NOVEL STREPTOCOCCAL ERS

Abstract: The invention provides gluS polypeptides and DNA (RNA) encoding gluS polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing gluS polypeptides to screen for antibacterial compounds.

Description: NOVEL STREPTOCOCCAL ERS FIELD OF THE INVENTION This invention relates to newly identified polynucleotides and polypeptides, and their production and uses, as well as their variants, agonists and antagonists, and their uses. In particular, in these and in other regards, the invention relates to novel polynucleotides and polypeptides of the glutamyl tRNA synthetase family, hereinafter referred to as "gluS". BACKGROUND OF THE INVENTION The Streptococci make up a medically important genera of microbes known to cause several types of disease in humans, including, for example, otitis media, conjunctivitis, pneumonia, bacteremia, meningitis, sinusitis, pleural empyema and endocarditis, and most particularly meningitis, such as for example infection of cerebrospinal fluid. Since its isolation more than 100 years ago, Streptococcus pneumoniae has been one of the more intensively studied microbes. For example, much of our early understanding that DNA is, in fact, the genetic material was predicated on the work of Griffith and of Avery, Macleod and McCarty using this microbe. Despite the vast amount of research with S. pneumoniae, many questions concerning the virulence of this microbe remain. It is particularly preferred to employ Streptococcal genes and gene products as targets for the development of antibiotics. The frequency of Streptococcus pneumoniae infections has risen dramatically in the past 20 years. This has been attributed to the emergence of multiply antibiotic resistant strains and an increasing population of people with weakened immune systems. It is no longer uncommon to isolate Streptococcus pneumoniae strains which are resistant to some or all of the standard antibiotics. This has created a demand for both new anti-microbial agents and diagnostic tests for this organism. The t-RNA synthetases have a primary role in protein synthesis according to the following scheme: Enzyme +ATP + AA <t=> Enzyme.AA-AMP + PPi Enzyme.AA-AMP + t-RNA Enzyme + AMP + AA-t-RNA in which AA is an amino acid. Inhibition of this process leads to a reduction in the levels of charged t-RNA and this triggers a cascade of responses known as the stringent response, the result of which is the induction of a state of dormancy in the organism. As such selective inhibitors of bacterial t- RNA synthetase have potential as antibacterial agents. One example of such is mupirocin which is a selective inhibitor of isoleucyl t-RNA synthetase. Other t-RNA synthetases are now being examined as possible anti-bactenal targets, this process being greativ assisted bv the isolation of the synthetase Clearly, there is a need for factors, such as the novel compounds of the invention, that have a present benefit of being useful to screen compounds for antibiotic activity Such factors are also useful to determine their role in pathogenesis of infection, dysfunction and disease There is also a need for identification and characterization of such factors and their antagonists and agonists which can play a role in preventing, ameliorating or correcting infections, dysfunctions or diseases The polypeptides of the invention have amino acid sequence homology to a known Bacillus subtihs glutamyl tRNA synthetase protein SUMMARY OF THE INVENTION It is an object of the invention to provide polypeptides that been identified as novel gluS polvpeptides bv homology between the amino acid sequence set out in Table 1 [SEQ ID NO 2] and a known amino acid sequence or sequences of other proteins such as Bacillus subtihs giutamvl tRNA s\ nthetase protein It is a further object of the invention to provide polynucleotides that encode gluS polypeptides, particularly polynucleotides that encode the poiypeptide herein designated gluS In a particularly preferred embodiment of the invention the polynucleotide comprises a region encoding gluS polypeptides compπsing the sequence set out in Table 1 [SEQ ID NO 1], or a vaπant thereof In another particularly preferred embodiment of the invention there is a novel gluS protein from Streptococcus pneumoniae compπsing the amino acid sequence of Table 1 [SEQ ID NO 2] or a vaπant thereof In accordance with another aspect of the invention there is provided an isolated nucleic acid molecule encoding a mature poiypeptide expressible by the Streptococcus pneumoniae 0100993 strain contained in the deposited strain A further aspect of the invention there are provided isolated nucleic acid molecules encoding gluS, particularly Streptococcus pneumoniae gluS, including mRNAs cDNAs, geπomic DNAs Further embodiments of the invention include biologicalK. diagnostically, prophylacticalK , chnicallv or therapeuticalK useful . aπants thereof, and compositions compπsing the same In accordance with another aspect of the invention, there is prov ided the use of a polynucleotide of the invention for therapeutic or prophylactic purposes, in particular genetic immunization Among the particularly prererred embodiments of the invention are naturally occurπng alle c vaπants of gluS and polypeptides encoded thereby Another aspect of the invention there are provided novel polypeptides of Streptococcus pneumoniae referred to herein as gluS as well as biologicallv. diagnostically, prophylactically. clinically or therapeutically useful vaπants thereof, and compositions compπsing the same Among the particularly preferred embodiments of the invention are vaπants of gluS poiypeptide encoded by naturally occurπng alleles of the gluS gene In a preferred embodiment of the invention there are provided methods for producing the aforementioned gluS polypeptides In accordance with yet another aspect of the invention, there are provided inhibitors to such polypeptides, useful as antibacterial agents, including, for example, antibodies In accordance with certain preferred embodiments of the invention, there are provided products, compositions and methods for assessing gluS expression, treating disease, for example, otitis media, conjunctivitis, pneumonia, bacteremia. meningitis, sinusitis, pleural empyema and endocarditis, and most particularly meningitis, such as for example infection of cerebrospinal fluid, assaying genetic vaπation, and administeπng a gluS poiypeptide or polynucleotide to an organism to raise an immunological response against a bacteπa, especialK a Streptococcus pneumoniae bacteπa. In accordance with certain preferred embodiments of this and other aspects of the invention there are provided polynucleotides that hvbπdize to gluS polynucleotide sequences, particularly under stπngent conditions In certain preferred embodiments of the invention there are provided antibodies against gluS polypeptides In other embodiments of the invention there are provided methods for identifying compounds which bind to or otherwise interact with and inhibit or activate an activity of a poiypeptide or polynucleotide of the invention compπsing contacting a poiypeptide or polynucleotide of the invention with a compound to be screened under conditions to permit binding to or other interaction between the compound and the poiypeptide or polynucleotide to assess the binding to or other interaction with the compound, such binding or interaction being associated with a second component capable of providing a detectable signal in response to the binding or interaction of the poiypeptide or polynucleotide with the compound, and determining whether the compound binds to or otherwise interacts with and activates or inhibits an activity of the polypetide or polynucleotide bv detecting the presence or absence oi a signal generated from the binding or interaction of the compound with the poiypeptide or polynucleotide In accordance with yet another aspect of the invention, there are provided gluS agonists and antagonists, preferably bacteπostatic or bacteπocidal agonists and antagonists In a further aspect of the invention there are provided compositions compπsing a gluS polynucleotide or a gluS poiypeptide for administration to a cell or to a multicellular organism Vaπous changes and modifications within the spiπt and scope of the disclosed invention will become readily apparent to those skilled in the art from reading the following descπptions and from reading the other parts of the present disclosure GLOSSARY The following definitions are provided to facilitate understanding of certain terms used frequently herein "Host cell" is a cell which has been transformed or transfected, or is capable of transformation or transfection by an exogenous polynucleotide sequence Identit \ . as known in the art. is a relationship between two or more poiypeptide sequences or two or more polynucleotide sequences, as determined b\ compaπng the sequences In the art. identity also means the degree of sequence relatedness between poiypeptide or polynucleotide sequences, as the case may be, as determined by the match between stπngs of such sequences "Identity' and "similaπty" can be readily calculated bv known methods, including but not limited to those described in (Computational Molecular Biology, Lesk, A M , ed , Oxford University Press, New York, 1988. Biocomputing Informatics and Genome Projects, Smith, D W , ed . Academic Press. New York, 1993 Computer Analvsis of Sequence Data. Part I, Griffin, A M . and Griffin. H G . eds . Humana Press. New Jersey 1994. Sequence Analxsis in Molecular Bιolog\ v on Heinie. G Academic Press, 1987 and Sequence Anansi Primer, Gπbskov M and Devereux. J , eds . M Stockton Press. New York. 1991. and Caπllo, H , and Lip an. D , SIAM J Applied Math , 48 1073 ( 1988 ) Preferred methods to determine identity are designed to give the largest match between the sequences tested Methods to determine identity and similarity are codified in publicK available computer programs Preferred computer program methods to determine identity and similantv between two sequences include, but are not limited to. the GCG program package (Devereux, J . et al , Nucleic Acids Research 12(1) 387 ( 1984)), BLASTP, BLASTN. and FASTA f Atschul. S F et al . J Molec Bwl 215 403-410 ( 1990) The BLAST X program is publicly available from NCBI and other sources (BLAST Manual. Altschul. S . et al . NCBI NLM NTH Bethesda. MD 20894. Altschul. S . et al , J Mol Biol 215 403-410 ( 1990) As an illustration, by a polynucleotide having a nucleotide sequence having at least, for example, 95 "identity' to a reference nucleotide sequence of SEQ ID NO 1 it is intended that the nucleotide sequence of the polynucleotide is identical to the reference sequence except that the polynucleotide sequence may include up to five point mutations per each 100 nucleotides of the reference nucleotide sequence of SEQ ID NO 1 In other words, to obtain a polynucleotide having a nucleotide sequence at least 95% identical to a reference nucleotide sequence, up to 5% of the nucleotides in the reference sequence may be deleted or substituted with another nucleotide, or a number of nucleotides up to 5% of the total nucleotides in the reference sequence may be inserted into the reference sequence. These mutations of the reference sequence may occur at the 5 or 3 terminal positions of the reference nucleotide sequence or anywhere between those terminal positions, interspersed either individually among nucleotides in the reference sequence or in one or more contiguous groups within the reference sequence Analogously , by a poiypeptide having an amino acid sequence having at least, for example, 95% identity to a reference amino acid sequence of SEQ ID NO 2 is intended that the amino acid sequence of the poiypeptide is identical to the reference sequence except that the poiypeptide sequence may include up to five amino acid alterations per each 100 amino acids of the reference am o acid of SEQ ID NO 2 In other words, to obtain a poiypeptide having an ammo acid sequence at least 95% identical to a reference amino acid sequence, up to 5% of the amino acid residues in the reference sequence may be deleted or substituted with another amino acid, or a number of amino acids up to 5% of the total amino acid residues in the reference sequence mav be inserted into the reference sequence These alterations of the reference sequence mav occur at the amino or carboxy terminal positions of the reference amino acid sequence or anvwhere between those terminal positions, interspersed either individualK among residues in the reference sequence or in one or more contiguous groups within the reference sequence "Isolated" means altered "by the hand of man ' from its natural state, i e , if it occurs in nature, it has been changed or removed from its oπginal environment, or both For example, a polynucleotide or a poiypeptide naturally present in a living organism is not "isolated," but the same polynucleotide or poiypeptide separated from the coexisting mateπals of its natural state is "isolated", as the term is employed herein "Polynucleotιde(s) generalK refers to an> polyπbonucleotide or polydeoxπbonucleotide. which may be unmodified RNA or DNA or modified RNA or DNA "PolynucleotidefsV include, without limitation, single- and double-stranded DNA. DNA that is a mixture of single- and double-stranded regions or single-, double- and tπple-stranded regions sinele- and double-stranded RNA, and RNA that is mixture of smale- and double-stranded regions, hybπd molecules compπsing DNA and RNA that may be single-stranded or. more typically, double-stranded, or tπple-stranded regions, or a mixture of single- and double-stranded regions In addition, "polynucleotide" as used herein refers to tπple-stranded regions compπsing RNA or DNA or both RNA and DNA The strands in such regions may be from the same molecule or from different molecules The regions may include all of one or more of the molecules, but more typically involve only a region of some of the molecules One of the molecules of a tπple-hehcal region often is an o gonucleotide As used herein, the term "polynucleotide.s)" also includes DNAs or RNAs as descπbed above that contain one or more modified bases Thus, DNAs or RNAs with backbones modified for stability or for other reasons are "polynucleotιde(s)" as that term is intended herein Moreover, DNAs or RNAs compπsing unusual bases, such as mosine, or modified bases, such as tπtylated bases, to name just two examples, are polynucleotides as the term is used herein It will be appreciated that a great vaπety of modifications have been made to DNA and RNA that serve many useful purposes known to those of skill in the art The term polynucleotιde(s)" as it is employed herein embraces such chemically, enzymatically or metabolicalK modified forms of polynucleotides. as well as the chemical forms of DNA and RNA characteπstic of viruses and cells, including, for example, simple and complex cells "Polynucleotιde(s)" also embraces short polynucleotides often referred to as ohgonucleotιde(s) "Polypeptιde(s)" refers to any peptide or protein compπsing two or more amino acids joined to each other by peptide bonds or modified peptide bonds "Polypeptιde(s)" refers to both short chains, commonly referred to as peptides. o gopeptides and o gomers and to longer chains generalK referred to as proteins Polypeptides mav contain amino acids other than the 20 gene encoded amino acids "Polypeptιde(s)" include those modified either by natural processes, such _5 processing and other post-translational modifications, but also by chemical modification techniques Such modifications are well descπbed in basic texts and in more detailed monographs, as well as in a voluminous research literature, and they are well known to those of skill in the art It will be appreciated that the same type of modification may be present in the same or varying degree at several sites in a given poiypeptide Also, a given poiypeptide may contain many types of modifications Modifications can occur anywhere in a poiypeptide. including the peptide backbone, the amino acid side-chains, and the amino or carboxyl termini Modifications include, for example, acetylation. acvlation. ADP-πbosylation. amidation. covalent attachment of flavin, covalent attachment of a heme moietv . covalent attachment of a nucleotide or nucleotide deπvative. covalent attachment of a lipid or lipid deπvative. covalent attachment of phosphotidy nositol. cross-linking, cvc zation. disulfide bond formation, demethvlation. tormauon of covalent cross-links, tormauon of cysteine. formation of pyroglutamate. formylation. gamma-carboxylation, giycosylation. GPI anchor formation, hydroxylation. lodination. methylation. myπstoylation. oxidation, proteolytic processing, phosphorylation. prenylation, racemization, giycosylation, lipid attachment, sulfation, gamma- carboxylation of glutamic acid residues, hydroxylation and ADP-πbosylation. selenoylation. sulfation. transfer-RNA mediated addition of ammo acids to proteins, such as arginylation, and ubiquitmation See, for instance. PROTEINS - STRUCTURE AND MOLECULAR PROPERTIES. 2nd Ed., T E Creighton. W H. Freeman and Company. New York ( 1993) and Wold, F , Posttranslational Protein Modifications Perspectives and Prospects, pgs 1-12 in POSTTRANSLATIONAL COVALENT MODIFICATION OF PROTEINS, B C. Johnson, Ed., Academic Press, New York (1983), Seifter et al., Meth. Enzymol 182:626-646 (1990) and Rattan et al , Protein Svnthesis' Posttranslational Modifications and Aging, Ann. N Y Acad Sci 663 48-62 ( 1992) Polypeptides may be branched or cyclic, with or without branching Cyclic, branched and branched circular polypeptides may result from post-translational natural processes and may be made by entirely synthetic methods, as well "Vaπant(s)" as the term is used herein, is a polynucleotide or poiypeptide that differs from a reference polynucleotide or poiypeptide respectively, but retains essential properties A typical vaπant of a polynucleotide differs in nucleotide sequence from another, reference polynucleotide Changes in the nucleotide sequence of the variant may or may not alter the amino acid sequence of a poiypeptide encoded by the reference polynucleotide Nucleotide changes mav result in amino acid substitutions, additions, deletions, fusions and truncations in the poiypeptide encoded bv the reference sequence, as discussed below A typical vaπant ot a poiypeptide differs in amino acid sequence from another, reference poiypeptide Generally, differences are limited so that the sequences of the reference poiypeptide and the vaπant are closely similar overall and, in many regions, identical. A vaπant and reference poiypeptide may differ in amino acid sequence by one or more substitutions, additions, deletions in any combination A substituted or inserted amino acid residue may or may not be one encoded bv the genetic code A ariant of a polynucleotide or poiypeptide may be a naturally occurπng such as an allelic vaπant. or it may be a variant that is not known to occur naturallv Non-naturally occurπng variants of polynucleotides and polypeptides may be made bv mutagenesis techniques, by direct synthesis, and by other recombinant methods known to skilled artisans DESCRIPTION OF THE INVENTION The invention relates to novel gluS polypeptides and polynucleotides as described in greater detail below. In particular, the invention relates to polypeptides and polynucleotides of a novel gluS of Streptococcus pneumoniae. which is related by amino acid sequence homology to Bacillus subtilis glutamyl tRNA synthetase poiypeptide. The invention relates especially to gluS having the nucleotide and amino acid sequences set out in Table 1 [SEQ ID NO: 1 ] and Table 1 [SEQ ID NO: 2] respectively, and to the gluS nucleotide sequences of the DNA in the deposited strain and amino acid sequences encoded thereby. TABLE 1 gluS Polynucleotide and Poiypeptide Sequences (A) Streptococcus pneumoniae gluS polynucleotide sequence. [SEQ ID NO: 1 ] 5 ' - 1 GTACGTTACG CACCAAGTCC AACAGGACTA CTACACATCG GAAATGCCCG 51 7ACAGCATTG TTTAACTACT TGTATGCGC3 CCATCATGGT GGAACATTTC 101 TCATCCGTAT CGAAGATACT GACCGTAAAC GCCATGTCGA GGATGGTGAA 151 CGTTCACAAC TTGAAAACCT TCGCTGGTT GGCATGGATT GGGATGAAAG 201 TCCAGAATCA CATGAGAATT ATCGCCAGTC TGAGCGTTTG GACTTGTATC 251 AAAAATACAT TGACCAACTA TTAGCTGAAG GAAAAGCCTA TAAATCTTAC 301 GTTACAGAAG AAGAGTTGGC AGCTGAACGT GAACGTCAAG AAGCTGCTGG 351 TGAAACACCT CGATATATCA ACGAATACCT TGGTATGAGT GAAGAGGAAA 401 AAGCGGCTTA TATCGCAGAA CGTGAAGCAG CTGGTATCAT ACCAACAGTT 451 CGTTTGGCTG TCAATGAGTC AGGTATCTAC AAGTGGCATG ATATGGTCAA 501 AGGTGATATC GAATTTGAAG GTGGCAATAT CGGCGGTGAC TGGGTTATCC 551 AAAAGAAAGA CGGTTACCCA ACTTACAACT TTGCCGTTGT TATCGATGAC 601 CACGATATGC AAATCTCTCA TGTTATCCGT GGAGATGACC ATATTGCTAA 651 TACACCAAAA CAGCTTATGG TCTATGAAGC TCTTGGTTGG GAAGCTCCAG 7C1 AGTTTGGTCA CATGACCTTG ATTATCAACT CTGAGACTGG TAAGAAGTTA 751 TCTAAACGTG ATACTAATAC ACTTCAATTT ATCGAAGATT ACCGAAAGAA 801 AGGTTACCTT CCAGAAGCAG TCTTTAACTT TATTGCTCTT CTTGGTTGGA 851 ACCCAGGTGG TGAAGATGAG ATTTTCTCTC GTGAAGAACT CATTAAACTT 901 TTTGATGAAA ACCGCCTCAG CAAGTCACCA GCAGCCTTTG ATCAGAAAAA 951 ACTAGACTGG ATGAGCAATG ATTATATCAA GAATGCAGAC CTTGAAACCA 1001 TCTTTGAAAT GGCAAAACCA TTCTTAGAGG AAGCAGGccg ccgaccgac 1051 aaggctgaaa aattATTCGA TCTCTATAAA CCACAAATGA AATCAGTAGA 1101 TGAGATTATC CCATTGACAG ATCTTTTCTT CTCAGATTTC CCAGAATTGA 1151 CAGAAGCAGA GCGCGAAGTC ATGACGGGTG AAACAGTTCC AACAGTTCTT 1201 GAAGCATTCA AAGCAAAACT TGAAGCGATG ACAGATGATG AATTTGTGAC 1251 AGAAAATATC TTCCCGCAAA TTAAAGCAGT CCAAAAAGAA ACAGGTATTA 1301 AAGGGAAAAA TCTTTTCATG CCTATTCGTA TCGCAGTTTC AGGCGAAATG 1351 CATGGGCCAG AATTACCAGA TACAATTTTC TTGCTTGGAC GTGAAAAATC 1401 AATTCAGCAT ATCGAAAACA TTCTAAAAGA AATCTCTAAA TAA-3 ' (B) gluS poiypeptide sequence deduced from the polynucleotide sequence in this table. [SEQ ID NO:2] NH 2 -1 VRYAPSPTGL KIGNARTA FIJYLYARHKG GTFLIRIEDT DRKRKVEDGE 51 RSQLEN RW GMDWDESPE3 HENYRQSER YQKYISQL AΞGKAYKSY 101 VTEEELAAER ERQEAAGET? RYINEY G Ξ ΞEΞKAAYIAΞ REAAGIIPTV 151 RLAVNESGIY KWHDMVKGDI EFEGGNIGGD VIQKKDGYP TYNFAWIDD 201 HDMQIΞHVIR GDDHIANTPK QLMVYEA GV. EAPEFGHKT IINSETGKKL 251 SKRDTNTLQF IΞDYRKKGY__ PEAVFNFIA GWNPGGEDΞ IFΞREELIK 301 FDENRLSKS? AAFDQKKLDV.' MΞNDYIKNAD ΞTIFEIAKP F1ΞEAGRLTD 351 MAEK FDLY PQMKSVDΞII P TDLFF3DF PΞI EAΞRΞV TGETVPTVL 4C1 ΞAFKAK EA;-: T__OEFVTE..: FPQI AVQKΞ TGIKGKΠLF PIRIAVΞGE:-. 451 HGPELPDTIF LLGREKΞIQH IENILKΞIΞK-COOH (C) Polynucleotide sequence embodιment[SEQ ID NO: 1 ] x_(R l ) m" 1 GTACGTTACG CACCAAGTCC AACAGGACTA CTACACATCG GAAATGCCCG 51 TACAGCATTG TTTAACTACT TGTATGCGCG CCATCATGGT GGAACATTTC 101 TCATCCGTAT CGAAGATACT GACCGTAAAC GCCATGTCGA GGATGGTGAA 151 CGTTCACAAC TTGAAAACCT TCGCTGGTTA GGCATGGATT GGGATGAAAG 2C1 TCCAGAATCA CATGAGAA T ATCGCCAGTC TGAGCGTTTG GACTTGTATC 251 AAAAATACAT TGACCAACTA TTAGCTGAAG GAAAAGCCTA TAAATCTTAC 301 GTTACAGAAG AAGAGTTGGC AGCTGAACGT GAACGTCAAG AAGCTGCTGG 351 TGAAACACCT CGATATATCA ACGAATACCT TGGTATGAGT GAAGAGGAAA 401 AAGCGGCTTA TATCGCAGAA CGTGAAGCAG CTGGTATCAT ACCAACAGTT 451 CGTTTGGCTG TCAATGAGTC AGGTATCTAC AAGTGGCATG ATATGGTCAA 501 AGGTGATATC GAATTTGAAG GTGGCAATAT CGGCGGTGAC TGGGTTATCC 551 AAAAGAAAGA CGGTTACCCA ACTTACAACT TTGCCGTTGT TATCGATGAC 601 CACGATATGC AAATCTCTCA TGTTATCCGT GGAGATGACC ATATTGCTAA 651 TACACCAAAA CAGCTTATGG TCTATGAAGC TCTTGGTTGG GAAGCTCCAG 701 AGTTTGGTCA CATGACCTTG ATTATCAACT CTGAGACTGG TAAGAAGTTA 751 TCTAAACGTG ATACTAATAC ACTTCAATTT ATCGAAGATT ACCGAAAGAA 801 AGGTTACCTT CCAGAAGCAG TCTTTAACTT TATTGCTCTT CTTGGTTGGA 851 ACCCAGGTGG TGAAGATGAG ATTTTCTCTC GTGAAGAACT CATTAAACTT 901 TTTGATGAAA ACCGCCTCAG CAAGTCACCA GCAGCCTTTG ATCAGAAAAA 951 ACTAGACTGG ATGAGCAATG ATTATATCAA GAATGCAGAC CTTGAAACCA 1001 TCTTTGAAAT GGCAAAACCA TTCTTAGAGG AAGCAGGccg _rtgactgac 1051 aaggctgaaa aattATTCGA TCTCTATAAA CCACAAATGA AATCAGTAGA 1101 TGAGATTATC CCATTGACAG ATCTTTTCTT CTCAGATTTC CCAGAATTGA 1151 CAGAAGCAGA GCGCGAAGTC ATGACGGGTG AAACAGTTCC AACAGTTCTT 1201 GAAGCATTCA AAGCAAAACT TGAAGCGATG ACAGATGATG AATTTGTGAC 1251 AGAAAATATC TTCCCGCAAA TTAAAGCAGT CCAAAAAGAA ACAGGTATTA 1301 AAGGGAAAAA TCTTTTCATG CCTATTCGTA TCGCAGTTTC AGGCGAAATG 1351 CATGGGCCAG AATTACCAGA TACAATTTTC TGCTTGGAC GTGAAAAATC 1401 AATTCAGCAT ATCGAAAACA TTCTAAAAGA AATCTCTAAA TAA-(R.2) n -Y (D) Poiypeptide sequence embodiment [SEQ ID NO.2] X- (R 1 ) m - , /RYAPSPTG__ LHIGNARTAL FNY YARHHG GTFLIRIEDT DRKRHVEDGE 51 RSQLENLRWL GMDWDESPΞ5 HENYRQSERL DLYQKYIDQL LAEGKAYKΞY 101 YTEEELAAER ERQEAAGET? RYINEYLG..S ΞEEKAAYIAE RΞAAGIIPTV 151 RLAVNESGIY KWHDMVKGDI EFEGGNIGGD WVIQKKDGYP TYNFAWIDD 201 HDMQISKVIR GDDHIANT?" QLMVYEALG.: EAPEFGHMTL IINSETGKKL 251 3KRDTNTLQF IΞDYRKKGYL PEAVFNFIAL LGWNPGGEDΞ IFSREELIKL 301 FOENRLSKS? AAFDQKKLDV. MSNDYIKNAD LETIFEMAKP FLEEAGRLTD 351 KAΞKLFDLYK PQMKSVDEII PLTDLFFSDF PΞLTΞAEREV MTGETVPTVL 401 EAFKAKLEAM TDDΞFVTENI FPQIKAVQKE TGIKGKNLFM PIRIAVSGEM 451 HGPELPDTIF LLGREKΞIQH IENILKΞIΞK- (R 2 ) n -Y Deposited materials A deposit containing a Streptococcus pneumoniae 0100993 strain has been deposited with the National Collections of Industπal and Maπne Bacteπa Ltd ( herein 'NCIMB"), 23 St Machar Dπve, Aberdeen AB2 IRY. Scotland on 1 1 Apπl 1996 and assigned deposit number 40794 The deposit was descπbed as Streptococcus pneumoniae 0100993 on deposit On 17 Apπl 1996 a Streptococcus pneumoniae 0100993 DNA library in E. coli was similarly depositedwith the NCIMB and assigned deposit number 40800 The Streptococcus pneumoniae strain deposit is referred to herein as "the deposited strain" or as "the DNA of the deposited strain " The deposited strain contains the full length gluS gene The sequence of the polynucleotides contained in the deposited strain, as well as the amino acid sequence of the poiypeptide encoded thereby, are controlling in the event of any conflict with any descπption of sequences herein The deposit of the deposited strain has been made under the terms of the Budapest Treaty on the Intemationai Recognition of the Deposit of Micro-organisms for Purposes of Patent Procedure The strain will be irrevocably and without restnction or condition released to the public upon the issuance of a patent The deposited strain is provided merely as convenience to those of skill in the an and is not an admission that a deposit is required for enablement. such as that required under 35 U S C § 1 12 A license may be required to make, use or sell the deposited strain, and compounds deπved therefrom, and no such license is hereby granted Polypeptides The polypeptides of the invention include a poiypeptide of Table 1 [SEQ ID NO 2] (in particular the mamre poiypeptide) as well as poK peptides and fragments, particularly those which have the biological activity of gluS. and also those which have at least 707c identity to a poiypeptide of Table 1 [SEQ ID NO 2] or the relevant portion, preferablv at least 807c identity to a poiypeptide of Table 1 [SEQ ID NO 2], and more preferably at least 90% similaπtv (more preferably at least 90%- identity) to a poiypeptide of Table 1 [SEQ ED NO 2] and still more preferably at least 957c similaπty (still more preferabK at least 95% identity) to a poiypeptide of Table 1 [SEQ ID NO 2] and also include portions of such polypeptides with such portion of the poiypeptide generally containing at least 30 ammo acids and more preferably at least 50 amino acids The invention also includes polypeptides of the formula set forth in Table 1 (D) wherein, at the amino terminus. X is hydrogen, and at the carboxyl terminus. Y is hydrogen or a metal, R j and Ro is amino acid residue, m is an integer between 1 and 1000 or zero, and n is an integer between 1 and 1000 or zero Any stretch of amino acid residues denoted by either R group, where n and/or m is an integer greater than 1 , may be either a heteropolymer or a homopolymer. preferably a heteropolymer Other preferred embodiments provide polypeptides where n is zero and m is the integer 1, 2. 3, 4, 5, 6, 7, 8, 9, or 10 In such preferred embodiments it is most preferred that the amino terminal amino acid residue is a methionyl residue A fragment is a vaπant poiypeptide having an amino acid sequence that entirely is the same as part but not all of the amino acid sequence of the aforementioned polypeptides As with gluS polypeptides fragments may be free-standing, or compπsed within a larger poiypeptide ot which thev form a part or region, most preferably as a single continuous region, a single larger poiypeptide Preferred fragments include, for example, truncation polypeptides having a portion of the amino acid sequence of Table 1 [SEQ ID NO.2], or of vaπants thereof, such as a continuous seπes of residues that includes the amino terminus, or a continuous seπes of residues that includes the carboxyl terminus Degradation forms of the polypeptides of the invention in a host cell, particularly a Streptococcus pneumoniae. are also preferred Further preferred aie fragments characteπzed bv structural or functional attπbutes such as fragments that compπse alpha-helix and alpha-helix forming regions, beta-sheet and beta-sheet-forming regions, turn and tum- forming regions, coil and coil-forming regions, hvdrophi c regions, hv dropnooic regions, alpha amphipathic regions, beta amphipathic regions, flexible regions surface-forming regions. substrate binding region, and high antigenic index regions Also preferred are biologically active fragments which are those fragments that mediate activities of gluS. including those with a similar activity or an improved activity, or with a decreased undesirable activity Also included are those fragments that are antigenic or lmmunogenic in an animal, especially in a human Particularlv preferred are fragments compπsing receptors or domains of enzymes that confer a runction essential for viabilitv of Streptococcus pneumoniae or the ability to initiate, or maintain cause disease in an individual, particularly a human Vaπants that are fragments of the polypeptides of the invention may be employed for producing the corresponding full-length poiypeptide bv peptide sv nthesis. therefore, these vanants may be employed as intermediates for producing the full-length polypeptides of the invention Polynucleotides Another aspect of the invention relates to isolated polynucleotides that encode the gluS poiypeptide having the deduced amino acid sequence of Table 1 [SEQ ED NO.2] and polynucleotides closely related thereto and vaπants thereof Using the information provided herein, such as a polynucleotide sequence set out in Table 1 [SEQ ID NO 1 ], a polynucleotide of the invention encoding gluS poiypeptide may be obtained using standard cloning and screening methods, such as those for cloning and sequencing chromosomal DNA fragments from bacteπa using Streptococcus pneumoniae 0100993 cells as starting mateπal, followed by obtaining a full length clone For example, to obtain a polynucleotide sequence of the invention, such as the full length gene sequence given in Table 1 [SEQ ID NO 1 ], typically a library of clones of chromosomal DNA of Streptococcus pneumoniae 0100993 in E coli or some other suitable host is probed with a radiolabeled ohgonucleotide, preferably a 17-mer or longer, deπved from a partial sequence Clones carrying DNA identical to that of the probe can then be distinguished using stringent conditions By sequencing the individual clones thus identified with sequencing pπmers designed from the original sequence it is then possible to extend the sequence in both directions to determine the full gene sequence Conveniently, such sequencing is performed using denatured double stranded DNA prepared from a plasmid clone Suitable techniques are descπbed by Maniatis, T . Fπtsch, E F and Sambrook et al , MOLECULAR CLONING. A LABORATORY MANUAL. 2nd Ed . Cold Spπng Harbor Laboratory Press. Cold Spπng Harbor. New York ( 1989) ( see in paπicular Screening Bv Hybridization 1 90 and Sequencing Denatured Double-Stranded DNA Templates 13 70) Illustrative of the invention, the polynucleotide set out in Table 1 [SEQ ED NO 1 ] was discovered in a DNA library deπved from Streptococcus pneumoniae 0100993 The stop codon of the polyncleotide sequence of Table 1 (A) is underlined The DNA sequence set out in Table 1 [ SEQ ID NO 1 ] contains an open reading frame encoding a protein having about the number of amino acid residues set forth in Table 1 [SEQ ID NO.2 respectively] with a deduced molecular weight that can be calculated using amino acid residue molecular weight values well known in the art gluS of the invention is structurally related to other proteins of the glutamyl tRNA synthetase family, as shown by the results of sequencing the DNA encoding gluS of the deposited strain The protein exhibits greatest homology to Bacillus subtilis glutamyl tRNA synthetase protein among kno n proteins The invention provides a polynucleotide sequence identical over its entire length to the coding sequence in Table 1 [SEQ ED NO 1 ] Also provided by the invention is the coding sequence for the mature poiypeptide or a fragment thereof, by itself as well as the coding sequence for the mature poiypeptide or a fragment in reading frame with other coding sequence, such as those encoding a leader or secretory sequence, a pre-, or pro- or prepro- protein sequence The polynucleotide may also contain non-coding sequences, including for example, but not limited to non-coding 5' and 3' sequences, such as the transcπbed. non-translated sequences termination signals, πbosome binding sites, sequences that stabilize mRNA. introns. polyadenylation signals, and additional coding sequence which encode additional ammo acids For example, a marker sequence that facilitates puπfication of the fused poiypeptide can be encoded In certain embodiments of the invention, the marker sequence is a hexa-histidine peptide. as provided in the pQE vector (Qiagen, Inc ) and descπbed in Gentz et al . Proc Natl Acad Sci USA 86 821-824 ( 1989). or an HA tag (Wilson et al , Cell 37 767 ( 1984) Polvnucleotides ot the invention also include, but are not limited to. polynucleotides compπsing a structural gene and its naturally associated sequences that control gene expression A preferred embodiment of the invention is the polynucleotide compπsing a nucleotide sequence set forth in SEQ ED NO. l of Table 1 which encodes the gluS poiypeptide The invention also includes polynucleotides of the formula set forth in Table 1 (C) wherein, at the 5' end of the molecule, X is hydrogen, and at the 3' end of the molecule. Y is hydrogen or a metal, R [ and R is anv nucleic acid residue, m is an integer between 1 and 1000 or zero, and n is an integer between 1 and 1000 or zero Anv stretch of nucleic acid residues denoted bv either R group, where n an or m is an integer greater than 1 mav be either a heteropolvmer or a homopolymer, preferably a heteropolvmer Other preferred embodiments provide polynucleotides where n is zero and m is the integer 3 6, 9, 12. 15, 18, 21, 24. 27 or 30 In such preferred embodiments it is most preferred that the 5 terminal nucleic acid residues be ATG or GTG or encode a methionine The term "polynucleotide encoding a poiypeptide as used herein encompasses polynucleotides that include a sequence encoding a poiypeptide of the invention, particularly a bacteπal poiypeptide and more particularlv a poiypeptide of the Streptococcus pneumoniae gluS having the amino acid sequence set out in Table 1 [SEQ ED NO 2] The term also encompasses polynucleotides that include a single continuous region or discontinuous regions encoding the poiypeptide (for example, interrupted bv integrated phage or an insemon sequence or editing) together with additional regions, that also may contain coding and/or non-coding sequences The invention further relates to vaπants of the polynucleotides descπbed herein that encode for vaπants of the poiypeptide having the deduced amino acid sequence of Table 1 [SEQ ED NO.2] Vaπants that are fragments of the polynucleotides of the invention may be used to synthesize full-length polynucleotides of the invention Further particularly preferred embodiments are polynucleotides encoding gluS vaπants. that have an amino acid sequence of gluS poiypeptide of Table 1 [SEQ ED NO 2] in which several, a few. 5 to 10, 1 to 5, 1 to 3, 2, 1 or no amino acid residues are substituted, deleted or added, in any combination Especially preferred among these are silent substitutions, additions and deletions, that do not alter the properties and activities of gluS Further preferred embodiments of the invention are polynucleotides that are at least 707c identical over their entire length to a polynucleotide encoding gluS poiypeptide having an ammo acid sequence set out in Table 1 [SEQ ID NO.2], and polynucleotides that are complementary to such polynucleotides Alternatively, most highly preferred are polynucleotides that compπse a region that is at least 807c identical over its entire length to a polynucleotide encoding gluS poiypeptide of the deposited strain and polynucleotides complementary thereto In this regard, polynucleotides at least 907c identical over their entire length to the same are particularly preferred, and among these particularly preferred polynucleotides. those with at least 957c are especially preferred. Furthermore, those with at least 977c are highly preferred among those with at least 957c, and among these those with at least 987c and at least 997c are particularly highly preferred, with at least 997c being the more preferred Preferred embodiments are polynucleotides that encode polypeptides that retain substantially the same biological function or activ ity as the mature poiypeptide encoded by a DNA of Table 1 [SEQ ED NO 1 ] The invention further relates to polynucleotides that hybπdize to the herein above- descπbed sequences In this regard, the invention especially relates to polynucleotides that hybπdize under stπngent conditions to the herein above-descπbed polynucleotides As herein used, the terms stπngent conditions' and "stπngent hybπdization conditions' mean hybπdization will occur only if there is at least 957c and preferably at least 977c identity between the sequences An example of stringent hybridization conditions is overnight incubation at 42°C in a solution comprising 507c formamide. 5x SSC ( 150mM NaCl. 15mM tπsodium citrate). 50 mM sodium phosphate (pH7 6). 5x Denhardt s solution. 107c dextran sulfate. and 20 micrograms/ml denatured, sheared salmon sperm DNA. followed by washing the hybridization support in 0 l x SSC at about 65°C Hybridization and wash conditions are well known and exemplified in Sambrook. et al.. Molecular Cloning. A Laboratory Manual, Second Edition. Cold Spring Harbor. N Y . ( 1989). particularly Chapter 1 1 therein The invention also provides a polynucleotide consisting essentially of a polynucleotide sequence obtainable by screening an appropπate library containing the complete gene for a polynucleotide sequence set forth in SEQ ID NO.1 under stringent hybπdization conditions with a probe having the sequence of said polynucleotide sequence set forth in SEQ ID NO. l , 3, 5, respectively or a fragment thereof, and isolating said DNA sequence Fragments useful for obtaining such a polynucleotide include, for example, probes and pπmers descπbed elsewhere herein As discussed additionally herein regarding polynucleotide assays of the invention, for instance, polynucleotides of the invention as discussed above, may be used as a hybπdization probe for RNA, cDNA and genomic DNA to isolate full-length cDNAs and genomic clones encoding gluS and to isolate cDNA and genomic clones of other genes that ha e a high sequence similanty to the gluS gene Such probes generally will compnse at least 15 bases Preferably. such probes will have at least 30 bases and may have at least 50 bases Particularly preferred probes will have at least 30 bases and will have 50 bases or less For example, the coding region of the gluS gene may be isolated by screening using a DNA sequence provided in SEQ ED NO 1 to synthesize an o gonucleotide probe A labeled o gonucleotide having a sequence complementary to that of a gene of the invention is then used to screen a library of cDNA, genomic DNA or mRNA to determine which members of the library the probe hybπdizes to The polynucleotides and polypeptides of the invention mav be employed, for example as research reagents and mateπais for discovery ot treatments of and diagnostics for disease particularly human disease, as further discussed herein relating to polynucleotide assays Polynucleotides of the invention that are o gonucleotides derived from the sequences of SEQ ID NOS. 1 and/or 2 and/or 3 and/or 4 may be used in the processes herein as described, but preferably for PCR, to determine whether or not the polynucleotides identified herein in whole or in part are transcribed in bacteria in infected tissue It is recognized that such sequences will also have utility in diagnosis of the stage of infection and type ot infection the pathogen has attained The invention also provides polv nucleotides that mav encode a poiypeptide that is the mature protein plus additional amino or carboxyl-terminal amino acids, or amino acids inteπor to the mamre poiypeptide (when the mature form has more than one poiypeptide chain, for instance ) Such sequences may play a role in processing of a protein from precursor to a mature form, may allow protein transport, may lengthen or shorten protein half-life or may facilitate manipulation of a protein for assay or production, among other things As generally is the case in vivo, the additional amino acids may be processed away from the mature protein by cellular enzymes A precursor protem. having the mature form of the poiypeptide fused to one or more prosequences may be an inactive form of the poiypeptide When prosequences are removed such inactive precursors generally are activated Some or all of the prosequences may be removed before activation Generally, such precursors are called proproteins In sum. a polynucleotide of the invention may encode a mamre protein, a mamre protein plus a leader sequence (which may be referred to as a preprotein), a precursor of a mamre protein having one or more prosequences that are not the leader sequences of a preprotein, or a preproprotein. which is a precursor to a proprotein. having a leader sequence and one or more prosequences. which generally are removed duπng processing steps that produce active and mamre forms of the poiypeptide Vectors, host cells, expression The invention also relates to vectors that compnse a polynucleotide or polynucleotides of the invention, host cells that are genetically engineered with vectors of the invention and the production of polypeptides of the invention by recombinant techniques Cell-free translation systems can also be employed to produce such proteins using RNAs deπved from the DNA constructs of the invention For recombinant production, host cells can be genetically engineered to incorporate expression systems or portions thereof or polynucleotides of the invention Introduction ot a polynucleotide into the host cell can be effected bv methods descnbed in many standard laboratory manuals, such as Davis et al , BASIC METHODS IN MOLECL LAR BIOLOGY, ( 1986) and Sambrook et al., MOLECULAR CLONING A LABORATORY MANUAL, 2nd Ed , Cold Spnng Harbor Laboratory Press, Cold Spπng Harbor, N Y (1989), such as, calcium phosphate transfection, DEAE-dextran mediated transfection. transvection. microinjection. cationic pid-mediated transfection. electroporation. transduction. scrape loading, ballistic introduction and infection Representative examples of appropπate hosts include bactenal cells, such as streptococci, staphylococci enterococci E toll, streptomvces and Bacillus suotihs cells, fungal cells, such as east cells and Aspergdlus cells, insect cells such as Drosophda S2 and Spodoptera Sf9 cells, animal cells such as CHO. COS. HeLa, C 127. 3T3. BHK. 293 and Bowes melanoma cells, and plant cells A great vaπety of expression systems can be used to produce the polypeptides of the invention Such vectors include, among others, cnromosomal. episomal and virus-deπved vectors, e g., vectors deπved from bacteπal plasmids. from bacteπophage, from transposons. from yeast episomes. from insertion elements, from yeast chromosomal elements, from viruses such as baculoviruses, papova viruses, such as SV40. vaccinia viruses, adenoviruses. fowl pox viruses, pseudorabies viruses and retroviruses. and vectors deπved from combinations thereof, such as those deπved from plasmid and bacteπophage genetic elements, such as cosmids and phagemids The expression system constructs may contain control regions that regulate as well as engender expression Generally, any system or vector suitable to maintain, propagate or express polynucleotides and/or to express a poiypeptide in a host may be used for expression in this regard The appropπate DNA sequence may be inserted into the expression system by any of a vaπety of well-known and routine techniques, such as, for example, those set forth in Sambrook et al . MOLECULAR CLONING. A LABORATORY MANUAL, (supra) For secretion of the translated protein into the lumen of the endoplasmic reticulum, into the peπplasmic space or into the extracellular environment, appropπate secretion signals may be incorporated into the expressed poiypeptide These signals may be endogenous to the poiypeptide or they may be heterologous signals Polypeptides of the invention can be recovered and puπfied from recombinant cell cultures by well-known methods including ammonium sulfate or ethanol precipitation, acid extraction, anion or cation exchange chromatography . phosphocellulose chromatography, hydrophobic interaction chromatography . affinity chromatographv . hydroxylapatite chromatographv and lectin chromatography Most preferabK high pertormance liquid chromatographv is employed for punfication Well known techniques tor refolding protein mav Iz employed to regenerate active conformation w hen the poiypeptide is denatured duπng isolation and or punfication Diagnostic Assays This invention is also related to the use of the gluS polynucleotides of the invention for use as diagnostic reagents Detection of gluS in a eukaryote. particularly a mammal, and especially a human, will provide a diagnostic method for diagnosis of a disease Eukaryotes (herein also ιndιvιdual(s)"), particularly mammals, and especially humans, infected with an organism compnsing the gluS gene may De detected at the nucleic acid lev el by a vaπety of techniques Nucleic acids for diagnosis may be obtained from an infected individual's cells and tissues, such as bone, blood, muscle, cartiiaee. and skin Genomic DNA mav be used directly for detection or may be amplified enzymatically by using PCR or other amplification technique pπor to analysis. RNA or cDNA may also be used in the same ways Using amplification, characteπzation of the species and strain of prokaryote present in an individual, may be made by an analysis of the genotype of the prokaryote gene. Deletions and insertions can be detected by a change in size of the amplified product in compaπson to the genotype of a reference sequence Point mutations can be identified by hybπdizmg amplified DNA to labeled gluS polynucleotide sequences Perfectly matched sequences can be distinguished from mismatched duplexes by RNase digestion or by differences in melting temperatures DNA sequence differences may also be detected by alterations in the electrophoretic mobility of the DNA fragments in gels, with or without denatuπng agents, or by direct DNA sequencmg See. e.g., Myers et al.. Science, 230: 1242 (1985) Sequence changes at specific locations also may be revealed by nuclease protection assays, such as RNase and S I protection or a chemical cleavage method See. e.g . Cotton et al . Proc Nad Acad Set . USA. 85 4397-4401 ( 1985) Cells carrying mutations or polymorphisms in tne gene of the inv ention may also be detected at the DNA level by a vaπety of techniques, to allow for serotyping. for example. For example, RT-PCR can be used to detect mutations It is particularly preferred to used RT-PCR in conjunction with automated detection systems, such as. for example. GeneScan RNA or cDNA may also be used for the same purpose, PCR or RT-PCR As an example, PCR pnmers complementary to a nucleic acid encoding gluS can be used to identify and analyze mutations The invention further provides these pnmers with 1, 2, 3 or 4 nucleotides removed from the 5' and or the 3' end These pnmers may be used for. among othe4r things, amplifying gluS DNA isolated from a sample denved from an individual The pnmers may be used to amplify the gene isolated from an infected individual such that the gene may then be subject to v anous techniques for elucidation of the DNA sequence In this way, mutations in the DNA sequence may be detected and used to diagnose infection and to serotype and/or classify the infectious agent The invention further provides a process for diagnosing, disease, preferably bacterial infections, more preferably infections by Streptococcus pneumoniae, and most preferably otitis media, conjunctivitis, pneumonia, bacteremia, meningitis, sinusitis, pleural empyema and endocarditis, and most particularly meningitis, such as for example infection of cerebrospinal fluid, compπsing determining from a sample derived from an individual a increased level of expression of polynucleotide having a sequence of Table 1 [SEQ ID NO 1 ] Increased or decreased expression of gluS polynucleotide can be measured using any on of the methods well known in the art for the quantation of polynucleotides, such as. for example. amplification, PCR. RT-PCR. RNase protection. Northern blotting and other hybπdization methods In addition, a diagnostic assay in accordance with the invention for detecting over- expression of gluS protein compared to normal control tissue samples may be used to detect the presence of an infection, for example Assay techniques that can be used to determine levels of a gluS protein, in a sample deπved from a host are well-known to those of skill in the art Such assay methods include radioimmunoassays, competitive-binding assays. Western Blot analysis and ELISA assays Antibodies The polypeptides of the invention or vaπants thereof, or cells expressing them can be used as an immunogen to produce antibodies immunospecific for such polypeptides "Antibodies" as used herein includes monoclonal and polyclonal antibodies, chimeπc. single chain, simianized antibodies and humanized antibodies, as well as Fab fragments, including the products of an Fab immunolglobulin expression library Antibodies generated against the polypeptides ot the invention can be obtained by administeπng the polypeptides or epitope-beaπng fragments, analogues or cells to an animal, preferably a nonhuman, using routine protocols For preparation of monoclonal antibodies, any technique known in the art that provides antibodies produced by continuous cell line cultures can be used Examples include vaπous techniques, such as those in Kohler, G and Milstein, C . Nature 256 495-497 ( 1975), Kozbor et al . Toda\ 4 72 ( 1983). Cole et al , pg 77- 96 in MONOCLONAL ANTIBODIES AND CANCER THERAPY. Alan R Liss. Inc (1985) Techniques for the production of single chain antibodies ( U S Patent No 4,946.778 ) can be adapted to produce single chain antibodies to polypeptides of this inv ention Also. transgenic mice, or other organisms such as other mammals, may be used to express humanized antibodies Alternatively phage display technology may be utilized to select antibody genes with binding activities towards the poiypeptide either from repertoires of PCR amplified v- genes of lymphocytes from humans screened for possessing anti-gluS or from naive libraries (McCafferty. J et al.. ( 1990). Nature 348. 552-554. Marks. J et al . ( 1992) Biotechnology 10. 779-783). The affinity of these antibodies can also be improved by chain shuffling (Clackson. T et al , ( 1991 . Nature 352. 624-628) If two antigen binding domains are present each domain mav be directed against a different epitope - termed bispecific antibodies The above-descπbed antibodies may be employed to isolate or to identify clones expressing the polypeptides to punfy the polypeptides by affinity chromatography Thus, among others, antibodies against gluS- poiypeptide may be employed to treat infections, particularly bacteπal infections and especially otitis media, conjunctivitis, pneumonia. bacteremia. meningitis, sinusitis, pleural empyema and endocarditis, and most particularly meningitis, such as for example infection of cerebrospinal fluid Poiypeptide vaπants include antigenically. epitopically or immunologically equivalent vaπants that form a particular aspect of this invention The term ' antigenically equivalent deπvative" as used herein encompasses a poiypeptide or its equivalent which will be specifically recognized by certain antibodies which, when raised to the protein or poiypeptide according to the invention, interfere with the immediate physical interaction between pathogen and mammalian host The term immunologically equivalent deπvative" as used herein encompasses a peptide or its equivalent which when used in a suitable formulation to raise antibodies in a vertebrate, the antibodies act to interfere with the immediate physical interaction between pathogen and mammalian host The poiypeptide. such as an antigenically or immunologically equivalent derivative or a fusion protein thereof is used as an antigen to immunize a mouse or other animal such as a rat or chicken The fusion protein may provide stability to the poiypeptide The antigen may be associated, for example by conjugation, with an lmmunogemc carrier protein for example bovine serum albumin (BSA) or keyhole limpet haemocvamn (KLH) AlternativeK a multiple antigenic peptide comprising multiple copies of the protein or poiypeptide. or an antigemcalK or immunologicallv equivalent poiypeptide thereof may be sufficiently antigenic to improv e immunogenicity so as to obviate the use of a earner Preferably, the antibody or vaπant thereof is modified to make it less lmmunogemc in the individual For example, if the individual is human the antibody may most preferably be "humanized", where the comphmentaπty determining regιon(s) of the hybπdoma-deπved antibody has been transplanted into a human monoclonal antibody , for example as described in Jones, P et al ( 1986), Nature 321 , 522-525 or Tempest et al.,( 1991 ) Biotechnology 9, 266-273 The use of a polynucleotide of the inv ention in genetic immunization will preferably employ a suitable delivery method such as direct miection of plasmid DNA into muscles (Wolff et al , Hum Mol Genet 1992. 1 363. Manthorpe et al , Hum Gene Ther 1963 4. 419). delivery of DNA complexed with specific protein earners (Wu et al . J Biol Chem 1989 264.16985 ). coprecipitauon of DNA with calcium phosphate (Benvenistv & Reshef. PNAS. 1986:83,9551 ), encapsulation of DNA in vaπous forms of hposomes (Kaneda et al.. Science 1989-243.375), panicle bombardment (Tang et al . Nature 1992, 356: 152. Eisenbraun et al., DNA Cell Biol 1993, 12.791 ) and in vivo infection using cloned retroviral vectors (Seeger et al., PNAS 1984:81.5849) Antagonists and agonists - assays and molecules Polypeptides of the invention may also be used to assess the binding of small molecule substrates and gands in. for example, cells, cell-free preparations, chemical hbranes. and natural product mixtures These substrates and hgands may be natural substrates and gands or may be structural or functional mimetics. See, e.g., Cohgan et al.. Current Protocols in Immunology 7(2): Chapter 5 (1991). The invention also provides a method of screening compounds to identify those which enhance (agonist) or block (antagonist) the action of gluS polypeptides or polynucleotides, particularly those compounds that are bacteπostatic and/or bacteπocidal The method of screening mav involve high-throughput techniques For example, to screen for agonists or antagoists. a synthetic reaction mix. a cellular compartment, such as a membrane, cell envelope or cell wall, or a preparation of any thereof, compnsing gluS poiypeptide and a labeled substrate or hgand of such poiypeptide is incubated in the absence or the presence of a candidate molecule that may be a gluS agonist or antagonist. The ability of the candidate molecule to agonize or antagonize the gluS poiypeptide is reflected in decreased binding of the labeled gand or decreased production of product from such substrate Molecules that bind gratuitously, ; e . without inducing the effects of gluS poiypeptide are most likely to be good antagonists Molecules that bind well and increase the rate ot product production from substrate are agonists Detection of the rate or level of production of product from substrate may be enhanced by using a importer system Reporter systems that may be useful in this regard include but are not limited to coloπmetπc labeled substrate converted into product, a reporter gene that is responsive to changes in gluS polynucleotide or poiypeptide activit , and binding assays known in the art. Another example of an assay for gluS antagonists is a competitive assay that combines gluS and a potential antagonist with gluS-binding molecules, recombinant gluS binding molecules, natural substrates or hgands. or substrate or hgand mimetics. under appropπate conditions for a competitive inhibition assay gluS can be labeled, such as by radioactivity or a coloπmetπc compound, such that the number of gluS molecules bound to a binding molecule or converted to product can be determined accurately to assess the effectiveness of the potential antagonist 11 Potential antagonists include small organic molecules, peptides. polypeptides and antibodies that bind to a polynucleotide or poiypeptide of the invention and thereby inhibit or extinguish its activity Potential antagonists also may be small organic molecules, a peptide. a poiypeptide such as a closely related protein or antibody that binds the same sues on a binding molecule, such as a binding molecule, without inducing gluS-induced activities, thereby preventing the action of gluS by excluding gluS from binding Potential antagonists include a small molecule that binds to and occupies the binding site of the poiypeptide thereby preventing binding to cellular binding molecules, such that normal biological activity is prevented Examples of small molecules include but are not limited to small organic molecules, peptides or peptide-like molecules Other potential antagonists include antisense molecules (see Okano, J Neurochem 56 560 ( 1991), OLIGODEOXYNUCLEOTIDES AS ANTISENSE INHIBITORS OF GENE EXPRESSION. CRC Press, Boca Raton, FL (1988). for a descπption of these molecules) Preferred potential antagonists include compounds related to and vaπants ot gluS Each of the DNA sequences provided herein mav be used in the discovery and development of antibacteπal compounds The encoded protein, upon expression, can be used as a target for the screening of antibacteπal drugs Additionally, the DNA sequences encoding the amino terminal regions of the encoded protein or Shine-Delgarno or other translation facilitating sequences of the respective mRNA can be used to construct antisense sequences to control the expression of the coding sequence of interest The invention also provides the use of the poiypeptide, polynucleotide or inhibitor of the invention to interfere with the initial physical interaction between a pathogen and mammalian host responsible for sequelae of infection In particular the molecules of the invention may be used in the prevention of adhesion of bacteria, in particular gram positive bacteria, to mammalian extracellular matrix proteins on in-dwelling devices or to extracellular matrix proteins in wounds, to block gluS protein-mediated mammalian cell invasion by, for example, initiating phosphorylation of mammalian tyrosine kinases (Rosenshine et al , Infect Immun 60 221 1 ( 1992) to block bacteπal adhesion between mammalian extracellular matrix proteins and bacteπal gluS proteins that mediate tissue damage and. to block the normal progression of pathogenesis in infections initiated other than by the implantation of in-dwelling devices or by other surgical techniques The antagonists and agonists of the invention mav be employed, for instance, to inhibit and treat otitis media, conjunctivitis, pneumonia bacteremia meningitis, sinusitis, pleural empyema and endocarditis, and most particularly meningitis, such as for example infection of cerebrospinal fluid Vaccines Another aspect of the invention relates to a method for inducing an immunological response in an individual, particularly a mammal which comprises inoculating the individual with gluS. or a fragment or variant thereof, adequate to produce antibodv and/ or T cell immune response to protect said individual from infection, particularly bacteπal infection and most particularly Streptococcus pneumoniae infection Also provided are methods whereby such immunological response slows bacteπal replication Yet another aspect of the invention relates to a method of inducing immunological response in an individual which compπses dehveπng to such individual a nucleic acid vector to direct expression of gluS, or a fragment or a variant thereof, for expressing gluS. or a fragment or a variant thereof in \ n o in order to induce an immunological response, such as to produce antibodv and or T cell immune response including for example, cvtokine-producing T cells or cvtotoxic T cells, to protect said individual from disease whether that disease is already established within the individual or not One way of administering the gene is by accelerating it into the desired cells as a coating on particles or otherwise Such nucleic acid vector may compnse DNA, RNA. a modified nucleic acid, or a DNA/RNA hvbπd A further aspect of the inv ention relates to an immunological composition which, when introduced into an individual capable or having induced within it an immunological response induces an immunological response in such individual to a gluS or protein coded therefrom wherein the composition comprises a recombinant gluS or protein coded therefrom comprising DNA which codes for and expresses an antigen of said gluS or protein coded therefrom The immunological response may be used therapeutically or prophvlactically and may take the form of antibody immunity or cellular immunity such as that aπsing from CTL or CD4+ T cells A gluS poiypeptide or a fragment thereot mav be fused with co-protein which may not bv itself produce antibodies, but is capable of stabilizing the first protein and producing a fused protein which will hav e immunogenic and protectiv e properties Thus fused recombinant protein preferabK further comprises an antigenic co-protein such as poprotein D from Hemophilus mfluenzae. Glutathione-S-transferase (GST) or beta- galactosidase relativ elv large co-protems which solubihze the protein and facilitate production and punfication thereof Moreover, the co-protein mav act as an adjuvant in the sense of providing a generalized stimulation of the immune system The co-protein may be attached to either the amino or carboxy terminus of the first protein Provided by this invention are compositions, particularly vaccine compositions, and methods compπsing the polypeptides or polynucleotides of the invention and immunostimulatory DNA sequences, such as those descπbed in Sato, Y et al Science 273 352 (1996) Also, provided by this invention are methods using the descπbed polynucleotide or particular fragments thereof which have been shown to encode non-variable regions of bacteπal cell surface proteins in DNA constructs used in such genetic immunization experiments in animal models of infection with Streptococcus pneumoniae will be particularly useful for identifying protein epitopes able to provoke a prophylactic or therapeutic immune response It is believed that this approach will allow for the subsequent preparation of monoclonal antibodies of particular value from the requisite organ of the animal successfully resisting or clearing infection for the development of prophylactic agents or therapeutic treatments of bacteπal infection, particularly Streptococcus pneumoniae infection, in mammals, particularly humans The poiypeptide may be used as an antigen for vaccination of a host to produce specific antibodies which protect against invasion of bacteπa, for example by blocking adherence of bacteria to damaged tissue Examples of tissue damage include wounds in skin or connective tissue caused, e g., by mechanical, chemical or thermal damage or by implantation of indwelling devices, or wounds in the mucous membranes, such as the mouth, mammary glands, urethra or vagina The invention also includes a vaccine formulation which comprises an immunogenic recombinant protein of the invention together with a suitable carrier Since the protein may be broken down in the stomach, it is preferably administered parenterally, including, for example, administration that is subcutaneous, intramuscular, intravenous, or intradermal Formulations suitable for parenteral administration include aqueous and non- aqueous sterile injection solutions which may contain anti-oxidants, buffers, bacteπostats and solutes w hich render the formulation lnsotomc with the bodily fluid, preferably the blood, of the individual, and aqueous and non-aqueous sterile suspensions which may include suspending agents or thickening agents The formulations may be presented in unit-dose or multi-dose containers, for example, sealed ampules and v ials and may be stored in a treeze-dπed condition requiπng only the addition of the sterile liquid earner immediatelv pπor to use The vaccine formulation may also include adjuvant systems tor enhancing the immunogenicity of the formulation, such as oil-in water systems and other systems known in the art The dosage will depend on the specific activity of the vaccine and can be readily determined by routine expeπmentation While the invention has been descπbed with reference to certain gluS protein, it is to be understood that this covers fragments of the naturally occurπng protein and similar proteins with additions, deletions or substitutions which do not substantially affect the immunogenic properties of the recombinant protein Compositions, kits and administration The invention also relates to compositions compπsing the polynucleotide or the polypeptides discussed above or their agonists or antagonists The polypeptides of the invention may be employed in combination with a non-steπle or steπle earner or earners for use with cells, tissues or organisms, such as a pharmaceutical earner suitable for administration to a subject Such compositions compnse, for instance, a media additive or a therapeuticallv effective amount of a poiypeptide of the invention and a pharmaceutically acceptable earner or excipient Such earners may include, but are not limited to, saline, buffered saline, dextrose, water, glycerol, ethanol and combinations thereof The formulation should suit the mode of administration The invention further relates to diagnostic and pharmaceutical packs and kits compπsing one or more containers filled with one or more of the ingredients of the aforementioned compositions of the invention Polypeptides and other compounds of the invention may be employed alone or in conjunction with other compounds, such as therapeutic compounds The pnarmaceutical compositions may be administered in anv effective, convenient manner including, for instance, administration bv topical, oral, anal, vaginal, intravenous liitrapeπtoneal. intramuscular, subcutaneous, intranasal or intradermal routes among others In therapy or as a prophylactic, the active agent may be administered to an individual as an injectable composition, for example as a sterile aqueous dispersion, preferably isotonic Alternatively the composition may be formulated for topical application for example in the form of ointments, creams, lotions, eye ointments, eye drops, ear drops, mouthwash. impregnated dressings and sutures and aerosols, and may contain appropriate conventional additives, including, for example, preservatives, solvents to assist drug penetration, and emollients in ointments and creams Such topical formulations may also contain compatible conventional carriers, for example cream or ointment bases, and ethanol or oleyl alcohol for lotions Such carriers may constitute from about 1 c to about 987c by weight of the formulation, more usually thev will constitute up to about 80% by weight of the formulation For administration to mammals, and particularly humans, it is expected that the daily dosage level of the active agent will be from 0 01 mg/kg to 10 mg/kg, typically around 1 mg kg The physician in any event will determine the actual dosage which will be most suitable for an individual and will ary with the age, weight and response of the particular individual The above dosages are exemplary of the average case There can. of course, be individual instances where higher or lower dosage ranges are meπted, and such are within the scope of this invention In-dwelling devices include surgical implants, prosthetic devices and catheters, i.e , devices that are introduced to the body of an individual and remain in position for an extended time Such devices include, for example, artificial joints, heart valves, pacemakers, v ascular grafts, vascular catheters, cerebrospinal fluid shunts, urinary catheters, continuous ambulatory pentoneal dialysis (CARD) catheters The composition of the invention may be administered by injection to achieve a systemic effect against relevant bacteπa shortly before insertion of an in-dwelling device Treatment may be continued after surgery during the m-body time of the device In addition, the composition could also be used to broaden peπoperative cover for any surgical technique to prevent bacterial wound infections, especially Streptococcus pneumoniae wound infections Many orthopaedic surgeons consider that humans with prosthetic loints should be considered for antibiotic prophylaxis before dental treatment that could produce a bacteremia Late deep infection is a serious complication sometimes leading to loss ot the prosthetic joint and is accompanied by significant morbidity and mortality It may therefore be possible to extend the use of the active agent as a replacement for prophylactic antibiotics in this situation In addition to the therapy described above, the compositions of this invention may be used generally as a wound treatment agent to prevent adhesion of bacteria to matπx proteins exposed in wound tissue and for prophylactic use in dental treatment as an alternative to. or in conjunction with, antibiotic prophylaxis Alternatively, the composition of the invention may be used to bathe an indwelling device immediately before insertion The active agent will preferably be present at a concentration of l μg/ml to lOmg/ml for bathing of wounds or indwelling devices A vaccine composition is conveniently in injectable form Conventional adjuvants may be employed to enhance the immune response A suitable unit dose for vaccination is 0.5-5 microgram/kg of antigen, and such dose is preferably administered 1 -3 times and with an interval of 1-3 weeks. With the indicated dose range, no adverse toxicological effects will be observed with the compounds of the invention which would preclude their administration to suitable individuals Each reference disclosed herein is incorporated by reference herein in its entirety Any patent application to which this application claims pnonty is also incorporated by reference herein in its entirety. EXAMPLES The examples below are carried out using standard techniques, which are well known and routine to those of skill in the art. except where otherwise descπbed in detail The examples are illustrative, but do not limit the invention Example 1 Strain selection. Library Production and Sequencing The polynucleotide having the DNA sequence given in SEQ ID NO 1 was obtained from a library of clones of chromosomal DNA of Streptococcus pneumoniae in E. coll The sequencing data from two or more clones containing overlapping Streptococcus pneumoniae DNAs was used to construct the contiguous DNA sequence in SEQ ID NO 1. Libraπes may be prepared by routine methods, for example Methods 1 and 2 below Total cellular DNA is isolated from Streptococcus pneumoniae 0100993 according to standard procedures and size-fractionated by either of two methods Method 1 Total cellular DNA is mechanically sheared by passage through a needle in order to size-fractionate according to standard procedures. DNA fragments of up to 1 lkbp in size are rendered blunt by treatment with exonuclease and DNA polymerase, and EcoRI linkers added. Fragments are gated into the vector Lambda ZapII that has been cut with EcoRI, the library packaged by standard procedures and E.coh infected with the packaged library The library is amplified by standard procedures. Method 2 Total cellular DNA is partially hydrolyzed with a one or a combination of restπction enzymes appropriate to generate a series of fragments for cloning into library vectors (e g , Rsal, Pall, Alul, Bshl235I), and such fragments are size-fractionated according to standard procedures. EcoRI linkers are hgated to the DNA and the fragments then hgated into the vector Lambda ZapII that have been cut with EcoRI, the library packaged by standard procedures, and E.coli infected with the packaged library The library is amplified by standard procedures. Example 2 gluS Characterization The enzyme mediated incorporation of radiolabelled ammo acid into tRNA may be measured by the aminoacylation method which measures amino acid-tRNA as trichloroacetic acid-precipitable radioactivity from radiolabelled amino acid in the presence of tRNA and ATP (Hughes J. Mellows G and Soughton S. 1980, FEBS Letters, 122.322- 324). Thus inhibitors of glutamyl tRNA synthetase can be detected by a reduction in the trichloroacetic acid precipitable radioactivity relative to the control Alternatively the tRNA synthetase catalysed partial PPi/ATP exchange reaction which measures the formation of radiolabelled ATP from PPi can be used to detect glutamyl tRNA synthetase inhibitors (Calender R & Berg P, 1966, Biochemistr , 5, 1681 - 1690) SEQUENCE LISTING (1) GENERAL INFORMATION (i) APPLICANT: Ja ors i , Deborah La lor, Elizabeth Wang, Min (ii) TITLE OF THE INVENTION: NOVEL STREPTOCOCCAL ERS (iii) NUMBER OF SEQUENCES: 2 (iv) CORRESPONDENCE ADDRESS: (A) ADDRESSEE: SmithKline Beecham Corporation (3) STREET: 709 Swedeiand Road (C) CITY: King of Prussia ( D ) STATE : PA (E) COUNTRY: USA (F) ZIP: 19406-0939 (v) COMPUTER READABLE FORM: (A) MEDIUM TYPE: Diskette (B) COMPUTER: IBM Compatible (C) OPERATING SYSTEM: DOS (D) SOFTWARE: FastΞEQ for Windows Version 2.0 (vi) CURRENT APPLICATION DATA: (A) APPLICATION NUMBER: (B) FILING DATE: 31-OCT-1997 (C) CLASSIFICATION: (vii) PRIOR APPLICATION DATA: (A) APPLICATION NUMBER: 08/844,153 (B) FILING DATE: 18-APR-1997 (A) APPLICATION NUMBER: 9607992.6 (3) FILING DATE: 18-APR-1996 (viii) ATTORNEY/AGENT INFORMATION: (A) NAME: Gimmi , Edward R (3) REGISTRATION NUMBER: 38,891 (C) REFERENCE/DOCKET NUMBER : P31459-1 ( ix ) TELECOMMUNICATION INFORMATION : (A) TELEPHONE: 610-270-4478 (B) TELEFAX: 610-270-5090 ( C ) TELEX : (2) INFORMATION FOR SEQ ID NO : 1 : (l) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1443 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS : single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: Genomic DNA (XI) SEQUENCE DESCRIPTION: SEQ ID NO : 1 : GTACGTTACG CACCAAGTCC AACAGGACTA CTACACATCG GAAATGCCCG TACAGCATTG 60 TTTAACTACT TGTATGCGCG CCATCATGGT GGAACATTTC TCATCCGTAT CGAAGATACT 120 GACCGTAAAC GCCATGTCGA GGATGGTGAA CGTTCACAAC TTGAAAACCT TCGCTGGTTA 180 GGCATGGATT GGGATGAAAG TCCAGAATCA CATGAGAATT ATCGCCAGTC TGAGCGTTTG 240 GACTTGTATC AAAAATACAT TGACCAACTA TTAGCTGAAG GAAAAGCCTA TAAATCTTAC 300 GTTACAGAAG AAGAGTTGGC AGCTGAACGT GAACGTCAAG AAGCTGCTGG TGAAACACCT 360 CGATATATCA ACGAATACCT TGGTATGAGT GAAGAGGAAA AAGCGGCTTA TATCGCAGAA 420 CGTGAAGCAG CTGGTATCAT ACCAACAGTT CGTTTGGCTG TCAATGAGTC AGGTATCTAC 480 AAGTGGCATG ATATGGTCAA AGGTGATATC GAATTTGAAG GTGGCAATAT CGGCGGTGAC 540 TGGGTTATCC AAAAGAAAGA CGGTTACCCA ACTTACAACT TTGCCGTTGT TATCGATGAC 500 CACGATATGC AAATCTCTCA TGTTATCCGT GGAGATGACC ATATTGCTAA TACACCAAAA 660 CAGCTTATGG TCTATGAAGC TCTTGGTTGG GAAGCTCCAG AGTTTGGTCA CATGACCTTG "C ATTATCAACT CTGAGACTGG TAAGAAGTTA TCTAAACGTG ATACTAATAC ACTTCAATTT " 30 ATCGAAGATT ACCGAAAGAA AGGTTACCTT CCAGAAGCAG TCTTTAACTT TATTGCTCTT 340 CTTGGTTGGA ACCCAGGTGG TGAAGATGAG ATTTTCTCTC GTGAAGAACT CATTAAACTT 900 TTTGATGAAA ACCGCCTCAG CAAGTCACCA GCAGCCTTTG ATCAGAAAAA ACTAGACTGG 960 ATGAGCAATG ATTATATCAA GAATGCAGAC CTTGAAACCA TCTTTGAAAT GGCAAAACCA 1020 TTCTTAGAGG AAGCAGGCCG TTTGACTGAC AAGGCTGAAA AATTATTCGA TCTCTATAAA 080 CCACAAATGA AATCAGTAGA TGAGATTATC CCATTGACAG ATCTTTTCTT CTCAGATTTC 1140 CCAGAATTGA CAGAAGCAGA GCGCGAAGTC ATGACGGGTG AAACAGTTCC AACAGTTCTT 1200 GAAGCATTCA AAGCAAAACT TGAAGCGATG ACAGATGATG AATTTGTGAC AGAAAATATC 1260 TTCCCGCAAA TTAAAGCAGT CCAAAAAGAA ACAGGTATTA AAGGGAAAAA TCTTTTCATG 1320 CCTATTCGTA TCGCAGTTTC AGGCGAAATG CATGGGCCAG AATTACCAGA TACAATTTTC 1380 TTGCTTGGAC GTGAAAAATC AATTCAGCAT ATCGAAAACA TTCTAAAAGA AATCTCTAAA 1 40 TAA 1443 (2) INFORMATION FOR SEQ ID NO : 2 : (I) SEQUENCE CHARACTERISTICS: (A) LENGTH: 480 ammo acids (B) TYPE: amino acid (C) STRANDEDNESΞ : single (D) TOPOLOGY: linear (II) MOLECULE TYPE: protein (XI) SEQUENCE DESCRIPTION: SEQ ID NO : 2 : Val Arg Tyr Ala Pro Ser Pro Thr Gly Leu Leu His lie Gly Asn Ala 1 5 10 15 Arg Thr Ala Leu Phe Asn Tyr Leu Tyr Ala Arg His His Gly Gly Thr 20 25 30 Phe Leu lie Arg lie Glu Asp Tr.r Asp Arg Lys Arg His Val Glu Asp 35 40 45 Gly Glu Arg Ser Gin Leu Glu Asn Leu Arg Trp Leu Gly Met Asp Trp 50 55 60 Asp Glu Ser Pro Glu Ser His Glu Asn Tyr Arg Gin Ser Gl.. Arg Leu 65 70 75 80 Asp Leu Tyr Gin Lys Tyr lie Asp Gin Leu Leu Ala Glu Gly Lys Ala 85 90 95 Tyr Lys Ser Tyr Val Thr Glu Glu Glu Leu Ala Ala Glu Arg Glu Arg 100 105 110 Gin Glu Ala Ala Gly Glu Thr Pro Arg Tyr He Asn Glu Tyr Leu Gly 115 120 125 Met Ser Glu Gl Glu Lys Ala Ala Tyr He A-a Glu Arg Gl-_ Ala Ala 130 135 140 Gly He He Pro Thr Val Arg Leu Ala Val Asn Glu Ser Gly He Tyr 145 150 155 160 Lys Trp His Asp Met Val Lys Gly Asp He Glu Phe Glu Gly Gly Asn 165 170 175 He Gly Gly Asp Trp Val He Gin Lys Lys Asp Gly Tyr Pro Thr Tyr 180 185 190 Asn Phe Ala Val Val He Asp Asp His Asp Met Gin He Ser H s Val 195 200 205 He Arg Gly Asp Asp His He Ala Asn Thr Pro Lys Gin Leu Met Val 210 215 220 Tyr Glu Ala Leu Gly Trp Glu Ala Pro Glu Pne Gly His Met Thr Leu 225 230 235 240 He He Asn Ser Glu Thr Gly Lys Lys Leu Ser Lys Arg Asp Thr Asn 245 250 255 Thr Leu Gin Pne He Glu Asp Tyr Arg Lys Lys Gly Tyr Leu Pro Glu 260 265 270 Ala Val Phe Asn Phe He Ala Leu Leu Gly Trp Asn Pro Gly Gly Glu 275 280 285 Asp Glu He Phe Ser Arg Glu Glu Leu He Lys Leu Phe Asp Glu Asn 290 295 300 Arg Leu Ser Lys Ser Pro Ala Ala Phe Asp Gin Lys Lys Leu Asp Trp 305 310 315 320 Met Ser Asn Asp Tyr He Lys Asn Ala Asp Leu Glu Thr He Phe Glu 325 330 335 Met Ala Lys Pro Phe Leu Glu Glu Ala Gly Arg Leu Thr Asp Lys Ala 340 345 350 Glu Lys Leu Phe Asp Leu Tyr Lys Pro Gin Met Lys Ser Val Asp Glu 355 360 365 He He Pro Leu Thr Asp Leu Phe Phe Ser Asp Phe Pro Glu Leu Thr 370 375 380 Glu Ala Glu Arg Glu Val Met Thr Gly Glu Thr Val Pro Thr Val Leu 385 390 395 400 Glu Ala Phe Lys Ala Lys Leu Glu Ala Met Thr Asp Asp Glu Phe Val 405 410 415 Thr Glu Asn He Phe Pro Gin He Lys Ala Val Gin Lys Glu Thr Gly 420 425 430 He Lys Gly Lys Asn Leu Phe Met Pro He Arg He Ala Val Ser Gly 435 440 445 Glu Met His Gly Pro Glu Leu Pro Asp Thr He Phe Leu Leu Gly Arg 450 455 460 Glu Lys Ser He Gin His He Glu Asn He Leu Lys Glu He Ser Lys 465 470 475 480

Claims: What is claimed is: 1 An isolated polynucleotide compπsing a polynucleotide sequence selected from the group consisting of (a) a polynucleotide hav g at least a 70% identity to a polynucleotide encoding a poiypeptide compnsing the am o acid sequence of SEQ ID NO 2, (b) a polynucleotide which is complementary to the polynucleotide of (a), (c) a polynucleotide havmg at least a 70% identity to a polynucleotide encoding the same mamre poiypeptide expressed by the gluS gene contained in the Streptococcus pneumoniae of the deposited strain, and (d) a polynucleotide compπsing at least 15 sequential bases of the polynucleotide of (a), (b) or (c) 2 The polynucleotide of Claim 1 wherem the polynucleotide is DNA 3 The polynucleotide of Claim 1 wherein the polynucleotide is RNA 4 The polynucleotide of Claim 2 compπsing the nucleic acid sequence set forth in SEQ ID NO 1 5 The polynucleotide of Claim 2 compπsing nucleotide set fonh in SEQ ID NO 1 6 The polynucleotide of Claim 2 which encodes a poiypeptide compπsing the amino acid sequence of SEQ ID NO 2 7 A vector compπsing the polynucleotide of Claim 1 8 A host cell compπsing the vector of Claim 7 9 A process for producing a poiypeptide compπsing expressing from the host cell of Claim 8 a poiypeptide encoded by said DNA 10 A process for producing a gluS poiypeptide or fragment comprising cultuπng a host of claim 8 under conditions sufficient for the production of said poiypeptide or fragment 1 1 A poiypeptide compnsing an ammo acid sequence which is at least 70% identical to the amino acid sequence of SEQ ID NO 2 12 A poiypeptide compπsing an amino acid sequence as set forth in SEQ ID NO 2 13 An antibody against the poiypeptide of claim 1 1 14 .An antagonist which inhibits the activitv or expression of the poiypeptide of claim 1 1 15 A method for the treatment of an individual in need of gluS poiypeptide compnsing: administering to the individual a therapeutically effective amount of the poiypeptide of claim 11 16. A method for the treatment of an individual having need to inhibit gluS poiypeptide compnsmg. adm isteπng to the individual a therapeutically effective amount of the antagonist of Claim 14 17 A process for diagnosing a disease related to expression or activity of the poiypeptide of claim 1 1 m an individual compnsmg (a) determining a nucleic acid sequence encoding said poiypeptide, and/or (b) analyzing for the presence or amount of said poiypeptide in a sample denved from the individual. 18 A method for identifying compounds which interact with and inhibit or activate an activity of the poiypeptide of claim 1 1 compnsmg contacting a composition compπsing the poiypeptide with the compound to be screened under conditions to permit interaction between the compound and the poiypeptide to assess the interaction of a compound, such interaction being associated with a second component capable of providing a detectable signal in response to the interaction of the poiypeptide with the compound; and determining whether the compound interacts with and activates or inhibits an activity of the polypetide by detecting the presence or absence of a signal generated from the interaction of the compound with the poiypeptide 19 A method for inducing an immunological response in a mammal which compπses inoculating the mammal with gluS poiypeptide of claim 1 1, or a fragment or vaπant thereof, adequate to produce antibody and/or T cell immune response to protect said animal from disease. 20. A method of inducing immunological response in a mammal which compπses delivering a nucleic acid vector to direct expression of gluS poiypeptide of claim 11, or fragment or a vaπant thereof, for expressing said gluS poiypeptide. or a fragment or a variant thereof in vivo in order to induce an immunological response to produce antibody and/ or T cell immune response to protect said animal from disease

Inventors: JAWORSKI DEBORAH D, LAWLOR ELIZABETH J, WANG MIN, JAWORSKI, DEBORAH, D., LAWLOR, ELIZABETH, J., WANG, MIN
Applicants: JAWORSKI DEBORAH D, LAWLOR ELIZABETH J, SMITHKLINE BEECHAM CORP, WANG MIN, JAWORSKI, DEBORAH, D., LAWLOR, ELIZABETH, J., SMITHKLINE BEECHAM CORPORATION, WANG, MIN
Application year: 1997
Main classification: C12N15
IPC codes: A61K38, A61K39, A61K45, A61P31, C07K16, C12N1, C12N5, C12N9, C12N15, C12Q1, C12R1