Gln Met <210> 192 IS <211> 296 <212> PRT
<213> Streptococcus pneumoniae <400> 192 Met Lys Gln Asp Gln Leu Lys Ala Trp Gln Pro Ala Gln Phe Asp Arg Phe Val Arg Ile Leu G1u Gln Asp Gln Leu Asn His Ala Tyr Leu Phe Ser GlyPhePhe GlySerLeu GluMetAla GlnPheLeu AlaLysSer 35 ~ 40 45 Leu PheCysThr AspLysVal GlyValLeu ProCysGlu LysCysArg Ser CysLysLeu IleGluGln G1uGluPhe ProAspVal ThrLeuIle 6'S 70 75 80 Lys ProValAsn GlnValIle LysThrGlu ArgI1eArg GluLeuVal Gly GlnPheSer GlnAlaGly IleGluSer GlnG1nGln ValPheIle 100 . 105 110 Ile GluGlnAla AspLysMet HisProAsn AlaAlaAsn SerLeuLeu Lys Va1IleGlu GluProGln SerGluVa1 TyrIlePhe PheLeuThr Ser AspGluGlu LysMetLeu ProThrIle ArgSerArg ThrGlnIle Phe HisPheLys LysGlnGlu GluLysLeu IleLeuLeu LeuGluGlh Met GlyLeuVal LysLysLys AlaThrLeu LeuAlaLys PheSerGln Ser ArgAlaGlu AlaGluLys'LeuAlaAsn GlnAlaSer PheTrpThr Leu Val Asp Glu Ser Glu Arg Leu Leu Thr Trp Leu Val Ala Lys Lys Lys GluSerTyr LeuGlnVal AlaLysLeu AlaAsnLeu AlaAspAsp Lys GluLysGln AspGlnVal LeuArgIle LeuGluVal LeuCysGly ~

Gln AspLeuLeu GlnValArg ValArgVal IleLeuGln AspLeuLeu Glu AlaArgLys MetTrpGln AlaAsnVal SerPheGln AsnAlaMet G1u TyrLeuVal LeuLysGlu Ile 2~
<210>

<211>

<212>
PRT

<213> pneumoniae Streptococcus <400>

Met AsnSer PheZysAsn PheLeuLysGlu TrpGly LeuPheLeu Leu 30 Ile LeuSer LeuLeuAla LeuSerArgIle PhePhe TrpSerAsn Val Arg ValGlu GlyHisSer MetAspProThr LeuAla AspGlyGlu Ile 35 40 ~ 45 Leu PheVal ValLysHi'sLeuProIleAsp ArgPhe AspIleVal Val Ala HisGlu GluAspGly AsnLysAspIle ValLys ArgValIle Gly 65 70' 75 80 Met ProGly AspThrIle ArgTyrGluAsn AspLys LeuTyrIle Asn 45 Asp LysGlu ThrAspGlu ProTyrLeuAla AspTyr TleLysArg Phe Lys AspAsp LysLeuGln SerThrTyrSer GlyLys GlyPheGlu Gly $~

Asn LysGly ThrPhePhe ArgSerIleAla GlnLys AlaGlnAla Phe Thr ValAsp ValAsnTyr AsnThrAsnPhe SerPhe ThrValPro Glu Gly GluTyr LeuLeuLeu GlyAspAspArg LeuVal SerSerAsp Ser 165 170 . 175 Arg His Val Gly Thr Phe Lys Ala Lys Asp Ile Thr Gly Glu.Ala Lys 180 .185 190 Phe Arg Phe Trp Pro Ile Thr Arg Ile Gly Thr Phe <210> 194 <2l1> 328 <212> PRT
<213> Streptococcus pneumoniae IS <400> 194 Met Val Val Phe Thr Gly Ser Thr Val Glu Glu Ala Ile Gln Lys Gly_ Leu Lys Glu Leu Asp Ile Pro Arg Met Lys Ala His Ile Lys Val Ile Ser Arg Glu Lys Lys Gly Phe Leu Gly Leu Phe Gly Lys Lys Pro Ala Gln Val Asp Ile Glu Ala Ile Ser Glu Thr Thr Val Val Lys Ala Asn Gln Gln Val Val Lys Gly Val Pro Lys Lys Ile Asn Asp Leu Asn Glu Pro Val Lys Thr Val Ser Glu Glu Thr Val Asp Leu Gly His Val Val Asn Ala Ile Lys Lys Ile Glu Glu Glu Gly Gln Gly Ile Ser Asp Glu Val Lys Ala Glu Ile Leu Lys His Glu Arg His Ala Ser Thr Ile Leu Glu Glu Thr Gly His Ile Glu Ile Leu Asn Glu Leu Gln Ile Glu Glu Ala Met Arg Glu Glu Ala Gly Ala Asp Asp Leu Glu Thr Glu Gln Asp Gln Thr Glu Asn Gln Asp Leu Lys Glu Met Gly Leu Lys Val Glu Gln 165 170 ~ 175 Ser Tyr Asp Ile Ala Gl.n Val Ala Thr Asp Val Thr~Ala Tyr Val Gln Ala Ile Val Asp Asp Met Asp Val Glu Ala Thr Leu Ser Asn Asp Tyr 195 200 2.05 SS Asn Arg Arg Ser Ile Asn Leu Gln Ile Asp Thr Asn Glu Pro Gly Arg Ile Ile Tyr HisGlyLys ValLeuLys AlaLeuGln LeuLeuAla Gly Gln Asn Leu TyrAsnArg TyrSerLys ThrPheTyr ValThrIle Tyr S 245 250 ~ 255 Asn Val Asp TyrValGlu HisArgAla GluValLeu GlnThrTyr Asn 10Ala Gln Leu A1'aAsnArg ValLeuGlu GluGlyArg SerHisLys Lys Thr Asp Met SerAsnSer GluArgLys IleIleHis ArgIleIle Pro Ser Arg Asp GlyValThr SerTyrSer GluGlyAsp GluProAsn Met Arg Tyr Val ValAspThr Glu Val <210> 195 <211> 460 25<212> PRT

<213> Streptococcus pneumoniae <400> 195 Met Ser Phe AlaIleIle LeuAlaAla GlyLysGly ThrArgMet Asn Lys Ser Asp Leu Pro Lys Val Leu His Lys Val Ala Gly Ile Ser Met 3$ Leu GluHisVal PheArgSer ValGlyAla IleGlnPro GluLysThr Val ThrValVal GlyHisLys AlaGluLeu ValGluGlu ValLeuAla Gly GlnThrGlu PheValThr GlnSer.Glu GlnLeuGly ThrGlyHis 65 70 75 g0 Ala ValMetMet ThrGluPro IleLeuGlu G1yValSer GlyHisThr Leu ValIleAla GlyAspThr ProLeuI1e ThrGlyGlu SerLeuLys SO Asn LeuIleAsp PheHisIle AsnHisLys AsnValAla ThrIleLeu Thr AlaGluThr AspAsnPro PheGlyTyr GlyArgIle ValArgAsn Asp AsnAlaGlu ValLeuArg SerLeuLeu SerArgArg MetLeuGln 145 150 155 ~ 160 Ile Leu Lys Ser Lys Ser Arg Lys Ser Thr Leu Val Thr Tyr Val Phe Asp AsnGlu ArgLeuPhe GluAlaLeu LysAsnIle AsnThrAsn Asn Ala GlnGly GluTyrTyr IleThrAsp ValIleGly IlePheArg Glu Thr GlyGlu LysValGly AlaTyrThr LeuLysAsp PheAspGlu Ser Leu GlyVal AsnAspArg ValAlaLeu AlaThrAla GluSerVal Met Arg ArgArg IleAsnHis LysHisMet ValAsnGly ValSerPhe Val Asn PxoGlu AlaThrTyr IleAspIle AspValGlu IleAlaPro Glu 260 265 ~ 270 Val GlnIle GluAlaAsn ValIleLeu LysGlyGln ThrLysIle Gly ~

Ala GluThr ValLeuThr AsnGlyThr TyrValVal AspSerThr Ile Gly AlaGly AlaValIle ThrAsnSer MetIleGlu ~GluSerSer Val Ala AspGly ValThrVal GlyProTyr AlaHisIle ArgProAsn Ser 325 330~ 335 Ser LeuGly AlaGlnVal HisIleGly AsnPheVal GluValLys Gly Ser SerIle GlyGluAsn ThrLysAla GlyHisLeu ThrTyrIle Gly Asn CysGlu ValGlySer AsnValAsn PheGlyAla GlyThrIle Thr Val AsnTyr AspGlyLys AsnLysTyr LysThrVal IleGlyVal Asn Val PheVal GlySerAsn SerThrIle IleAlaPro ValGluLeu Gly Asp AsnSer LeuValGly AlaGlySer ThrIleThr LysAspVal Pro Ala AspAla IleAlaIle GlyArgGly ArgGlnIle AsnLysAsp Glu SS

Tyr AlaThr ArgLeuPro HisHisPro LysAsnGln <210> 196 <211> 311 <212> PRT
<21'3> Streptococcus pneumoniae <400> l96 Met Ser Lys Ile Leu Val Phe Gly His Gln Asn Pro Asp Ser Asp Ala Ile Gly Ser.Ser Val Ala Phe Ala Tyr Leu Ala Lys Glu Ala Tyr Gly Leu Asp Thr Glu Ala Val Ala Leu Gly Thr Pro Asn Glu Glu Thr Ala Phe Val Leu Asn Tyr Phe Gly Val Glu Ala Pro Arg Val Ile Thr Ser Ala Lys Ala Glu Gly Ala Glu Gln Val Ile Leu Thr Asp His Asn Glu Phe Gln Gln Ser Val Ser Asp Ile Ala Glu Val Glu Val Tyr Gly Val Val Asp His His Arg Val Ala Asn Phe Glu Thr Ala Ser Pro Leu Tyr Met Arg Leu Glu Pro Val Gly Ser Ala Ser~ Ser Ile Val Tyr Arg Met Phe Lys Glu His Gly Val Ala Val Pro Lys Glu Ile Ala Gly Leu Met Leu Ser Gly Leu Ile Ser Asp Thr Leu Leu Leu Lys Ser Pro Thr Thr His Pro Thr Asp Lys Ile Ile Ala Pro Glu Leu Ala Glu Leu Ala Gly Val Asn heu Glu Glu Tyr Gly Leu Ala Met Leu Lys Ala Gly Thr Asn ~$ Leu Ala Ser Lys Ser Ala Glu Glu Leu Ile Asp Ile Asp Ala Lys Thr Phe Glu Leu Asn Gly Asn Asn Val Arg Val Ala Gln Val Asn Thr Val Asp Ile Ala Glu Val Leu Glu Arg Gln Ala Glu Ile Glu Ala Ala Met Gln Ala Ala Asn Glu Ser Asn Gly Tyr Ser Asp Phe Val Leu Met Ile Thr Asp Ile Val Asn Ser Asn Ser Glu Ile Leu Ala Leu Gly Ala Asn Met Asp Lys Val Glu Ala Ala Phe Asn Phe Lys Leu Glu Asn Asn His $.
Ala Phe Leu Ala Gly Ala Val Ser Arg Lys Lys Gln Val Val Pro Gln Leu Thr Glu Ser Phe Asn Thr 305 3l0 <210>

<21 1> 25 IS <21 2> RT
P

<21 3> treptococcuspneumoniae S

<40 0> 97 Met IleSer LysArg LeuGluLeu ValAlaSer PheValSerGln Gly 20,1 5 10 15 Ala IleLeu LeuAsp ValGlySer AspHisAla TyrLeuProTle Glu 20 25 , 30 2$ Leu ValGlu ArgGly GlnIleLys SerAlaIle AlaGlyGluVal Val Glu GlyPro TyrGln SerAlaVal LysAsnVal GluAlaHisGly Leu Lys GluLys IleGln ValArgLeu AlaAsnGly LeuAlaAlaPhe Glu ~

65 70 75 gp Glu ThrAsp GlnVal SerValIle ThrIleAla GlyMetGlyGly Arg Leu IleAla ArgIle LeuGluGlu GlyLeuGly LysLeuAlaAsn Val 40 Glu ArgLeu TleLeu GlnProAsn AsnArgGlu AspAspLeuArg Ile Trp LeuGln AspHis GlyPheGln IleValAla GluSerIleLeu Glu G1u Al.aGly LysPhe TyrGluIle LeuVal~Val GluAlaGlyGln Met 145 150, 155 160 Lys LeuSer AlaSer AspValArg PheGlyPro PheLeuSerLys Glu Val SerPro ValPhe Val~GlnLys TrpGlnLys GluAlaGluLys Leu SS Glu PheAla LeuGly GlnIlePro GluLysAsn LeuGluGluArg Gln Val Leu Val Asp Lys Ile Gln Ala Ile Lys Glu Val Leu His Val Ser Lys <210> 198 <211> 161 <212> PRT

<213> Streptococcus pneumoniae <400> 198 Met Asn Asn AspIle Lys LeuMet Thr Gln AspGln Leu Asp Phe Ser IS 1 5 . 10 15 Ser Leu Glu PheSer Tyr AsnGly Thr Asp LeuGln Arg Lys Glu Phe Ser Lys Glu AlaArg Pro ProGlu Val Ala GlnVal Asn Val Thr Ala Pro Ala Pro Val Leu Ala Thr Pro Ser Pro Val Ala Pro Thr Ser Ala Pro AlaGluThr ValAlaGlu GluValPro AlaProAla GluAlaSer Val AlaSexGlu GlyAsnLeu ValGluSer ProLeuVal GlyValVal Tyr LeuAlaAla GlyProAsp LysProAla PheValThr ValGlyAsp Ser ValLysLys GlyGlnThr LeuValIle TleGluAla MetLysVa1 Met AsnGluIle ProAlaPro LysAspGly ValValThr GluIleLeu Val SerAsnGlu GluMetVal GluPheGly LysGlyLeu ValArgIle 145 150 155' - 160 Lys <210> 199 <211> 4l1 .
<212> PRT
<213> Streptococcus pneumoniae <400> 199 Met Lys Leu Asn Arg Val Val Val Thr Gly Tyr Gly Val Thr Ser Pro Ile Gly Asn Thr Pro Glu Glu Phe Trp Asn Ser Leu Ala Thr Gly Lys Ile Gly Ile Gly Gly Ile Thr Lys Phe Asp His Ser Asp Phe Asp Val His Asn Ala Ala Glu Ile Gln Asp Phe Pro Phe Asp Lys Tyr Phe Val Lys Lys Asp Thr Asn Arg Phe Asp Asn Tyr Ser Leu Tyr Ala Leu Tyr Ala Ala Gln Glu Ala Val Asn His Ala Asn Leu Asp Val Glu Ala Leu IS Asn Arg Asp Arg Phe Gly Val Ile Val A1a Ser Gly Ile Gly Gly Ile Lys Glu Ile Glu Asp Gln Val Leu Arg Leu His Glu Lys Gly Pro Lys 115 l20 125 Arg Val Lys Pro Met Thr Leu Pro Lys Ala Leu Pro Asn Met Ala Ser Gly Asn Val Ala Met Arg Phe Gly Ala Asn Gly Val Cys Lys Ser Ile Asn Thr Ala Cys Ser Ser Ser Asn Asp Ala Ile Gly Asp Ala Phe Arg Ser Ile Lys Phe Gly Phe Gln Asp Val Met Leu Val Gly Gly Thr G1u A1a Ser Ile Thr Pro Phe Ala Ile Ala Gly Phe Gln Ala Leu Thr Ala Leu Ser Thr Thr Gl_u Asp Pro Thr Arg Ala Ser Ile Pro Phe Asp Lys Asp Arg Asn Gly Phe Va1 Met Gly Glu Gly Ser Gly Met Leu Val Leu Glu Ser Leu Glu His Ala Glu Lys Arg Gly Ala Thr Ile Leu Ala Glu Val Val Gly Tyr Gly Asn Thr Cys Asp Ala Tyr His Met Thr Ser Pro His Pro Glu Gly Gln Gly Ala Ile Lys Ala Ile Lys Leu Ala Leu Glu Glu Ala Glu Ile Ser Pro G1u Gln Val Ala Tyr Val Asn Ala His Gly Thr Ser Thr Pro Ala Asn Glu Lys Gly Glu Ser Gly Ala Ile Val Ala Val Leu Gly Lys Glu Val Pro Val Ser Ser Thr Lys Ser Phe Thr Gly His Leu LeuGly AlaAlaGly AlaValGlu AlaIle ValThrIleGlu Ala Met ArgHis AsnPheVal ProMetThr AlaGly ThrSerGluVal 355 360~ 365 Ser Asp TyrIle GluAlaAsn ValValTyr GlyGln GlyLeuGluLys Glu Tle ProTyr AlaIleSer AsnThrPhe GlyPhe GlyGlyHisAsn ISAla Val LeuAla PheLysArg TrpGluAsn Arg <210> 200 <211> 359 <212> PRT

<213> Streptococcus pneumoniae <400> 200 2$ Met Asn Tyr AspGln LeuGlnVal ValGluAsp ArgTyrGlu Glu Ile Leu Gly Leu LeuSer AspProAsp ValValSer AspThrLys Arg Glu Phe Met Leu SerLys GluGluAla SerAsnArg AspThrVal Ile Glu Ala Tyr Glu TyrLys GlnValLeu GlnAsnIle ValAspAla Glu Arg Glu Met Lys GluSer GlyGlyAsp AlaAspLeu GluGluLeu Ala Ile 40 Lys Gln Leu LysAsp AlaLysAla GluLysGlu GluTyrGlu Glu Glu Lys Leu Lys Ile Leu Leu Leu Pro Lys Asp Pro Asn Asp Asp Lys Asn Ile IleLeuGlu IleArgGly AlaAlaGly GlyAspGlu AlaAla Leu Phe AlaGlyAsp LeuLeuThr MetTyrGln LysTyrAla GluAla Gln Gly TrpArgPhe GluValMet GluAlaSer MetAsnGly ValGly Gly SSPhe LysGluVal ValAlaMet ValSerGly GlnSerVal TyrSer Lys Leu LysTyrGlu SerGly AlaHisArgVal GlnArgVal ProValThr Glu SerGlnGly ArgVal HisThrSerThr AlaThrVal LeuValMet Pro GluValGlu GluVal GluTyrAspIle AspProLys AspLeuArg Val AspIleTyr HisAla SerGlyAlaGly GlyGlnAsn ValAsnLys 225 230 235 ' 240 Val AlaThrAla ValArg IleValHisLeu ProThrAsn IleLysVal Glu MetGlnGlu GluArg ThrGlnGlnLys AsnArgGlu LysAlaMet Lys IleIleArg AlaArg ValAlaAspHis PheAlaGln IleAlaGln Asp GluGlnAsp AlaGlu ArgLysSerThr IleGlyThr GlyAspArg Sex GluArgIle ArgThr TyrAsnPhePro GlnAsnArg ValThrAsp His ArgIleGly LeuThr LeuGlnLysLeu AspThrIle LeuSerGly Lys LeuAspGlu Va1Val AspAlaLeuVal LeuTyrAsp GlnThrGln Lys LeuGluGlu LeuAsn Lys <210> 201 <21l> 559 <212>.
PRT

<213>.Streptococcus pneumoniae <400> 201 Met Ala Thr LeuLysPro GluGluVal G1yValPhe ~AlaIleGly Tyr Gly Leu Glu IleGlyLys AsnThrTyr G1yIleGlu TyrGlnAsp Gly Glu Ile Ile ValAspAla GlyTleLys PheProGlu AspAspLeu Ile Leu Gly Asp TyrValIle ProAspTyr SerTyrIle ValAspAsn Ile SS

Ile Asp Val LysAlaVal LeuIleThr HisGlyHis GluAspHis Arg 65 70 75 gp Ile Gly Gly Ile Pro Phe Leu Leu Lys Gln Ala Asn Val Pro Ile Tyr Ala GlyPro LeuAlaLeu AlaLeuIle ArgGlyLys LeuGluGlu His Gly LeuLeu ArgAsnAla LysLeuTyr GluIleAsn HisAsnThr Glu 115 120 ' 125 Leu ThrPhe LysAsnLeu LysAlaThr PhePheArg ThrThrHis Ser Ile ProGlu ProLeuGly IleValIle HisThrPro GlnGlyLys Ile 145 150 155~ 160 Val CysThr GlyAspPhe LysPhe.Asp PheThrPro ValGlyGlu Pro Ala AspLeu HisArgMet AlaAlaLeu GlyGluGlu GlyValLeu Cys Leu LeuSer AspSerThr AsnAlaGlu ValProThr PheThrAsn Ser l95 200 205 Glu LysVal ValGlyGln SerIleMet LysIleIle GlnGlyIle Glu 210 215 . 220 Gly ArgIle IlePheAla SerPheAla SerAsnIle PheArgLeu Gln Gln AlaThr GluAlaAla ValLysThr GlyArgLys IleAlaVal Phe Gly ArgSer MetGlu~LysAlaTleVal AsnGlyIle AspLeuGly Tyr Ile LysAla ProLysGly ThrPheIle GluProAsn GluIleLys Asp Tyr ProAla GlyGluVal LeuIleLeu CysThrGly SerGlnGly Glu Pro MetAla AlaLeuSer ArgIleALa AsnGlyThr HisArgGln Val Gln LeuGln ProGlyAsp ThrValIle PheSerSer SerProIle Pro $0 Gly AsnThr ThrSerVal AsnLysLeu IleAsnIle IleSerGlu Ala Gly ValGlu ValIleHis GlyLysVal AsnAsnIle HisThrSer Gly 355 360' 365 His GlyGly GlnGlnGlu GlnLysLeu MetLeuCys LeuIleLys Pro Lys Tyr Phe Met Pro Val His Gly Glu Tyr Arg Met Gln Lys Val His Ala Gly Leu Ala Val Asp Thr Gly Val Glu Lys Asp Asn Ile Phe Ile 405 410 ~ 415 Met Ser Asn Gly Asp Val Leu Ala Leu Thr Ala Asp Ser Ala Arg Ile Ala Gly His Phe Asn Ala Gln Asp Ile Tyr Val Asp Gly Asn Arg Ile Gly GluIleGly AlaAlaVal LeuLysAsp ArgArgAsp LeuSerGlu Asp GlyValVal LeuAlaVal AlaThrVal AspPheLys SerGlnMet Ile LeuSerG'lyProAspIle LeuSerArg GlyPheVal TyrMetArg' 485 490 495.

Glu SerGlyAsp LeuIleArg GlnSerGln ArgIleLeu PheAsnAla 500 505~ 510 BileArgIleAla LeuLysAsn LysAspAla SerValGln SerValAsn Gly AlaIleVal AsnAlaIle ArgProPhe Leu.TyrGlu AsnThrGlu 530 ~ 535 540 Arg GluProIle IleIlePro MetIleLeu ThrProAsp GluGlu <210> 202 <211> 450 <212> PRT

<213> Streptococcus pneumoniae <400> 202 Met Ala ValGluGluLeu ArgValGln ProGlnAsp IleLeuAla Glu Glu Gln ValLeuGlyAla IlePheIle AspGluSer LysLeuVal Ser Phe Val GluTyrIleGlu SerArgAsp PhePheLys TyrAlaHis Arg Arg Leu PheGlnAlaMet ValAspLeu SerAspArg GlyAspAla Ile Ile Asp A1a Thr Thr Val Arg Thr Ile Leu Asp Asn Gln G1y Asp Leu Gln Asn Ile Gly Gly Leu Ser Tyr Leu Val Glu Ile Val Asn Ser Val Pro Thr Ser Ala Asn Ala Glu Tyr Tyr Ala Lys Ile Val Ala Glu Lys Ala Met Leu Arg Arg Leu Ile Ala Lys Leu Thr Glu Ser Val Asn Gln Ala Tyr Glu Ala Ser Gln Pro Ala Asp Glu Ile Ile Ala Gln Ala G1u 130 . 135 140 Lys Gly Leu Ile Asp Val Ser Glu Asn Ala Asn Arg Ser Gly Phe Lys IS Asn Tle Arg Asp Val Leu Asn Leu Asn Phe Gly Asn Leu Glu Ala Arg 165 l70 175 Ser Gln Gln Thr Thr Asp Tle Thr Gly hle Ala Thr Gly Tyr Arg Asp Leu Asp His Met Thr Thr Gly Leu His Glu Glu Glu Leu Ile Ile Leu A1a Ala Arg Pro Ala Val Gly Lys Thr Ala Phe Ala Leu Asn Ile Ala Gln Asn Ile Gly Thr Lys Leu Asp Lys Thr Val Ala Ile Phe Ser Leu Glu Met Gly Ala Glu Ser Leu Val Asp Arg Met Leu Ala Ala Glu Gly 245 ~ 250 '255 Leu Val Glu Ser His Ser Ile Arg Thr Gly Gln Leu Thr Asp Glu Glu Trp Gln Lys Tyr Thr Ile Ala Gln Gly Asn Leu Ala Asn Ala Ser Ile Tyr Ile Asp Asp Thr Pro Gly Ile Arg Ile Thr Glu Ile Arg Ser Arg Ser Arg Lys Leu Ala Gln Glu Thr Gly Asn Leu Gly Leu Ile Val Ile Asp Tyr Leu Gln Leu Ile Thr Gly Thr Gly Arg Glu Asn Arg G1n Gln Glu Val Ser Glu Ile Ser Arg Gln Leu Lys Ile Leu Ala Lys Glu Leu Lys Val Pro Val Ile Ala Leu Ser Gln Leu Ser Arg Gly Val Glu Gln 355 360 365 ' Arg Gln Asp Lys Arg Pro Val Leu Ser Asp Ile Arg Glu Ser Gly Ser Ile Glu Gln Asp Ala Asp Ile Val Ala Phe Leu Tyr Arg Asp Asp Tyr Tyr Glu Arg Gly Gly Glu Glu Glu Glu Gly Ile Pro Asn Asn Lys Val S
Glu Val Ile Ile Glu Lys Asn Arg Ser Gly Ala Arg Gly Thr Val Glu Leu Ile Val Gln Lys Glu Tyr Asn Lys Phe Ser Ser Ile Ser Lys Arg Glu Ala <210> 203 <211> 699 <212> PRT
<213> Streptococcus pneumoniae <400> 203 Met Ala Thr Ala Thr Lys Lys Lys Lys Ser Thr Val Lys Lys Asn Leu 1 5 , 10 15 2$ Val Ile Val Glu Ser Pro Ala Lys Ala Lys Thr Ile Glu Lys Tyr Leu Gly Arg Asn Tyr Lys Val Leu Ala Ser Val Gly His Ile Arg Asp Leu Lys Lys Ser Ser Met Ser Val Asp Ile Glu Asn Asn Tyr Glu Pro Gln Tyr IleAsn IleArgG1y LysGlyPro LeuIleAsnAsp LeuLys Lys Glu AlaLys LysAlaAsn LysValPhe LeuAlaSerAsp ProAsp Arg Glu GlyGlu AlaIleSer TrpHisLeu AlaHisIleLeu AsnLeu Asp Glu AsnAsp AlaAsnArg Va1ValPhe AsnGluIleThr LysAsp Ala 115 120' l25 Val LysAsn AlaPheLys GluProArg LysIleAspMet AspLeu Val Asp AlaGln GlnAlaArg ArgIleLeu AspArgLeuVal GlyTyr Ser Ile SerPro IleLeuTrp LysLysVal LysLysGlyLeu SerAla Gly 5$ Arg ValGln SerIleAla LeuLysLeu IleIleAspArg GluAsn Glu Ile Asn Ala Phe Gln Pro Glu Glu Tyr Trp Thr Val Asp Ala Val Phe 195 200 ~ 205 Lys Lys Gly Thr Lys Gln Phe His Ala Ser Phe Tyr Gly Val Asp Gly Lys Lys Met Lys Leu Thr Ser Asn Asn Glu Val Lys Glu Val Leu Ser Arg Leu Thr Ser Lys Asp Phe Ser Val Asp Gln Val Asp Lys Lys Glu Arg Lys Arg Asn Ala Pro Leu Pro Tyr Thr Thr Ser Ser Met Gln Met IS
Asp Ala Ala Asn Lys Ile Asn Phe Arg Thr Arg Lys Thr Met Met Val Ala Gln G1n Leu Tyr Glu Gly Ile Asn Ile Gly Ser G.ly Val Gln Gly Leu Ile Thr Tyr Met Arg Thr Asp Ser Thr Arg Ile Ser Pro Val Ala Gln Asn Glu Ala Ala Ser Phe Ile Thr Asp Arg Phe Gly Ser Lys Tyr Ser Lys His Gly Ser Lys Val Lys Asn Ala Ser Gly Ala Gln Asp Ala His Glu Ala Ile Arg Pro Ser Ser Val Phe Asn Thr Pro Glu Ser Ile Ala Lys Tyr Leu Asp Lys Asp Gln Leu Lys Leu Tyr Thr Leu Ile Trp Asn Arg Phe Val Ala Ser Gln Met Thr Ala~Ala Val Phe Asp Thr Met 385 390 , 395 400 Ala Val Lys Leu Ser Gln Lys Gly Val Gln Phe Ala Ala Asn Gly Ser Gln Val Lys Phe Asp Gly Tyr Leu Ala Ile Tyr Asn Asp Ser Asp Lys Asn Lys Met Leu Pro Asp Met Val Val Gly Asp Val Val Lys Gln Val Asn Ser Lys Pro Glu Gln His Phe Thr Gln Pro Pro Ala Arg Tyr Ser $0 450 ~ 455 460 Glu Ala Thr Leu Ile Lys Thr Leu Glu Glu Asn Gly Val Gly Arg Pro 465 470 475 ' 480 Ser Thr Tyr Ala Pro Thr Ile Glu Thr Ile Gln Lys Arg Tyr Tyr Val Arg Leu Ala Ala Lys Arg Phe Glu Pro Thr Glu Leu Gly Glu Ile Val sn Lys Leu Ile Val Glu Tyr Phe Pro Asp Ile Val Asn Val Thr Phe Thr Ala Glu Met Glu Gly Lys Leu Asp Asp Val Glu Val Gly Lys G1u Gln TrpArgArg ValIle AspAlaPhe TyrLysPro PheSerLys Glu Val AlaLysAla GluGlu GluMetGlu LysIleGln IleLysAsp Glu Pro AlaGlyPhe AspCys GluValCys GlySerPro MetValIle Lys Leu GlyArgPhe GlyLys PheTyrAla CysSerAsn PheProAsp Cys Arg HisThrGln AlaIle ValLysGlu IleGlyVal GluCysPro Ser Cys HisGlnGly GlnIle TleGluArg LysThrLys ArgAsnArg Leu Phe TyrGlyCys AsnArg TyrProGlu CysGluPhe ThrSerTrp Asp Lys ProValGly ArgAsp Cys,ProLys CysGlyAsn PheLeuMet Glu Lys LysValArg GlyGly GlyLysGln ValValCys SerLysGly Asp 675 680 ~ 685 Tyr Glu.GluGlu LysMet AlaLeuCys GlnLeu <210> 204 <211> 326 <2l2> PRT

45<213> Streptococcus pneumoniae <400> 204 Met Phe Ser IleSerAla GlyIleVal ThrPheLeu LeuThrLeu Ile 1 5 ' 10 15 Val Gly Pro AlaPheIle GlnPheTyr ArgLysAla Gln,IleThr Ile Gly Gln Met HisGluAsp ValLysGln HisGlnAla LysAlaGly Gln Thr Pro Met GlyGlyLeu ValPheLeu IleThrSer ValLeuVal Thr Ala Phe Phe Phe Ala Leu Phe Ser Ser Gln Phe Ser Asn Asn Val Gly Met Tle LeuPheIle LeuValLeu TyrGlyLeu ValGlyPhe LeuAsp Asp Phe LeuLysVal PheArgLys IleAsnGlu GlyLeuAsn ProLys 100 l05 1l0 Gln Lys LeuAlaLeu GlnLeuLeu GlyGlyVal IlePheTyr LeuPhe IS Tyr Glu ArgGlyGly AspMetLeu SerValPhe GlyTyrGln ValHis Leu Gly IlePheTyr IleVa1Phe AlaLeuPhe TrpLeuVal GlyPhe Ser Asn AlaValAsn LeuThrAsp GlyValAsp GlyLeuAla SerIle Ser Val ValIleSer LeuSerAla TyrGlyVal IleAlaTyr ValGln Gly Gln MetAspIle LeuLeuVal IleLeuAla MetIleGly GlyLeu Leu Ser PhePheIle PheAsnHis LysProAla LysIlePhe MetGly 210 215 ' 220 Asp Val GlySerLeu AlaLeuGly GlyMetLeu AlaAlaIle SerMet Ala Leu HisGlnGlu TrpThrLeu LeuIleIle GlyIleVal TyrVal Phe Glu ThrThrSer ValMetMet GlnValSer TyrPheLys LeuThr Gly Gly LysArgIle PheArgMet ThrProVal HisHisHis PheGlu Leu Gly GlyLeuSer GlyLysGly AsnProTrp SerGluTrp LysVal Asp Phe PhePheTrp GlyValGly LeuLeuAla SerLeuLeu ThrLeu .

Ala Ile LeuTyrLeu Met SS <210> 205 <211> 693 <212> PRT

<213> Streptococcus pneumoniae <400> 205 Met Ala Arg Glu Phe Ser Leu Glu Lys Thr Arg Asn Ile Gly Ile Met Ala His Val Asp Ala Gly.Lys Thr Thr Thr Thr Glu Arg Ile Leu Tyr Tyr Thr Gly Lys Ile His Lys Ile Gly Glu Thr His Glu Gly Ala Ser 35 40 45 .
Gln Met Asp Trp Met Glu Gln Glu Gln Glu Arg Gly Ile Thr Ile Thr 50 55 . 60 Ser Ala Ala Thr Thr Ala Gln Trp Asn Asn His Arg Val Asn Ile Ile Asp Thr Pro Gly His Val Asp Phe Thr Tle Glu Val Gln Arg Ser Leu Arg Val Leu Asp Gly Ala Val Thr Val Leu Asp Ser Gln Ser Gly Val S Glu Pro Gln Thr Glu Thr Val Trp Arg Gln Ala Thr Glu Tyr Gly Val 115 ~ 120 125 Pro Arg Ile Val Phe Ala Asn Lys Met Asp Lys Ile Gly Ala Asp Phe Leu Tyr Ser Val Ser Thr Leu His Asp Arg Leu Gln Ala Asn A1a His Pro Ile Gln Leu Pro I1e Gly Ser Glu Asp Asp Phe Arg Gly Ile Ile Asp Leu Ile Lys Met Lys Ala Glu Ile Tyr Thr Asn Asp Leu Gly Thr Asp Ile Leu Glu Glu Asp Ile Pro Ala Glu Tyr Leu Asp Gln Ala Gln Glu Tyr Arg Glu Lys Leu Ile Glu Ala Val Ala Glu Thr Asp Glu Glu Leu Met Met Lys Tyr Leu Glu Gly Glu Glu Ile Thr Asn Glu Glu Leu Lys Ala Gly Ile Arg Lys Ala Thr Ile Asn Val Glu Phe Phe Pro Val Leu Cys Gly Ser Ala Phe Lys Asn Lys Gly Val Gln Leu Met Leu Asp 260 265 270 .
Ala Val Ile Asp Tyr Leu Pro Ser Pro Leu Asp Ile Pro Ala Ile Lys Gly Ile Asn Pro Asp Thr Asp Ala Glu Glu Ile Arg Pro Ala Ser Asp Glu Glu Pro Phe Ala Ala Leu Ala Phe Lys Ile Met Thr Asp Pro Phe Val Gly Arg Leu Thr Phe Phe Arg Val Tyr Ser Gly Val Leu Gln Ser Gly Ser Tyr Va1 Leu Asn Thr Ser Lys Gly Lys Arg Glu Arg Ile Gly Arg Ile Leu Gln Met His Ala Asn Ser Arg Gln Glu Ile Asp Thr Val Tyr Ser Gly Asp Ile Ala Ala Ala Val Gly Leu Lys Asp Thr Thr Thr Gly Asp Ser Leu Thr Asp Glu Lys Ala Lys Ile Ile Leu Glu Ser Ile Asn~Val Pro Glu Pro Val Ile Gln Leu Met Val Glu Pro Lys Ser Lys 405 410 ' 415 Ala Asp Gln Asp Lys Met Gly Tle Ala Leu Gln Lys Leu Ala Glu Glu Asp Pro Thr Phe.Arg Val Glu Thr Asn Val Glu Thr Gly G1u Thr Val Ile Ser Gly Met Gly Glu Leu His Leu Asp Val Leu Val Asp Arg Met Arg Arg Glu Phe Lys Val Glu Ala Asn Val Gly Ala Pro Gln Val Ser Tyr Arg Glu Thr Phe Arg Ala Ser Thr Gln Ala Arg Gly Phe Phe Lys Arg Gln Ser Gly Gly Lys Gly Gln Phe Gly Asp Val Trp Ile Glu Phe Thr Pro Asn Glu Glu Gly Lys Gly Phe Glu Phe Glu Asn Ala Ile Val Gly Gly Va1 Val Pro Arg Glu Phe Ile Pro Ala Val Glu Lys Gly Leu Val Glu Ser Met Ala Asn Gly Val Leu Ala Gly Tyr Pro Met Val Asp Val Lys Ala Lys Leu Tyr Asp Gly Ser Tyr His Asp Val Asp Ser Ser SS Glu Thr Ala Phe Lys Ile Ala Ala Ser Leu Ser Leu Lys Glu Ala Ala Lys Ser AlaGlnPro AlaIleLeu GluProMet MetLeuVal ThrIle Thr Val ProGluGlu AsnLeuGly AspValMet GlyHisVal ThrAla Arg Arg GlyArgVal AspGlyMet GluAlaHis GlyAsnSer GlnIle 1~ Val Arg AlaTyrVal ProLeuAla GluMetPhe GlyTyrAla ThrVal Leu Arg SerAlaSer GlnGlyArg GlyThrPhe MetMetVal PheAsp His Tyr GluAspVal ProLysSer ValGlnGlu GluIleIle LysLys Asn Lys GlyGluAsp <210>

<211>

2$ <212>
PRT

<213> pneumoniae Streptococcus <400>

Met Pro TyrAsn IleProPhe SerProPro AspIleThr GluAla Asn Glu Ile GluVal AlaAspThr LeuArgSer GlyTrpIle ThrThr Ala 3$ Gly Pro ThrLys GluLeuGlu ArgArgLeu SerLeuTyr ThrGln Lys Thr Pro ThrVal CysLeuAsn SerAlaThr AlaAlaLeu GluLeu Lys Ile Leu ValLeu GluValGly ProGlyAsp GluValIle ValPro Arg Ala Met .TyrThr AlaSerCys SerValIle ThrHisVal GlyAla Thr Thr Pro MetVal AspIleGln AlaAspThr PheGluMet AspTyr Val ~ Asp Leu GluGln AlaIleThr GluLysThr LysValIle IlePro Leu l15 120 225 Val Glu AlaGly IleValCys AspTyrAsp ArgLeuPhe GlnVal Leu SS

Val Glu LysArg AspPhePhe ThrAlaSer SerLysTrp GlnLys Lys Ala Phe Asn Arg Ile Va1 Ile Val Ser Asp Ser Ala His Ala Leu Gly $ Ser Thr Tyr Lys Gly Gln Pro Ser Gly Ser Ile Ala Asp Phe Thr Ser Phe Ser Phe His Ala Val Lys Asn Phe Thr Thr Ala Glu Gly Gly Ser Ala Thr Trp Lys Ala.Asn Pro Val Ile Asp Asp Glu Glu Met Tyr Lys 210 . 215 220 Glu Phe Gln Ile Leu Ser Leu His Gly Gln Thr Lys Asp Ala Leu Ala Lys Met Gln Leu Gly Ser Trp Glu Tyr Asp I1e Val Thr Pro Ala Tyr Lys Cys Asn Met Thr Asp Ile Met Ala Ser Leu Gly Leu Val Gln Leu Asp Arg Tyr Pro Ser Leu Leu Gln Arg Arg Lys Asp Ile Val Asp Arg Tyr Asp Ser Gly Phe Ala Gly Ser Arg Ile His Pro Leu Ala His Lys Thr Glu Thr Val Glu Ser Ser Arg His Leu Tyr Ile Thr Arg Val Glu 305 . 310 315 320 Gly Ala Ser Leu Glu G1u Arg Ser Leu Tle Ile Gln Glu Leu Ala Lys 3$ Ala Gly Ile Ala Ser Asn Val His Tyr Lys Pro Leu Pro Leu Leu Thr Ala Tyr Lys Asn Leu Gly Phe Asp Met Thr Asn Tyr Pro Lys Ala Tyr Ala Phe Phe-Glu Asn Glu Ile Thr Leu Pro Leu His Thr Lys Leu Ser 370 . 375 380 Asp Glu Glu Val Asp Tyr Ile Ile Glu Thr Phe Lys Thr Val Ser G1u Lys Val Leu Thr Leu Ser Lys Lys <210> 207 <211> 325 <212> PRT
<213> Streptococcus pneumoniae <400> 207 Met Thr Glu Pro Asp Phe Trp Asn Asp Asn Ile Ala Ala Gln Lys Thr Ser Gln Glu Leu Asn Va1 Phe Lys Asn Thr Tyr Asn Thr Phe His Lys Met Glu Glu Leu Gln Asp Glu Val Glu Ile Leu Leu Asp Phe Leu Ala Glu Asp Glu Ser Val His Asp Glu Leu Va1 Ala Gln Leu Ala Glu Leu 50 ~ 55 60 Asp Lys IleMetThr SerTyrGlu MetThrLeu LeuLeuSer GluPro IS Tyr Asp HisAsnAsn AlaIleLeu GluIleHis ProGlySer GlyGly Thr Glu AlaGlnAsp TrpGlyAsp MetLeuLeu ArgMet.TyrThrArg ' Tyr Gly AsnAlaLys GlyPheLys ValGluVal LeuAspTyr GlnAla Gly Asp GluAlaGly IleLysSer ValThrLeu SerPheGlu GlyPro Asn Ala TyrGlyLeu LeuLysSer GluMetGly ValHisArg LeuVal Arg Ile SerProPhe AspSerAla LysArgArg HisThrSer PheThr Ser Val GluValMet ProGluLeu AspAspThr IleGluVal GluIle Arg G1u AspAspIle LysMetAsp ThrPheArg SerGlyGly AlaGly Gly Gln AsnValAsn LysValSer ThrGlyVal ArgLeuThr HisIle Pro Thr GlyIleVal ValGlnSer ThrValAsp ArgThrGln TyrGly 5 Asn Arg AspArgAla MetLysMet LeuGlnAla LysLeuTyr GlnMet Glu Gln GluLysLys AlaAlaGlu ValAspSer LeuLysGly GluLys Lys Glu IleThrTrp GlySerGln IleArgSer TyrValPhe ThrPro Tyr Thr MetValLys AspHisArg ThrSerPhe GluVa1Ala GlnVal Asp Lys ValMetAsp GlyAspLeu AspGlyPhe IleAspAla TyrLeu Lys Trp Arg Ile Ser <210> 208 <211> 249 <212> PRT
<213> Streptococcus pneumoniae <400> 208 Met Phe Tyr Thr Tyr Leu Arg Gly Leu Val Val Leu Leu Leu Trp Ser Ile Asn Gly Asn Ala His Tyr His Asn Thr Asp Lys Ile Pro Asn Gln Asp Glu Asn Tyr I1e Leu Val Ala Pro His Arg Thr Trp Trp Asp Pro Val Tyr Met Ala Phe Ala Thr Lys Pro Lys Gln Phe Ile Phe Met Ala 2S Lys Lys Glu Leu Phe Thr Asn Arg Tle Phe Gly Trp Trp Ile Arg Met Cys Gly Ala Phe Pro Ile Asp Arg Glu Asn Pro Ser Al.a Ser Ala Ile Lys Tyr Pro Ile Asn Val Leu Lys Lys Ser Asp Arg Ser Leu Ile Met Phe Pro Ser Gly Ser Arg His.Ser Asn Asp Val Lys Gly Gly Ala Ala Leu Ile Ala Lys Met Ala Lys Val Arg Ile Met Pro Val Thr Tyr Thr Gly Pro Met Thr Leu Lys Gly Leu Ile Ser Arg Glu Arg Va_1 Asp Met Asn Phe Gly Asn Pro Ile Asp Ile Ser Asp Ile Lys Lys Met Asn Asp Glu Gly Ile Glu Thr Val Ala Asn Arg Ile Gln Thr G1u Phe Gln Arg Leu Asp Glu Glu Thr Lys Gln Trp His Asn Asp Lys Lys Pro Asn Pro Leu Trp Trp Phe Ile Arg I1e Pro Ala Leu Ile Leu Ala Ile Ile Leu Ala Ile Leu Thr Ile Ile Phe Ser Phe Ile Ala Ser Phe Ile Trp Asn Pro Asp Lys Lys Arg Glu Glu Leu Ala <210> 209 <211> 1033 <212> PRT
<213> Streptococcus pneumoniae <400> 209 Met Ile Ala Gln Leu Asp Thr Lys Thr Val Tyr Ser Phe Met Glu Ser Val Ile Ser Ile Glu Lys Tyr Val Arg Ala Ala Lys Glu Tyr Gly Tyr 1$ 20 25 30 Thr His Leu Ala Met Met Asp Ile Asp Asn Leu Tyr Gly Ala Phe Asp Phe Leu Glu Ile Thr Lys Lys Tyr Gly Ile His Pro Leu Leu Gly Leu Glu Met Thr Val Phe Val Asp Asp Gln Gly Val Asn Leu Arg Phe Leu Ala Leu Ser Ser Val Gly Tyr Gln Gln Leu Met Lys Leu Ser Thr Ala Lys Met Gln Gly Glu Lys Thr Trp Ser Va1 Leu Ser Gln Tyr Leu Glu Asp Ile Ala Val Ile Val Pro Tyr Phe Asp Arg Val Glu Ser Leu Glu 1l5 120 125 Leu Gly Cys Asp Tyr Tyr Ile Gly Val Tyr Pro Glu Thr Leu Ala Ser Glu Phe His His Pro Ile Leu Pro Leu Tyr Arg Val Asn Ala Phe Glu Ser Arg Asp Arg Glu Val Leu Gln Val Leu Thr Ala Ile Lys Glu Asn Leu Pro Leu Arg Glu Val Pro Leu Arg Ser Arg Gln Asp Val Phe Ile Ser Ala Ser Ser Leu Glu Lys Leu Phe Gln Glu Arg Phe Pro Gln Ala Leu Asp Asn Leu Glu Lys Leu Ile Ser Gly Ile Ser Tyr Asp Leu Asp Thr Ser Leu Lys Leu Pro Arg Phe Asn Pro Ala Arg Pro Ala Val Glu SS
Glu Leu Arg Glu Arg Ala Glu Leu Gly Leu Val Gln Lys Gly Leu Thr Ser Lys Glu Tyr Gln Asp Arg Leu Asp Gln Glu Leu Ser Val Ile His 260 . 265 270 Asp Met Gly Phe Asp Asp Tyr Phe Leu Val Val Trp Asp Leu Leu Arg Phe Gly Arg Ser Asn Gly Tyr Tyr Met Gly Met Gly Arg G1y Ser Ala Val Gly Ser Leu Val Ser Tyr Ala Leu Asp Ile Thr Gly Ile Asp Pro Val Glu Lys Asn Leu Ile Phe Glu Arg Phe Leu Asn Arg Glu Arg Tyr Thr Met Pro Asp Ile Asp Tle Asp Ile Pro Asp Ile Tyr Arg Pro Asp ~0 Phe Ile Arg Tyr Val Gly Asn Lys Tyr Gly Ser Lys His Ala Ala Gln Ile Val Thr Phe Ser Thr Phe Gly Ala Lys Gln Ala Leu Arg Asp Val 370 . 375 380 Leu Lys Arg Phe Gly Val Pro Glu Tyr Glu Leu Ser Ala Ile Thr Lys Lys Ile Ser Phe Arg Asp Asn Leu Lys Ser Ala Tyr Glu Gly Asn Leu 'S
Gln Phe Arg Gln Gln Ile Asn Ser Lys Leu Glu Tyr Gln Lys Ala Phe Glu~Ile Ala Cys Lys 21e Glu Gly Tyr Pro Arg Gln Thr Ser Val His Ala Ala Gly Val Val Ile Ser Asp Gln Asp Leu Thr Asn Tyr Ile Pro Leu Lys Tyr Gly Asp Glu Ile Pro Leu Thr Gln Tyr Asp Ala His Gly Val Glu Ala Ser Gly Leu Leu Lys Met Asp Phe Leu Gly Leu Arg Asn 4$ 485 490 495 Leu Thr Phe Val Gln Lys Met Gln Glu Leu Leu Ala Glu Ile Glu Gly Ile His Leu Lys Ile Glu Glu Ile Asp Leu Glu Asp Lys Glu Thr Leu Asp Leu Phe Ala Ser Gly Asn Thr Lys Gly Ile Phe Gln Phe Glu Glh Pro Gly Ala Ile Arg Leu Leu Lys Arg.Val Gln Pro Val Cys Phe Glu Asp Val Val Ala Thr Thr Ser Leu Asn Arg Pro Gly Ala Ser Asp Tyr S Ile Asn Asn Phe Val Ala Arg Lys His Gly Gln Glu Glu Val Thr Val Leu Asp Pro Val Leu Glu Asp Ile Leu Ala Pro Thr Tyr Gly Ile Met Leu Tyr Gln Glu Gln Val Met Gln Val Ala Gln Arg Phe Ala Gly Phe Ser Leu Gly Lys Ala Asp Ile Leu Arg Arg Ala Met Gly Lys Lys Asp Ala Ser Ala Met His Glu Met Arg Ala Ser Phe Ile Gln Gly Ser Leu Glu Ala Gly His Thr Val Glu Lys Ala Glu Gln Val Phe Asp Val Met Glu Lys Phe Ala Gly Tyr Gly Phe Asn Arg Ser His Ala Tyr Ala Tyr 675 ~ 680 685 Ser Ala Leu Ala Phe Gln Leu Ala Tyr Phe Lys Thr His Tyr Pro Ala Ile Phe Tyr Gln Ile Met Leu Asn Ser Ala Asn Ser Asp Tyr Leu Tle Asp Ala Leu Glu Ala Gly Phe Glu Val Ala Pro Leu Ser Ile Asn Thr 5 Ile Pro Tyr His~Asp Lys Ile Ala Asn Lys Ala Ile Tyr Leu Gly Leu Lys Ser Ile Lys Gly Val Ser Asn Asp.Leu A1a Leu Trp Il,e I1e G1u 755 760 ~ 765 His Arg Pro Tyr Ser Asn Ile Glu Asp Phe I1e Ala Lys Leu Pro Glu Asn Tyr Leu Lys Leu Hro Leu Leu Glu Pro Leu Val Lys Val Gly Leu Phe Asp Ser Phe Glu Lys Asn Arg Gln Lys Val Phe Asn Asn Leu Ala $0 Asn.Leu Phe Glu Phe Val Lys Glu Leu Gly Ser Leu Phe Gly Asp Ala I1e Tyr Ser Trp Gln Glu Ser Glu Asp Trp Thr Glu Gln Glu Lys Phe Tyr Met Glu Gln Glu Leu Leu Gly Ile Gly Val Ser Lys His Pro Leu Gln AlaIleAlaSerLys AlaIle TyrProIleThr ProIle GlyAsn Leu SerGluAsnSerTyr AlaIle IleLeuValGlu ValGln LysIle 885 890 . 895 Lys ValIleArgThrLys LysGly GluAsnMetAla PheLeu GlnA1a Asp AspSerLysLysLys LeuAsp ValThrLeuPhe SerAsp~LeuTyr Arg GlnValGlyGlnGl_uIleLys GluGlyAlaPhe TyrTyr ValLys Gly LysIleGlnSerArg AspGly ArgLeuGlnMet IleAla GlnGlu Ile ArgGluAlaValAla GluArg PheTrpIleGln ValLys AsnHis 965~ 970 975 Glu SerAspGlnGluIle SerArg IleLeuGluGln PheLys GlyPro Ile ProValIleIleArg TyrGlu GluGluGlnLys ThrIle ValSer Pro HisHisPheValAla LysSer ~AsnGluLeuGlu GluLys LeuAsn Glu IleValMetLysThr IleTyr Arg <210> 210 <211> 306 <212> PRT

<213> Streptococcus pneumoniae <400> 210 Met Thr GluPhe LeuHis.PheGluLysIle SerArgGln ThrTrp Asn Gln Ser HisArg LysThrThr ProProLeu ThrGluGlu GluLeu Leu Glu Ser LysSer PheAsnAsp GlnTleSer LeuGlnAsp ValThr Ile Asp Ile LeuPro LeuAlaHis LeuIleGln IleTyrLys ArgThr Tyr Lys Glu LeuAla PheSerLys GlyIlePhe LeuGlnArg GluSer Asp Lys Ser ProPhe IleIleGly ValSerGly SerValAla ValGly Gln Lys Ser ThrThrSer ArgLeuLeu GlnIleLeu LeuSerArg ThrPhe Thr Asp AlaThrVal GluLeuVal ThrThrAsp GlyPheLeu TyrPro 115 120 l25 Asn Gln ThrLeuIle GluGlnGly IleLeuAsn ArgLysGly PhePro 130 135 . ~ 140 Glu Ser TyrAspMet GluAlaLeu LeuAsnPhe LeuAspArg IleLys IS Asn Gly GlnAspVal AspIlePro ValTyrSer HisGluVal TyrAsp Ile Val ProLysLys LysGlnSer ValLysAla AlaAspPhe ValIle Val Glu GlyIleAsn ValPheGln Asn.ProGln AsnAspArg LeuTyr Ile Thr AspPhePhe AspPheSer IleTyrVal AspAlaGly ValAsp Asp Ile GluSerTrp TyrLeuAsp ArgPheLeu LysMetLeu SerLeu Ala Gln AsnAspPro AspSerTyr TyrTyrArg PheThrGln MetPro 245 ' 250 255 Ile Gly GluValGlu SerPheAla HisGlnVal TrpThrSer IleAsn Leu Thr AsnLeuGln AsnTyrIle GluProThr ArgAsnArg AlaGlu Val Ile LeuHisLys SerLysAsn HisGluTle AspGluIle TyrLeu 290 ~ 295 300 Lys Lys <210> 211 <211> 246 <212> PRT
<213> Streptococcus pneumoniae <400> 211 Met Glu Ile Ser Leu Leu Thr Asp Val 'Gly Gln Lys Arg Thr Asn Asn 5$ Gln Asp Tyr Val Asn His Tyr Val Asn Arg Ala Gly Arg Thr Met Ile Ile Leu Ala Asp Gly Met Gly Gly His Arg Ala Gly Asn Ile Ala Ser Glu -MetAlaVal ThrAspLeu GlyValAla TrpValAsp ThrGlnIle Asp ThrValAsn GluValArg GluTrpPhe A1aHisTyr LeuGluIle 10Glu AsnGlnLys IleHisGln LeuGlyGln AspGluAla TyrArgGly Met GlyThrThr LeuGluVal LeuAlaIle IleAspAsn GlnAlaIle 100 105 . 110 Tyr AlaHisIle GlyAspSer ArgIleGly LeuIleArg GlyGluGlu Tyr HisGlnLeu ThrSerAsp HisSerLeu ValAsnGlu LeuLeuLys Ala GlyGlnLeu ThrProGlu GluAlaGlu AlaHisPro GlnLysAsn 25Ile I1eThrGln SexIleGly GlnLysAsp GluIleGln ProAspPhe Gly ThrValT1e LeuGluSer GlyAspTyr.LeuLeuLeu AsnSerAsp Gly LeuThrAsn MetIleSer G1ySerGlu IleArgAsp IleValThr Ser AspIlePro LeuAlaAsp LysThrGlu ThrLeuVal ArgPheAla Asn AsnAlaGly GlyLeuAsp AsnIleThr ValAlaLeu ValSerMet 40Asn GluGluAsp GluGlu <220>

4S<211 >

<212>
PRT

<213> pneumoni ae Streptococcus <400>

5~Met ThrIleGln MetLysAsn ThrGlyLys ArgIleAsp LeuIleAla Asn Arg Lys Pro Gln Ser Gln Arg Val Leu Tyr Glu Leu Arg Asp Arg Leu Lys Arg Asn Gln Phe Ile Leu Asn Asp Thr Asn Pro Asp Ile Val Ile Ser Ile Gly Gly Asp Gly Met Leu Leu Ser Ala Phe His Lys Tyr Glu Asn Gln Leu Asp Lys Val Arg Phe Ile Gly Leu His Thr Gly His Leu Gly Phe Tyr Thr Asp Tyr Arg Asp Phe Glu Leu Asp Lys Leu Val Thr Asn Leu Gln Leu Asp Thr Gly Ala Arg Val Ser Tyr Pro Val Leu 100 105 . 110 Asn Val Lys Val Phe Leu Glu Asn Gly Glu Val Lys'Ile Phe Arg A1a Leu Asn Glu Ala Ser Ile Arg Arg Ser Asp Arg Thr Met Val Ala Asp Ile Val Ile Asn Gly Val Pro Phe Glu Arg Phe Arg Gly Asp Gly Leu Thr Val Ser Thr Pro Thr Gly Ser Thr Ala Tyr Asn Lys Ser Leu Gly 25' Gly Ala Val Leu His Pro Thr Ile Glu Ala Leu Gln Leu Thr Glu Ile Ala Ser Leu Asn Asn Arg Val Tyr Arg Thr Leu Gly Ser Ser Ile Ile Val Pro Lys Lys Asp Lys Ile Glu Leu Ile Pro Thr Arg Asn Asp Tyr 35 His Thr Ile Ser Val Asp Asn Ser Val Tyr Ser Phe Arg Asn Ile Glu Arg Ile Glu Tyr Gln Ile Asp His His Lys Ile His Phe Val Ala Thr Pro Ser His Thr Ser Phe Trp Asn Arg Val Lys Asp A1a Phe Ile Gly Glu Val Asp Glu <210> 213 <211> 540 $0 <212> PRT
<213> Streptococcus pneumoniae <400> 2l3 Met Ser Lys Glu Ile Lys Phe Ser Ser Asp Ala Arg Ser Ala Met Val Arg Gly Val Asp Ile Leu Ala Asp Thr Val Lys Val Thr Leu Gly Pro Lys Gly Arg Asn Val Val Leu Glu Lys Ser Phe Gly Ser Pro Leu Ile Thr Asn Asp Gly Val Thr Ile Ala Lys G1u Ile Glu Leu Glu Asp His Phe Glu Asn Met Gly Ala Lys Leu Va1 Ser Glu Val Ala Ser Lys Thr Asn Asp Ile Ala Gly Asp Gly Thr Thr Thr Ala Thr Val Leu Thr Gln 1$ Ala Ile Val Arg Glu Gly Ile Lys Asn Val Thr Ala Gly Ala Asn Pro Ile Gly Ile Arg Arg Gly Ile Glu Thr Ala Val Ala Ala Ala Val Glu Ala Leu Lys Asn Asn Ala Ile Pro Val Ala Asn Lys Glu Ala Ile Ala 130 135 l40 Gln Val Ala Ala Val Ser Ser Arg Ser Glu Lys Val Gly Glu Tyr Ile 2S 145 150 155 160 _ Ser Glu Ala Met Glu Lys Val Gly Lys Asp Gly Val Ile Thr Ile Glu Glu Ser Arg Gly Met Glu Thr Glu Leu Glu Val Val Glu Gly Met Gln Phe Asp Arg Gly Tyr Leu Ser Gln Tyr Met Val Thr Asp Ser Glu Lys l95 200 205 Met Val Ala Asp Leu Glu Asn Pro Tyr I1e Leu Ile Thr Asp Lys Lys Ile Ser Asn Ile Gln Glu Ile Leu Pro Leu Leu Glu Ser Ile Leu Gln Ser Asn Arg Pro Leu Leu Ile Tle Ala Asp Asp Val Asp Gly Glu Ala Leu Pro Thr Leu Val Leu Asn Lys Ile Arg Gly Thr,Phe Asn Val Val Aha Val Lys Ala Pro Gly Phe Gly Asp Arg Arg Lys Ala Met Leu G1u Asp Ile Ala Ile Leu Thr Gly Gly Thr Val Ile Thr Glu Asp Le.u Gly Leu Glu Leu Lys Asp Ala Thr Tle Glu Ala Leu Gly Gln A_la Ala Arg Val Thr Val Asp Lys Asp Ser Thr Val Ile Val Glu Gly Ala Gly Asn 325 330 ~ 335 Pro Glu Ala Ile Ser His Arg Val Ala Val Tle Lys Ser Gln Ile Glu Thr.Thr Thr Ser Glu Phe Asp Arg Glu Lys Leu Gln Glu Arg Leu Ala Lys Leu Ser Gly Gly Val Ala Val I1e Lys Val Gly Ala Ala Thr Glu Thr Glu Leu Lys Glu Met Lys Leu Arg Ile Glu Asp Ala Leu Asn A1a 385 ~ 390 ~3~95 400 Thr Arg Ala Ala Val Glu Glu Gly Ile Val Ala Gly Gly Gly Thr Ala Leu Ala Asn Val Ile Pro Ala Val Ala Thr Leu Glu Leu Thr Gly Asp Glu Ala Thr Gly Arg Asn Ile Val Leu Arg Ala Leu Glu Glu Pro Val Arg Gln Ile Ala His Asn Ala Gly Phe Glu Gly Ser Ile Val Ile Asp Arg Leu Lys Asn Ala Glu Leu Gly Ile Gly Phe Asn Ala Ala Thr Gly Glu Trp Val Asn Met Ile Asp Gln Gly Ile Ile Asp Pro Val Lys Val Ser Arg Ser Ala Leu Gln Asm Ala Ala Ser Val Ala Ser Leu Ile Leu Thr Thr Glu Ala Val Val Ala Asn Lys Pro Glu Pro Val Ala Pro Ala 515 520 525 t Pro Ala Met Asp Pro Ser Met Met Gly Gly Met Met <210> 214 <211> 481 5 <212> PRT
<213> Streptococcus pneumoniae <400> 214 Met Ile Lys Ile Glu Thr Val Leu Asp Ile Leu Lys Lys Asp Gly Leu Phe Arg Glu Ile Ile Asp Gln Gly.His Tyr His Tyr Asn Tyr Ser Lys SS Val Ile Phe Asp Ser Ile Ser Tyr Asp Ser Arg Lys Val Thr Glu Asp Thr Leu Phe Phe Ala Lys Gly Ala Ala Phe Lys Lys Glu Tyr Leu Leu Ser Ala Ile Thr Gln Gly Leu Ala Trp Tyr Val Ala Glu Lys Asp Tyr Glu Val Gly Ile Pro Val Ile Ile Val Asn Asp Ile Lys Lys Ala Met Ser Leu Ile Ala Met Glu Phe Tyr Gly Asn Pro Gln Glu Lys Leu Lys Leu Leu Ala Phe Thr Gly Thr Lys Gly Lys Thr Thr Ala Ala Tyr Phe Ala Tyr Asn Ile Leu Ser Gln Gly His Arg Pro Ala Met Leu Ser Thr Met Asn Thr Thr Leu Asp Gly Glu Thr Phe Phe Lys Ser Ala Leu Thr Thr Pro Glu Ser Ile Asp Leu Phe Asp Met Met Asn Gln Ala Val Gln 165 170 . 175 .Asn Asp Arg Thr His Leu Ile Met Glu Val Ser Ser Gln Ala Tyr Leu Val Lys Arg Val Tyr Gly Leu Thr Phe Asp Val Gly Val Phe Leu Asn Ile~Ser Pro Asp His Ile Gly Pro Ile Glu His Pro Sex Phe Glu Asp Tyr Phe Tyr His Lys Arg Leu Leu Met Glu Lys Ser Arg Ala Val Ile Ile Asn Ser Asp Met Asp His Phe Ser Val Leu Lys Glu Gln Val Glu Asp Gln Asp His Asp Phe Tyr Gly Ser.Gln Phe Asp Asn Gln Ile Glu Asn Ser Lys Ala Phe.Ser Phe Se,r Ala Thr Gly Lys Leu Ala Gly Asp Tyr Asp-Ile Gln Leu Ile G1y Asn Phe Asn Gln Glu Asn Ala Val Ala Ala Gly Leu Ala Cys Leu Arg Leu Gly Ala Ser Leu Glu Asp Ile Lys Lys Gly Ile Ala Ala Thr Arg Va1 Pro Gly Arg Met Glu Val Leu Thr $$' Gln Lys Asn Gly Ala Lys Val Phe Ile Asp Tyr Ala His Asn Gly Asp Ser Leu LysLys LeuIleAsn ValValGlu ThrHisGln ThrGlyLys Ile A1a LeuVal LeuGlySer ThrGlyAsn LysGlyGlu SerArgArg Lys Asp PheGly LeuLeu~Leu AsnGlnHis ProGlwTle GlnValPhe 385 390 3'95 400 Leu Thr AlaAsp AspProAsn TyrGluAsp ProMetAla IleAlaAsp Glu Ile SerSer TyrIleAsn HisProVal GluLysIle AlaAspArg Gln Glu AlaIle LysAlaAla MetAlaIle ThrAsnHis GluLeuAsp Ala Val IleIle AlaGlyLys GlyAlaAsp CysTyrGln IleIleGln Gly Lys LysGlu SerTyrPro GlyAspThr AlaValAla GluAsnTyr Leu <210> 215 <211> 659 <212> PRT

<213> Streptococcus pneumoniae <400> 215 Met Ile Ile G1yLysL1e PheAlaGly ArgTyrArg IleValLys Gln Gln Ile Arg GlyGlyMet AlaAspVal TyrLeuAla LysAspLeu Gly 20 . 25 30 Ile Leu Gly GluGluVal AlaValLys ValLeuArg ThrAsnTyr Asp Gln Thr Pro IleAlaVal AlaArgPhe GlnArgGlu AlaArgAla Asp Met Ala Leu AspHisPro HisIleVal ArgIleThr AspIleGly Asp $0 Glu Glu Gly GlnGlnTyr LeuAlaMet GluTyrVal AlaGlyLeu Asp Asp Leu Arg TyrIleLys GluHisTyr ProLeuSer AsnGluGlu Lys Ala Val Ile MetGlyGln IleLeuLeu AlaMetArg LeuAlaHis Arg Thr ArgGlyIle ValHisArg AspLeuLys ProGlnAsn IleLeuLeu Thr ProAspGly ThrAlaLys ValThrAsp PheGlyIle AlaValAla Phe AlaGluThr SerLeuThr GlnThrAsn SerMetLeu GlySerVal His TyrLeuSer ProGluGln AlaArgGly .SerLysAla ThrValGln Ser AspIleTyr A1aMetGly IleIlePhe TyrGluMet LeuThrGly l95 200 205 His IleProTyr AspGlyAsp SerAlaVal ThrIleAla LeuGlnHis Phe GlnLysPro LeuProSer ValIleAla GluAsnPro SerValPro Gln AlaLeuGlu AsnValIle IleLysAla ThrAlaLys LysLeuThr Asn ArgTyrArg SerValSer GluMetTyr ValAspLeu SerSerSer Leu SerTyrAsn ArgArgAsn GluSerLys LeuIlePhe AspGluThr Ser LysAlaAsp ThrLysThr LeuProLys ValSerGln SerThrLeu 5 Thr SerI1ePro LysVa1Gln AlaGlnThr GluHisLys SerIleLys Asn ProSerGln AlaValThr GluGluThr TyrGlnPro GlnAlaPro Lys LysHisArg PheLysMet ArgTyrLeu IleLeuLeu AlaSerLeu Val LeuValAla AlaSerLeu IleTrpIle LeuSerArg ThrProAla 4S 355 . 360 365 Thr IleAlaIle ProAspVal AlaGlyGln ThrValAla GluAlaLys Ala ThrLeuLys LysAla.Asn PheGluIle GlyGluGlu LysThrGlu Ala SerGluLys ValGluGlu .GlyArgIle IleArgThr AspProGly SS

Ala GlyThrGly ArgLysGlu GlyThrLys IleAsnLeu ValValSer 420 425' 430 Ser Gly Lys Gln Ser Phe Gln Ile Ser Asn Tyr Val G1y Arg Lys Ser Ser Asp Val Ile Ala Glu Leu Lys Glu Lys Lys Val Pro Asp Asn Leu 450 . 455 460 I1e Lys Ile Glu Glu Glu Glu Ser Asn Glu Ser Glu Ala Gly Thr Val Leu Lys Gln Ser Leu Pro Glu Gly Thr Thr Tyr Asp Leu Ser Lys Ala Thr Gln Ile Val Leu Thr Val Ala Lys Lys Ala Thr Thr Ile Gln Leu Gly Asn Tyr Ile Gly Arg Asn Ser Thr Glu Val Ile Ser Glu Leu Lys Gln Lys Lys Val Pro Glu Asn Leu Ile Lys Tle Glu Glu Glu Glu Ser Ser Glu Ser Glu Pro Gly Thr Ile Met Lys Gln Ser Pro Gly Ala Gly Thr Thr Tyr Asp Val Ser Lys Pro Thr Gln Ile Val Leu Thr Va1 Ala Lys Lys Val Thr Ser Val Ala Met Pro Ser Tyr Ile Gly Ser Ser Leu 0 580 585 590 ' Glu Phe Thr Lys Asn Asn Leu Ile Gln Ile Val Gly Ile Lys Glu Ala 3$ Asn Ile Glu Val Val Glu Val Thr Thr Ala Pro Ala Gly Ser Ala Glu Gly Met Val Val Glu Gln Ser Pro Arg Ala Gly Glu Lys Val Asp Leu Asn Lys Thr Arg Val Lys Ile Ser Ile Tyr Lys Pro Lys Thr Thr Ser Ala Thr Pro <210> 216 <211> 391 <212> PRT
<213> Streptococcus pneumoniae <400> 216 Met Lys His Phe Asp Thr Ile Val Ile Gly Gly Gly Pro Ala Gly Met Met Ala Thr Ile Ser Ser Asn Phe Tyr Gly Gln Lys Thr Leu Leu Ile Glu Lys Asn Arg Lys Leu Gly Lys Lys Leu Ala Gly Thr Gly Gly Gly Arg Cys Asn Val Thr Asn Asn Gly Ser Leu Asp Asn Leu Leu Ala Gly Ile Pro Gly Asn Gly Arg Phe Leu Tyr Ser Val Phe Ser Gln Phe Asp Asn His Asp Ile Ile Asn Phe Phe Thr Glu Asn G1y Val Lys Leu Lys ISVal GluAspHis GlyArgVal PheProAla Ser_AspLys SerArgThr 100 ' 105 110 Ile IleGlu~Ala LeuGluLys LysIleThr GluLeuGly GlyGlnVal Ala ThrGlnIle GluIleVal SerValLys LysValAsp AspGlnPhe Val LeuLysSer AlaAspGln ThrPheThr CysGluLys LeuIleVal Thr ThrGlyGly LysSerTyr ProSerThr GlySerThr GlyPheGly 30His GluIleAla ArgHisPhe LysHisThr IleThrAsp LeuGluAla 180 . 185 190 Ala GluSerPro LeuLeuThr AspPhePro HisLysAla LeuGlnGly Ile SerLeuAsp AspValThr LeuSerTyr GlyLysHis ValIleThr His AspLeuLeu PheThrHis PheGlyLeu SerGlyPro AlaAlaLeu Arg MetSerSer PheValLys GlyGlyGlu ValLeuSer LeuAspVal 5 Leu ProGlnLeu SerGluLys AspLeuVal ThrPheLeu GluGluAsn Arg GluLysSer LeuLysAsn AlaLeuLys ThrLeuLeu ProGluArg Leu AlaGluPhe PheValGln GlyTyrPro GluLysVal LysGlnLeu 290 . 295 300 Thr GluLysGlu ArgGluGln LeuValGln SerIleLys GluLeuLys Ile ProValThr GlyLysMet SerLeuAla LysSerPhe ValThrLys Gly Gly Val Sex Leu Lys Glu Ile Asn Pro Lys Thr Leu Glu Ser Lys Leu Val Pro Gly Leu His Phe Ala Gly Glu Val Met Asp Ile Asn Ala His Thr Gly Gly Phe Asn Ile Thr Ser Ala Leu Cys Thr Gly Trp Val Ala Gly Ser Leu His Tyr Asp <210> 217 <211> 231 <212> PRT
<213> Streptococcus pneumoniae <400> 217 Met Leu Lys Trp Glu Asp Leu Pro Val Glu Met Lys Ser Ser Glu Val l 5 10 ' 15 Glu Ser Tyr Tyr Gln Leu Val Ser Lys Arg Lys Gly Ser Leu Ile Phe Lys Arg CysLeuAsp TrpValLeu AlaLeuVal LeuThrTrp ValLeu 35 40 ~ 45 Thr Ser ProIlePhe LeuIleLeu SerIleTrp IleLysLeu AspSer Lys Gly ProValIle TyrLysGln GluArgVa1 ThrGlnTyr AsnArg Arg Phe LysIleTrp LysPheArg ThrMetVal ThrAspAla AspLys 4~ Lys Gly SerLeuVal ThrSerAla AsnAspSer ArgIle.ThrLysVal l00' 105 110 Gly Asn PheIleArg ArgValArg LeuAspGlu LeuProGln LeuVal Asn Val LeuLysGly GluMetSer PheValGly ThrArgPro GluVal Pro Arg TyrThrGlu GlnTyrSer ProGluMet MetAlaThr LeuLeu 5~ 145 150 155 160 Leu Gln Ala~GlyIle ThrSerPro AlaSerIle AsnTyrLys AspGlu 5$ Asp Thr Ile Ile Ser Gln Met Thr Glu Lys Gly Leu Ser Val Asp Gln Ala Tyr Val Glu His Val Leu Pro Glu Lys Met Arg Tyr Asn Leu A1a Tyr Leu Arg Glu Phe Ser Phe Phe Gly Asp Ile Lys Ile Met Phe Gln Thr Val Phe Glu Val Leu Lys <210> 21s <211> 140 <212> PRT

<213> Streptococcus pneumoniae <400> 218 Met Thr Pro LeuLeu GluSerArg ArgG1nLeuArg LysCysAla Ser Phe Gln Leu MetSer LeuGluPhe GlyThrAspVal GluThrAla Ala Cys~ Arg Ala TyrThr HisAspArg GluTyrThrAsp ValGlnLeu Phe Pro Ala Leu IleAsp LeuValSer GlyValGlnA1a LysLysGlu Phe Glu Leu Lys GlnIle ThrGlnHis LeuLysAlaGly TrpThrIle Asp Glu Arg Thr LeuVal GluArgAsn LeuLeuArgLeu GlyValPhe Leu Glu Ile Ser PheAsp ThrProGln LeuValAlaVal AsnGluAla Thr Ile Glu Ala LysAsp PheSerAsp GlnLysSerAla ArgPheTle Leu Asn Gly Leu SerGln PheValThr GluGluGln Leu <210> 219 <211> 1179 <212> PRT

<213> Streptococcus pneumoniae <400> 219 Met Tyr Leu Lys GluIle Glu GlnGly Phe Lys Ser Ala Ile Phe Asp Lys Thr Lys Val ValPhe Asp GlyVal Thr Ala Val Gly Gln Val Pro Asn Gly Ser Gly LysSer Asn ThrGlu Ser Leu Arg Ala Ile Trp Leu Gly GluSerSer ValLysSer LeuArgGly GlyLysMetPro AspVal Ile PheA1aGly ThrGluSer ArgLysPro LeuAsnTyrAla SerVa1 Val ValThrLeu AspAsnHis AspGlyPhe IleLysAspAla GlyGln Glu IleArgVal GluArgHis IleTyrArg SerGlyAspSer GluTyr IS Lys IleAspGly LysLysVal ArgLeuArg AspIleHisAsp LeuPhe Leu AspThrGly LeuGlyArg AspSerPhe SexIleIleSer GlnGly Lys ValGluGlu IlePheAsn SerLysPro GluGluArgArg AlaIle Phe G1uGluAla AlaGlyVal LeuLysTyr LysThrArgArg LysGlu Thr GluSerL,ysLeuG1nGln ThrGlnAsp AsnLeuAspArg LeuGlu l80 185 190 Asp IleIleTyr GluLeuAsp AsnGlnIle LysProLeuGlu LysGln A1a GluAsnAla ArgLysPhe,LeuAspLeu GluGlyGlnArg LysAla ' 210 215 220 Ile TyrLeuAsp ValLeuVal AlaGlnIle LysGluAsnLys AlaGlu Leu GluSerThr GluGluGlu LeuAlaGln ValGlnGluLeu LeuMet Ser TyrTyrGln LysArgGlu LysLeuGlu G1aGluAsnGln ThrLeu Lys LysGlnArg GlnAspLeu GlnAlaGlu MetAlaLysAsp GlnGly Ser Leu Met Asp Leu Thr Ser Leu Ile Ser Asp Leu Glu Arg Lys Leu Ala Leu Ser Lys Leu Glu Ser Glu Gln Val Ala Leu Asn Gln G1n Glu Ala Gln Ala Arg.Leu Ala Ala Leu Glu Asp Lys Arg Asn Ser Leu Ser Lys Glu Lys Tyr Asp Lys Glu Ser Ser Leu Ala Leu Leu Glu Gly Asn Leu Val GlnAsnAsn GlnLysLeu AsnArgLeu GluAlaGlu Le.uLeu Ala Phe SerAspAsp ProAspGln MetIleGlu LeuLeuArg GluArg Phe Val AlaLeuLeu GlnGluGlu AlaAspVal SerAsnGln LeuThr Arg I1e GluAsn~GluLeuGluAsn SerArgGln LeuSerGln LysGln 1$ Ala Asp GlnLeuGlu LysLeuLys GluGlnLeu AlaThrAla LysGlu Lys Ala SerGlnGln LysAspGlu LeuGluThr AlaLysVal GlnVal Gln Lys LeuLeuAla AspTyr.GlnAlaIleAla LysGluGln GluGlu Gln Lys ThrSerTyr GlnAlaGln GlnSerGln LeuPheAsp ArgLeu 25'465 470 475 480 Asp Ser LeuLysAsn LysGlnAla ArgAlaGln SerLeuGlu AsnTle Leu Arg AsnHisSer Asn~PheTyr AlaGlyVal LysSerVal LeuGln 500 505 57.0 Glu Lys AspArgLeu GlyGlyIle IleGlyAla ValSerGlu HisLeu Thr Phe AspValTyr TyrGlnThr AlaLeuGlu IleAlaLeu GlyAla Ser Ser GlnHisIle IleValGlu AspGluGlu SerAlaThr LysAla Ile Asp PheLeuLys ArgAsnArg ValGlyArg AlaThrPhe LeuPro S Leu Thr Thr Ile Lys Ala Arg Thr Ile Ser Ser Gln Asn Gln Asp Ala 580 585 . 590 Ile Ala Val Ser Pro Gly Phe Leu Gly Met Ala Asp Glu Leu Val Thr Phe Asp Thr Arg Leu Glu Ala Ile Phe Lys Asn Leu Leu Ala Thr Thr Ala Ile Phe Asp Thr Val Glu His Ala Arg Glu Ala Ala Arg Gln Val Arg Tyr Gln Val Arg Met Val.Thr Leu Asp Gly Thr Glu Leu Arg Thr 645 650 . 655 Gly G1y Ser Tyr Ala Gly G1y Ala Asn Arg Gln Asn Asn Ser Ile Phe Ile Lys Pro Glu Leu Glu Gln Leu Gln Lys Glu Ile Ala Ala Asp Glu Ala Ser Leu Gly Ser Glu Glu Ala Ala Leu Lys Thr Leu Gln Asp Gln Met Ala Ala Leu Thr Glu Arg Leu Glu Ala Ile Lys Ser Gln Gly Glu 1$ Gln Ala Arg Ile Gln Glu Gln Gly Leu Ser Leu A1a Tyr Gln Gln Thr Ser Gln Gln Val Glu Glu Leu Glu Thr Leu Trp Lys Leu Gln Glu Glu Glu Ile Asp Arg Leu Ser Glu Gly Asp Trp Gln Ala Asp Lys Glu Lys Cys Gln Glu Ser Leu Ala Thr Ile Ala Ser Asp Lys Gln Asn Leu Glu Ala Glu Ile Glu Glu Ile Lys Ser Asn Lys Asn Ala Ile Gln Glu Arg Tyr Gln Asn Leu~Gln Glu Glu Val Ala Gln Ala Arg Leu Leu Lys Thr Lys Leu Gln Gly Gln Lys Arg Tyr Glu Val Ala Asp Ile Glu Arg Leu Gly Lys Glu Leu Asp Asn Leu Asn Ile Glu Gln Glu Glu Ile Gln Arg Met Leu Gln Glu Lys Val Asp Asn Leu Glu Lys Val Asp Thr Glu Leu Leu Ser Gln Gln Ala Glu Glu Ser Lys Thr Gln Lys Thr Asn Leu Gln Gln Gly Leu Ile Arg Lys Gln Phe Glu Leu Asp Asp Ile Glu Gly Gln 885 ~ 890 895 Leu Asp Asp Ile Ala Ser His Leu Asp Gln Ala Arg Gln Gln Asn Glu 900 ~ 905 910 Glu Trp Ile Arg Lys Gln Thr Arg Ala Glu Ala Lys Lys Glu Lys Val Ser Glu Arg Leu Arg His Leu Gln Asn Gln Leu Thr Asp Gln Tyr Gln Ile Ser Tyr Thr Glu Ala Leu Glu Lys Ala His Glu Leu Glu Asn Leu Asn Leu Ala Glu Gln Glu Val Gln Asp Leu Glu Lys Ala Ile Arg Ser Leu Gly Pro Val Asn Leu G1u Ala Ile Asp Gln Tyr Glu Glu Val His Asn Arg Leu Asp Phe Leu Asn Ser Gln Arg Asp Asp Ile Leu Ser Ala Lys Asn LeuLeuLeu G1uThrIle ThrGluMet AsnAspGlu ValLys Glu Arg PheLysSer ThrPheGlu AlaIleArg GluSerPhe LysVal Thr Phe LysGlnMet PheGlyGly GlyGlnAla AspLeuIle LeuThr Glu Gly AspLeuLeu ThrAlaGly ValGluIle SerValGln ProPro Gly Lys LysIleGln SerLeuAsn LeuMetSer GlyGlyGlu LysA1a Leu Ser A1aLeuAla LeuLeuPhe SerIleIle ArgValLys ThrIle Pro Phe ValIle~LeuAspGluVal GluAlaAla LeuAspGlu AlaAsn Val Lys ArgPheGly AspTyrLeu AsnArgPhe AspLysAsp SerGln 1125 1130, 1135 Phe Ile ValValThr HisArgLys GlyThrMet AlaAlaAla AspSer Ile Tyr GlyValThr MetGlnGlu SerGlyVal SerLysIle ValSer Val Lys Leu Lys Asp Leu Glu Ser Ile Glu Gly <210> 220 <211> 447 <212> PRT
<213> Streptococcus pneumoniae <400> 220 Met Thr Lys Arg Val Thr Ile Ile Asp Val Lys Asp Tyr Val Gly Gln G1u Val Thr Ile Gly Ala Trp Val Ala Asn Lys Ser Gly Lys Gly Lys Ile Ala Phe Leu Gln Leu Arg Asp Gly Thr Ala Phe Phe Gln Gly Val Ala Phe Lys Pro Asn Phe Val Glu Lys Phe Gly Glu Glu Val Gly Leu Glu Lys Phe Asp Val Ile Lys Arg Leu Ser,Gln Glu Thr Ser Val Tyr Val Thr G1y Ile Val Lys Glu Asp Glu Arg Ser Lys Phe Gly Tyr Glu Leu Asp Ile Thr Asp Ile G1u Val Ile Gly Glu Ser Gln Asp Tyr Pro Ile Thr Pro Lys Glu His Gly Thr Asp Phe Leu Me,t Asp Asn Arg His Leu Trp Leu Arg Ser Arg Lys Gln Val Ala Val Leu Gln Ile Arg Asn Ala Ile Ile Tyr Ala Thr Tyr Glu Phe Phe Asp Lys Asn Gly Phe Met 5 Lys Phe Asp Ser Pro Ile Leu Ser Gly Asn Ala Ala Glu Asp Ser Thr Glu Leu Phe Glu Thr Asp Tyr Phe Gly Thr Pro Ala Tyr Leu Ser Gln Ser Gly Gln Leu Tyr Leu Glu Ala Gly Ala Met Ala Leu Gly Arg Val Phe Asp Phe G1y Pro Val Phe Arg Ala Glu Lys Ser Lys Thr Arg Arg His Leu Thr Glu Phe Trp Met Met Asp Ala Ghu Tyr Ser Tyr Leu Thr His Asp Glu Ser Leu Asp Leu Gln Glu Ala Tyr Val Lys Ala Leu Leu Gln Gly Val Leu Asp Arg Ala Pro Gln Ala Leu Glu Thr Leu Glu Arg Asp Thr Glu Leu Leu Lys Arg Tyr Ile Ala Glu Pro Phe Lys. Arg hle Thr Tyr Asp Gln Ala Ile Asp Leu Leu Gln Glu His Glu Asn Asp Glu Asp Ala Asp Tyr Glu His Leu Glu His Gly Asp Asp Phe Gly Ser Pro His Glu Thr Trp Ile Ser Asn His Phe Gly Val Pro Thr Phe Val Met Asn Tyr Pro Ala Ala.Ile Lys Ala Phe Tyr Met Lys Pro Val Pro Gly Asn Pro Glu Arg Val Leu Cys Ala Asp Leu Leu Ala Pro Glu Gly Tyr Gly Glu Ile Ile Gly Gly Ser Met Arg Glu Glu Asp Tyr Asp Ala Leu Val Ala Lys Met Asp Glu Leu Gly Met Asp Arg Thr Glu Tyr Glu Phe Tyr Leu Asp Leu Arg Lys Tyr Gly Thr Val Pro His Gly Gly Phe Gly Ile Gly Ile Glu Arg Met Val Thr Phe Ala Ala Gly Thr Lys His Ile Arg Glu Ala Ile Pro Phe Pro Arg Met Leu His Arg Ile Lys Pro <210> 221 <211> 308 ~S <212> PRT .
<213> Streptococcus pneumoniae <400> 221 Met Ser Glu Lys Leu Val Glu Ile Lys Asp Leu Glu Ile Ser Phe Gly Glu Gly Ser Lys Lys Phe Va1 Ala Val Lys Asn Ala Asn Phe Phe Ile 35 Asn Lys G1y Glu Thr Phe Ser Leu Val Gly Glu Ser Gly Ser Gly Lys Thr Thr Ile Gly Arg Ala Ile Ile Gly Leu Asn Asp Thr Ser Asn Gly Asp Ile Ile Phe Asp Gly Gln Lys Ile Asn G1y Lys Lys Ser Arg Glu Gln Ala Ala Glu Leu Ile Arg Arg Ile Gln Met Ile Phe Gln Asp Pro Ala Ala Ser Leu Asn Glu Arg Ala Thr Val Asp Tyr Ile Ile Ser Glu $0 Gly Leu Tyr Asn His Arg Leu Phe Lys Asp Glu Glu Glu Arg Lys Glu 115 120 ' 125 Lys Val Gln Asn Ile Ile Arg Glu Val Gly Leu Leu Ala Glu His Leu Thr Arg Tyr Pro His Glu Phe Ser Gly Gly Gln Arg Gln Arg Ile Gly Ile Ala Arg Ala Leu Val Met Gln Pro Asp Phe Val Ile Ala Asp Glu S Pro IleSerAlaLeu AspVal SerValArg AlaGlnVal LeuAsnLeu Leu LysLysPheGln LysGlu LeuGlyLeu ThrTyrLeu PheIleAla His AspLeuSerVal ValArg PheIleSer AspArgIle AlaValIle Tyr LysGlyValIle ValGlu ValAlaGlu ThrGluGlu LeuPheAsn Asn ProIleHisPro TyrThr GlnAla.LeuLeuSerAla ValProIle Pro AspProIleLeu GluArg LysLysVal LeuLysVal TyrAspPro Ser GlnHisAspTyr GluThr AspLysPro SerMetVal GluIleArg Pro GlyHisTyrVal TrpAla AsnGlnThr GluLeuAla ArgTyrGln Lys GlyLeuAsn <210>

<211>

3S <212>
PRT

<213> pneumoniae Streptococcus <400>

Met LysIleSerTrp AsnGly PheSerLys LysSerTyr GlnGluArg 1 5 , 10 15 Leu GluLeuLeuLys AlaGln AlaLeuLeu SerProGlu ArgGlnAla 4S Ser LeuGluLysAsp GluGln MetSerVal ThrValAla Asp.GlnLeu Ser GluAsnValVal.GlyThr PheSerLeu ProTyrSer LeuValPro 50 55 60 ' SO

Glu ValLeuValAsn GlyGln GluTyrThr ValProTyr ValThrGlu Glu ProSerValVal AlaAla AlaSerTyr AlaSerLys IleIleLys SS 85 90 ~ 95 Arg Ala Gly Gly Phe Thr Ala Gln Val His Gln Arg Gln Met Ile Gly Gln Val AlaLeu TyrGlnIle AlaAsnPro LysLeuAlaGln GluLys S

Ile Ala SerLys LysAlaGlu LeuLeuGlu LeuA1aAsnGln AlaTyr 130 l35 140 Pro Ser IleVal LysArgGly GlyGlyAla ArgAspLeuHis ValGlu Gln Ile LysGly GluProAsp PheLeuVal ValTyrIleHis ValAsp Thr Gln GluAla MetGlyAla AsnMetLeu AsnThrMetLeu GluAla Leu Lys ProVal LeuGluGlu LeuSerGln GlyGlnSer~Leu MetG1y ~

Ile Leu SerAsn TyrAlaThr AspSerLeu ValThrAlaSer CysArg Ile Ala PheArg TyrLeuSer ArgGlnLys AspGlnGlyArg GluIle 225 230 235 ~ 240 Ala Glu LysIle AlaLeuA1a SerGlnPhe AlaGlnAlaAsp ProTyr Arg Ala AlaThr HisAsnLys GlyIlePhe AsnGlyIleAsp AlaIle Leu Ile AlaThr GlyAsnAsp TrpArgAla TleGluAlaGly AlaHis Ala Phe AlaSer ArgAspGly ArgTyrGln GlyLeuSerCys TrpThr Leu Asp LeuGlu ArgGluGlu LeuValGly GluMetThrLeu ProMet Pro Val AlaThr LysGlyGly SerIleGly LeuAsnProArg ValAla .325 330 335 Leu Ser His Asp Leu Leu Gly Asn Pro Ser A1a Arg Glu Leu Ala Gln Ile Ile Va1 Ser I1e Gly Leu Ala Gln Asn Phe Ala Ala Leu Lys Ala Leu Val Ser Thr Gly Ile Gln Gln Gly His Met Lys Leu Gln Ala Lys Ser Leu Ala Leu Leu Ala Gly Ala Ser Glu Ser Glu_ Val Ala Pro Leu Val Glu Arg Leu Ile Ser Asp Lys Thr Phe Asn Leu Glu Thr Ala Gln Arg Tyr Leu Glu Asn Leu Arg Sex <210> 223 <211> 262 <212> PRT
<213> Streptococcus pneumoniae <400> 223 Met Pro Ile Thr Ser Leu Glu Ile Lys Asp Lys Thr Phe Gly Thr Arg Phe Arg Gly Phe Asp Pro Glu Glu Val Asp Glu Phe Leu Asp Ile Val Val Arg Asp Tyr Glu Asp Leu Val Arg A1a Asn His Asp Lys Asn Leu Arg Ile LysSerLeu GluGluArg LeuSerTyr PheAspGlu IleLys 5 Asp Ser LeuSerGln SerValLeu IleAlaGln AspThrAla GluArg 65 70 75 gp Val Lys GlnAlaAla HisGluArg SerAsnAsn IleIleHis GlnA1a Glu Gln AspAlaGln ArgLeuLeu GluGluAla LysTyrLys AlaAsn 100 105 , 110 Glu Ile LeuArgGln AlaThrAsp AsnAlaLys LysValAla ValGlu Thr Glu GluLeuLys AsnLysSer ArgValPhe HisGlnArg LeuLys Ser Thr IleGluSer GlnLeuAla IleValGlu SerSerAsp TrpGlu 145 150 155 ' 160 Asp Ile LeuArgPro ThrAlaThr TyrLeuGln ThrSerAsp GluA1a Phe Lys GluValVal SerGluVal LeuGlyGlu ProIlePro AlaPro Ile Glu GluGluPro IleAspMet ThrArgGln PheSerGln AlaGlu Met Ala GluLeuGln AlaArgIl.eGluValAla AspLysGlu LeuSer SS Glu Phe GluAlaGln IleLysGln GluValGlu AlaProThr ProVal Val Ser Pro G1n Val Glu Glu Glu Pro Leu Leu Ile Gln Leu Ala Gln Cys Met Lys Asn G1n Lys <210> 224 <211> 575 I0 <212> PRT
<213> Streptococcus pneumoniae <400> 224 Met Ser Asn Gly Gln Leu Ile Tyr Leu Met Val Ala Ile Ala Val Ile Leu Val Leu Ala Tyr Val Val Ala Ile Phe Leu Arg Lys Arg Asn Glu 0 G1y Arg Leu Glu Ala Leu Glu Glu Arg Lys Glu Glu Leu Tyr Asn Leu Pro ValAsnAsp G1uValGlu AlaValLys AsnMetHis LeuIleGly Gln SerGlnVal AlaPheArg GluTrpAsn GlnLysTrp ValAspLeu Ser LeuAsnSer PheAlaAsp IleGluAsn AsnLeuPhe GluAlaGlu Gly TyrAsnHis SerPheArg PheLeuLys AlaSerHis GlnIleAsp $ Gln IleGluSer GlnIleThr LeuIleGlu GluAspIle AlaAlaIle Arg AsnAlaLeu AlaAspLeu GluLysGln GluSerLys AsnSerGly Arg ValLeuHis AlaLeuAsp LeuPheG1u GluLeuGln HisArgVal Ala GluAsnSer GluGlnTyr GlyGlnAla LeuAspGlu IleGluLys 45 16 5 170 l75 Gln LeuGluAsn IleGlnSer GluPheSer GlnPheVal ThrLeuAsn 50 Ser SerGlyAsp ProValGlu AlaAlaVal IleLeuAsp AsnThrGlu Asn HisIleLeu AlaLeuSer HisIleVal AspArgVal ProAlaLeu Va'1 ThrThrLeu.SerThrGlu LeuProAsp GlnLeuGln AspLeuGlu Ala Gly Tyr Arg Lys Leu Ile Asp Ala Asn Tyr His Phe Val Glu Thr Asp Ile GluAlaArg PheHisLeu ZeuTyrGlu AlaPheLys LysAsn 260. 265 270 Gln Glu AsnIleArg GlnLeuGlu LeuAspAsn AlaGluTyr GluAsn Gly Gln AlaGlnGlu GluIleAsn AlaLeuTyr AspIlePhe ThrArg Glu Ile AlaAlaGln LysValVal GluAsnLeu LeuAlaThr LeuPro Thr Tyr LeuGlnHis MetLysGlu Asn.AsnThr LeuLeuG1y GluAsp Ile Ala ArgLeuAsn LysThrTyr LeuLeuPro GluThrAla AlaSer 340 ~ 345 350 His Val ArgArgIle GlnThrGlu LeuG1uSer PheGluA1a AlaIle Val Glu ValThrSer AsnGlnGlu GluProThr GlnAlaTyr SerVal Leu Glu GluAsnLeu GluAspLeu GlnThrGln LeuLysAsp Ile.Glu Asp Glu GlnIleSer ValSerGlu ArgLeuThr.GlnIleGlu LysAsp Asp Ile Asn Ala Arg Gln Lys Ala Asn Val Tyr Val Asn Arg Leu His Thr Ile LysArgTyr MetGlu LysArgAsn LeuProGly IleProGln Thr Rhe LeuLysLeu PhePhe Thr~AlaSer AsnAsnThr GluAspLeu Met Val GluLeuGlu GlnLys ~MetIleAsn IleGluSer ValThrArg Val Leu GluTleAla ThrAsn AspMetGlu AlaLeuGlu ThrGluThr SO Tyr Asn IleValGln TyrAla ThrLeuThr GluGlnLeu LeuGlnTyr ~

Ser Asn ArgTyrArg SerPhe AspG1uArg IleGlnGlu AlaPheAsn Glu Ala LeuAspTle PheGlu LysGluPhe AspTyrHis AlaSerPhe Asp Lys Ile Ser Gln Ala Leu G1u Va1 Ala Glu Pro Gly Val Thr Asn $ Arg Phe Val Thr Ser Tyr Glu Lys Thr Arg Glu Thr Ile Arg Phe <210> 225 <211> 800 <212> PRT
<213> Streptococcus pneumoniae <400> 225 1$ Met Leu Ile Ser Tyr Lys Trp Leu Lys Glu Leu Val Asp Ile Asp Val Pro Ser Gln Glu Leu Ala Glu Lys Met Ser Thr Thr Gly Ile Glu Val Glu GlyVal GluSerPro AlaAlaGly LeuSerLys IleValVal Gly Glu ValLeu SerCysGlu AspValPro GluThrHis LeuHisVal Cys Gln ValAsn ValGlyGlu GluGluArg GlnIleVal CysGlyAla Pro Asn ValArg A1aGlyIle LysValMet ValAlaLeu ProGlyAla Arg Ile AlaAsp AsnTyrLys IleLysLys GlyLysIle ArgGlyLeu Glu Ser LeuGly MetIleCys SerLeuGly GluLeuGly IleSerAsp Ser Val ValPro LysGluPhe AlaAspGly IleGlnIle LeuPro,Glu Asp Ala ValPro GlyGluGlu ValPheSer TyrLeuAsp LeuAspAsp Glu Ile IleGlu LeuSerIle ThrProAsn ArgAlaAsp AlaLeuSer Met Cys GlyVal AlaHisGlu ValAlaAla IleTyrAsp LysAlaVal Asn ~

Phe LysGlu PheThrLeu ThrGluThr AsnGluAla AlaAlaAsp Ala Leu SerVa1 SerIleGlu ThrAspLys AlaProTyr TyrAlaAla Arg Ile LeuAsp AsnValThr IleAlaPro SerProGln TrpLeuGln Asn Leu Leu Met Asn Glu Gly Ile Arg Pro Ile Asn Asn Val Val Asp Val Thr Asn Tyr Ile Leu Leu Tyr Phe Gly Gln Pro Met His Ala Phe Asp Leu Asp Asn Phe Glu Gly Thr Asp Ile Arg Val Arg Glu Ala Arg A1a Gly Glu Lys Leu Val Thr Leu Asp Gly Glu Glu Arg Asp Leu Asp Val Asn Asp Leu Val Ile Thr Va1 Ala Asp Lys Pro Val Ala Leu Ala G1y Val Met Gly Gly Gln Ala Thr Glu Ile Ser Glu Lys Ser Ser Arg Val Val Leu Glu Ala Ala Val Phe Asn Gly Lys Ser Ile Arg Lys Thr Ser Gly Arg Leu Asn Leu Arg Ser Glu Ser Ser Ser Arg Phe Glu Lys Gly Ile Asn Val Ala Thr Val Asn G1u Ala Leu Asp Ala Ala Ala Ser Leu Ile Ala Glu Leu Ala Gly Ala Thr Val Arg Lys Gly Ile Val Ser Ala Gly Glu Leu Asp Thr Ser Asp Val Glu Val Ser Ser Thr Leu Ala Asp Val Asn Arg Val Leu Gly Thr Glu Leu Ser Tyr Ala Asp Val Glu Asp 420 ' 425 430 Val Phe Arg Arg Leu Gly Phe Gly Leu Ser Gly Asn Ala Asp Ser Phe Thr Val Arg Val Pro Arg Arg Arg Trp Asp Ile Thr Ile Glu Ala Asp 5 Leu Phe Glu Glu Ile Ala Arg Ile Tyr Gly Tyr Asp Arg Leu Pro Thr Ser Leu Pro Lys Asp Asp Gly Thr Ala Gly Glu Leu Thr Ala Thr Gln Lys Leu Arg Arg Gln Val Arg Thr Ile Ala Glu Gly Ala Gly Leu Thr Glu Ile 21e Thr Tyr Thr Leu Thr Thr Pro Glu Lys Ala Val Glu Phe Thr Ala Gln Pro Ser Asn Leu Thr Glu Leu Met Trp Pro Met Thr Val 530 535 ' 540 Asp Arg SerValLeu ArgGlnAsn MetIleSer GlyIleLeu AspThr ~

Val Ala TyrAsnVal AlaArgLys AsnLysAsn LeuAlaLeu TyrGlu Ile Gly LysValPhe ~GluGlnThr GlyAsnPro LysGluGlu LeuPro Asn Glu IleAsnSer PheAlaPhe AlaLeuThr G1yLeuVa1 AlaGlu IS Lys Asp PheGlnThr AlaAlaVal ProValAsp PhePheTyr AlaLys Gly Ile LeuGluAla LeuPheThr ArgLeuGly LeuGlnVal ThrTyr Thr Ala ThrSerGlu IleA1aSer LeuHisPro GlyArgThr AlaVal Ile Ser LeuGlyAsp GlnValLeu GlyPheLeu GlyGlnVal HisPro Val Thr AlaLysAla TyrAspIle ProGluThr TyrValAla GluLeu Asn Leu SerAlaIle GluAlaAla LeuGlnPro AlaThrPro PheVal Glu Ile ThrLysPhe ProAlaVal SerArgAsp ValAlaLeu LeuLeu Lys Ala GluValThr HisGlnGlu ValValAsp AlaIleGln AlaAla Gly Val LysArgLeu ThrAspIle LysLeuPhe AspValPhe SerGly Glu Lys LeuGlyLeu GlyMetLys SerMetAla TyrSerLeu ThrPhe Gln Asn ProGluAsp SerLeuThr AspGluGlu ValAlaArg TyrMet Glu Lys IleGlnAla SerLeuGlu GluLysVal AsnAlaGlu ValArg <210> 226 <211> 180 <212> PRT

<213> pneumoniae Streptococcus <400>

Met Leu G1uAsn AspIleLysLys ~ValLeu ValSerHisAsp GluIle $ 1 5 10 Z5 Thr Glu AlaAla LysLysLeuGly AlaGln LeuThrLysAsp TyrAla Gly Lys AsnPro IleLeuValGly IleLeu LysGlySerIle ProPhe Met Ala GluLeu ValLysHisIle AspThr HisIleGluMet AspPhe Met Met ValSer SerTyrHisGly GlyThr AlaSerSerGly ValIle 65 70 75 g0 Asn Ile LysGln AspValThrG1n AspIle LysGlyArgHis ValLeu Phe Val GluAsp IleIleAspThr GlyGln ThrLeuLysAsn LeuArg Asp Met PheLys AlaArgGluAla AlaSer ValLysIleAla ThrLeu 115 12.0 125 Leu Asp LysPro GluGlyArgVal ValGlu TleGluAlaAsp TyrThr Cys Phe ThrIle ProAsnGluPhe ValVal GlyTyrGlyLeu AspTyr .

Lys Glu AsnTyr ArgAsnLeuPro TyrIle GlyValLeuLys GluGlu Val Tyr Ser Asn .

Claims (102)

What is claimed is:

1. An isolated nucleic acid molecule encoding a polypeptide which is (1) essential for the viability of a bacterial cell and (2) has at least any one of the functions of a pantothenate kinase, a Holliday Junction branch migration protein, a single stranded DNA binding protein, a phosphoglucosamine mutase, an acetyltransferase, an uridylyltransferase, a malonyl CoenzymeA:ACP
transcylase, a 3-oxoacyl-ACP synthase II, a 3-oxoacyl-ACP reductase, a phosphomethylpyrimidine (HMP-P) kinase, a GTP binding protein, a ATP
binding protein, or a 4-aminoimidazole carboxylase.

2. The isolated nucleic acid molecule of claim 1, wherein the nucleic acid molecule is shown in SEQ ID NO:97 or Figure 115 and wherein the polypeptide is a pantothenate kinase.

3. The isolated nucleic acid molecule of claim l, wherein the nucleic acid molecule is shown in SEQ ID NO:35, Figure 60, SEQ ID NO:19, or Figure 44,and wherein the polypeptide is a Holliday Junction branch migration protein.

4. The isolated nucleic acid molecule of claim 1, wherein the nucleic acid molecule is shown in SEQ ID NO:8 or Figure 33 and wherein the polypeptide is a single stranded DNA binding protein.

5. The isolated nucleic acid molecule of claim 1, wherein the nucleic acid molecule is shown in SEQ ID NO:3 or Figure 28 and wherein the polypeptide is a phosphoglucosamine mutase.

6. The isolated nucleic acid molecule of claim 1, wherein the nucleic acid molecule is shown in SEQ ID NO:82 or Figure 103 arid wherein the polypeptide is a acetyltransferase.

7. The isolated nucleic acid molecule of claim 1, wherein the nucleic acid molecule is shown in SEQ ID NO:82 or Figure 103 and wherein the polypeptide is a uridylyltransferase.

8. The isolated nucleic acid molecule of claim 1, wherein the nucleic acid molecule is shown in SEQ ID NO:30 or Figure 55 and wherein the polypeptide is a malonyl CoenzymeA:ACP transcylase.

9. The isolated nucleic acid molecule of claim 1, wherein the nucleic acid molecule is shown in SEQ ID NO:86 or Figure 107 and wherein the polypeptide is a 3-oxoacyl-ACP synthase II.

10. The isolated nucleic acid molecule of claim 1, wherein the nucleic acid molecule is shown in SEQ ID NO:31 or Figure 56 and wherein the polypeptide is a 3-oxoacyl-ACP reductase.

11. The isolated nucleic acid molecule of claim 1, wherein the nucleic acid molecule is shown in SEQ ID NO:36 or Figure 61 and wherein the polypeptide is a phosphomethylpyrimidine (HMP-P) kinase.

12. The isolated nucleic acid molecule of claim 1, wherein the nucleic acid molecule is shown in SEQ ID NO:37, Figure 62, SEQ ID NO:48, or Figure 73, and wherein the polypeptide is a GTP binding protein.

13. The isolated nucleic acid molecule of claim 1, wherein the nucleic acid molecule is shown in SEQ ID NO:42 or Figure 67 and wherein the polypeptide is a ATP
binding protein.

14. The isolated nucleic acid molecule of claim 1, wherein the nucleic acid molecule is shown in SEQ ID NO:84 or Figure 105 and wherein the polypeptide is a 4-aminoimidazole carboxylase.

15. The isolated nucleic acid molecule of claim 1, wherein the nucleic acid molecule is shown in SEQ ID NO:48 or Figure 73 and wherein the polypeptide is a GTP
binding protein.

16. An isolated nucleic acid molecule encoding a polypeptide which is essential for the viability of a bacterial cell, the nucleic acid molecule comprising a sequence shown in any one of SEQ ID NOS:1-113.

17. An isolated nucleic acid molecule encoding a polypeptide which is essential for the viability of a bacterial cell, the nucleic acid molecule comprising a sequence shown in any one of Figures 26-130.

18. An isolated nucleic acid molecule encoding any one of a polypeptide designated CFE 1-117 having the amino acid sequence shown in SEQ ID NO:114-226.

19. An isolated nucleic acid molecule comprising a nucleotide sequence which is complementary to the nucleotide sequence of claim 1, 16, 17 or 18.

20. The isolated nucleic acid molecule of claim 1, 16, 17 or 18 which is DNA
or RNA.

21. The isolated nucleic acid molecule of claim 20, which is labeled with a detectable marker.

22. The isolated nucleic acid molecule of claim 21, wherein the detectable marker is selected from the group consisting of a radioisotope, a fluorescent compound, a bioluminescent compound, a chemiluminescent compound, a metal chelator and an enzyme.

23. A vector comprising the nucleotide sequence of claim 1, 16, 17, or 18.

24. A host-vector system comprising the vector of claim 23, in a suitable host cell.

25. The host-vector system of claim 24, wherein the suitable host cell is selected from a group consisting of a yeast cell, a plant cell, and an animal cell.

26. The host-vector system of claim 24, wherein the suitable host cell is selected from a group consisting of an Escherichia cell, a Bacillus cell, a Pseudomonas cell, a Streptococcus cell, and a Streptomyces cell.

27. An isolated polypeptide which is essential for the viability of a bacterial cell comprising the amino acid sequence as shown in any one of SEQ. ID NOS: 114-226.

28. An isolated polypeptide which is essential for the viability of a bacterial cell encoded by the isolated nucleic acid molecule of claim 1, 16, 17, or 18.

29. The isolated polypeptide of claim 27 or 28 which is a fusion polypeptide.

30. A method for producing a polypeptide having the amino acid sequence of any one of SEQ ID NOS: 114-226 or a polypeptide encoded by the polynucleotide sequence as shown in any one of Figures 26-130, comprising:
a) culturing the host-vector system of claim 24 under suitable conditions so as to produce the polypeptide; and b) recovering the polypeptide so produced.

31. A polypeptide produced by the method of claim 30.

32. A ligand which binds the polypeptide of claim 27 or 28.

33. The ligand of claim 32 which is an antibody or an immunologically active fragment thereof.

34. The ligand of claim 33, wherein the antibody is a monoclonal antibody.

35. The ligand of claim 32 which is a diazalactone.

36. The ligand of claim 35, wherein the diazalactone comprises the structure:

37. The ligand of claim 32 which is a N-protected amino acid.

38. The ligand of claim 37, wherein the N-protected amino acid comprises the structure:

39. The ligand of claim 32 which is an azabicyclodiene.

40. The ligand of claim 39, wherein the azabicyclodiene comprises the structure:

41. The ligand of claim 32 which is an alkaloid.

42. The ligand of claim 41, wherein the alkaloid comprises the structure:

43. The ligand of claim 41, wherein the alkaloid comprises the structure:

44. The ligand of claim 41, wherein the alkaloid comprises the structure:

45. The ligand of claim 41, wherein the alkaloid comprises the structure:

46. The ligand of claim 41, wherein the alkaloid comprises the structure:

47. A method for detecting the presence of the polypeptide of claim 27 or 28 in a sample, comprising contacting the sample with a ligand which binds the polypeptide and detecting the binding of the polypeptide with the ligand in the sample.

48. The method of claim 47, wherein the detecting comprises:
a) contacting the sample with the ligand; and b) determining whether a polypeptide-ligand complex is so formed.

49. The method of claim 47, wherein the sample is a cell, a tissue, or a biological fluid.

50. The method of claim 47, wherein the sample is blood, serum, a swab from nose, a swab from ear, or a swab from throat.

51. The method of claim 47, wherein the ligand is a diazalactone.

52. The method of claim 51, wherein the diazalactone comprises the structure:

53. The method of claim 47, wherein the ligand is a N-protected amino acid.

54. The method of claim 53, wherein the N-protected amino acid comprises the structure:

55. The method of claim 47, wherein the ligand is an azabicyclodiene.

56. The method of claim 55, wherein the azabicyclodiene comprises the structure:

57. The ligand of claim 47 which is an alkaloid.

58. The ligand of claim 57, wherein the alkaloid comprises the structure:

59. The ligand of claim 57, wherein the alkaloid comprises the structure:

60. The ligand of claim 57, wherein the alkaloid comprises the structure:

61. The ligand of claim 57, wherein the alkaloid comprises the structure:

62. The ligand of claim 57, wherein the alkaloid comprises the structure:

63. A method for detecting the presence of a target nucleic acid molecule as shown in any one of SEQ ID NOS:1-113 in a sample, comprising contacting the sample with the complementary nucleic acid molecule of claim 19 and detecting the binding of the target nucleic acid molecule with the complementary nucleic acid molecule in the sample.

64. The method of claim 63, wherein the detecting comprises:
a) contacting the sample with the complementary nucleic acid molecule; and b) determining whether a complex comprising the target nucleic acid molecule and the complementary nucleic acid molecule is so formed.

65. The method of claim 63, wherein the sample is a cell, a tissue, or a biological fluid.

66. The method of claim 63, wherein the sample is blood, serum, a swab from nose, a swab from ear, or a swab from throat.

67. A pharmaceutical composition comprising the nucleic acid molecule of claim 1, 16, 17, or 18.

68. A pharmaceutical composition comprising the polypeptide of claim 27 or 28.

69. A pharmaceutical composition comprising the ligand of claim 32.

70. A method for determining whether a genomic nucleotide sequence of interest is essential for viability of a bacterial cell, comprising a. integrating an exogenous nucleotide sequence into the genomic nucleotide sequence of interest, wherein the exogenous nucleotide sequence comprises a portion of an open reading frame of the genomic nucleotide sequence of interest, and b. determining whether the cell having the genomic nucleotide sequence of interest so integrated is viable.

71. The method of claim 70, wherein the portion of the open reading frame comprises about 200 to 500 base pairs in length.

72. The method of claim 70, wherein the exogenous nucleotide sequence further comprises a nucleotide sequence conferring a selectable phenotype to the cell having the genome so integrated.

73. The method of claim 70, wherein determining comprises selecting the cell having the genome so integrated in the presence of a selection agent.

74. The method of claim 73, wherein the selection agent is chloramphenicol.

75. A nucleotide sequence of interest which is essential for viability of a bacterial cell isolated by the method of claim 70.

76. A bacterial cell comprising an exogenous nucleotide sequence integrated into the genomic nucleotide sequence of interest, generated by the method of claim 70.

77. A method for determining whether a genomic nucleotide sequence of interest resides within an operon, comprising a) integrating an exogenous nucleotide sequence into the genomic nucleotide sequence of interest; and b) determining whether the cell having the genomic nucleotide sequence of interest so integrated is viable, and wherein the exogenous nucleotide sequence lacks an expression regulatory sequence.

78. The method of claim 77, wherein the exogenous nucleotide sequence further comprises a nucleotide sequence conferring a selectable phenotype to the cell having the genome so integrated.

79. The method of claim 77, wherein determining comprises selecting the cell having the genome so integrated in the presence of a selection agent.

80. The method of claim 79, wherein the selection agent is chloramphenicol.

81. A method for inhibiting a function of a CEG polypeptide which is essential for viability of a bacterial cell, the method comprising contacting the CEG
polypeptide with the ligand of claim 32 under suitable conditions thereby inhibiting the function of the CEG polypeptide.

82. The method of claim 81, wherein the function of the CEG polypeptide is selected from a group consisting of a pantothenate kinase, a Holliday Junction branch migration protein, a single stranded DNA binding protein, a phosphaglucosamine mutase, an acetyltransferase, an uridylyltransferase, a malonyl CoenzymeA:ACP
transcylase, a 3-oxoacyl-ACP synthase II, a 3-oxoacyl-ACP reductase, a phosphomethylpyrimidine (HMP-P) kinase, a GTP binding protein, a ATP
binding protein, or a 4-aminoimidazole carboxylase.

83. The method of claim 81, wherein the CEG polypeptide is selected from a group consisting of CFE1-113.

84. The method of claim 81, wherein the CEG polypeptide is 2CFE 34 shown in Figure 55.

85. The method of claim 81, wherein the CEG polypeptide is 2CFE 43 shown in Figure 64.

86. The method of claim 81, wherein the CEG polypeptide is 2CFE 34 shown in Figure 55 and the ligand is:

87. The method of claim 81, wherein the CEG polypeptide is 2CFE 43 shown in Figure 64 and the ligand is:

88. The method of claim 81, wherein the CEG polypeptide is 2CFE 43 shown in Figure 64 and the ligand is:

89. A method for identifying a ligand in a sample which specifically binds a CEG
polypeptide, the method comprising:
a) contacting the CEG polypeptide with the sample under suitable conditions so that a complex having the CEG polypeptide and the ligand is formed;
b) recovering the complex so formed; and c) separating the CEG polypeptide from the ligand in the complex and identifying the ligand so separated.

90. The method of claim 89, wherein the sample is a tissue or biological fluid.

91. The method of claim 89, wherein the ligand is an azabicyclodiene.

92. The method of claim 91, wherein the azabicyclodiene comprises the structure:

93. The method of claim 89, wherein the ligand is a diazalactone.

94. The method of claim 93, wherein the diazalactone comprises the structure:

95. The method of claim 89, wherein the ligand is a N-protected amino acid.

96. The method of claim 95, wherein the N-protected amino acid comprises the structure:

97. The method of claim 89, wherein the ligand is an alkoloid.

98. The ligand of claim 97, wherein the alkaloid comprises the structure:

99. The ligand of claim 97, wherein the alkaloid comprises the structure:

100. The ligand of claim 97, wherein the alkaloid comprises the structure:

101. The ligand of claim 97, wherein the alkaloid comprises the structure:

102. The ligand of claim 97, wherein the alkaloid comprises the structure:
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