CN1357045A - 外表面蛋白质及其基因和用途 - Google Patents
外表面蛋白质及其基因和用途 Download PDFInfo
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- CN1357045A CN1357045A CN99814781A CN99814781A CN1357045A CN 1357045 A CN1357045 A CN 1357045A CN 99814781 A CN99814781 A CN 99814781A CN 99814781 A CN99814781 A CN 99814781A CN 1357045 A CN1357045 A CN 1357045A
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Abstract
根据本发明,在B组链球菌中鉴定了一系列基因,其产物可能位于生物体的外表面上。该基因或其功能性片段可用于治疗物质,例如使患者免受微生物感染的疫苗的制备。
Description
发明领域
该项发明是关于外表面蛋白质的鉴定及其基因和用途，尤其是涉及在免疫治疗和药物筛选上的应用。
发明背景
B组链球菌(GBS)也被称为无乳链球菌，是各种病的病原体。特别是，GBS可引起：
早期发作新生期感染
该感染通常开始于子宫，导致新生儿严重的败血病和肺炎，如果不能及时治疗将其致死，即使得到治疗也会有10-20％的死亡率。
晚期发作新生期感染
该感染多发于婴儿刚出生至大约3个月期间，可致败血病，90％的病例伴发脑膜炎。其它病灶性感染包括脑膜炎、脓毒性关节炎、脓肿和眼内炎。
成人感染
该感染似乎越来越常见且最频繁地发生于刚生育过婴儿的、年长的、无免疫应答的女性身上。其特征为败血病和病灶性感染，包括脑膜炎、脓毒性关节炎、脓肿和眼内炎。
尿道感染
GBS是尿道感染的成因，在妊娠期的所有感染中约占10％。
家畜感染
GBS引起奶牛的慢性乳腺炎。导致产奶量下降，因此具有值得注意的经济重要性。
虽然GBS感染可用抗生素治疗，但免疫学的方法是优选的。因此人们希望找到一种能被用于有治疗效果的疫苗中的免疫原。
发明概要
本发明基于在GBS中的一系列基因的鉴定，以及相关的生物体，该生物体的产物可能与其外表面相关联且因此可被用作免疫治疗的靶。
根据本发明的一个方面，肽由包括任意的已被鉴定为MS4、MS10、MS11、MS14和MS16的可得自GBS的基因，或其同源物或功能性片段的操纵子所编码。此种肽适合用于治疗，例如当被分离后。
此处所用的术语“功能性片段”是指一部分保留整个基因或肽活性的基因或肽。例如肽的功能性片段可用做抗原决定因子，在疫苗或抗体生产方面颇有用处。
基因片段可用于编码活性肽。另外，该基因片段在基因疗法、体内野生型基因定位来发挥治疗作用方面有实用。
本发明的肽可包含确定的任一氨基酸序列，如SEQ ID NOS.2、4、6、8、10和12，或包含上述序列的功能性片段。
因为位于细胞外或细胞表面的位置，本发明的肽可为生产抗GBS治疗上有效的疫苗的候选物。“治疗上有效的”是指包括疫苗的预防作用。例如，疫苗可包含本发明所述的肽或用于其表达的工具以治疗感染。
这种疫苗可在妇女怀孕前或怀孕期间给药来保护母亲和新生儿免受GBS感染。
根据本发明的另一方面，此肽或基因可用于筛选潜在的抗微生物药物或毒性检测。
本发明的另一个方面是在此处鉴定的任意产物的用途，用于与GBS菌株感染相关病症的治疗或预防。
虽然已经描述了此蛋白质用于病人的治疗，但该产物的兽医用途也被视为在本发明的范围之内。尤其是，该肽或疫苗可被用于慢性乳腺炎的治疗，特别是对奶牛的治疗。
发明描述
本发明与B组链球菌菌株M732有关，然而所有的GBS菌株和许多其它的细菌菌株都可能包含相关的肽或蛋白质，它们都有与M732的肽同源的氨基酸序列。可能含有此肽的生物体，包括但不仅限于此：肺炎链球菌，酿脓链球菌，猪链球菌，米氏链球菌，C组和G组链球菌，还有肠球菌。按照描述GBS的相同方法，可以开发出这些菌株中的相应疫苗。
优选地，用于生产疫苗的肽与在此鉴定的肽有超过40％的序列相似性，优选可以超过60％，最优选可多于80％的序列相似性，例如95％相似性。
在鉴定出本发明的一个基因后，可以用此基因序列在别的微生物中确定同源性。以此方式还可以确定别的微生物是否有相似的外表面产物。通过在现存的数据库例如：EMBL或Genbank中搜索，可以确定序列的同源性。
本发明的肽或蛋白质可通过本领域已知的方法被纯化和分离。特别是，确定基因序列后，可以用重组技术在合适的宿主中表达基因。活性片段和同源物可以被鉴定出来，并在治疗领域中应用。例如，肽或其活性片段可在疫苗中作为抗原决定簇，来引起免疫答应。其也可以被用于抗体的制备，用于被动免疫或诊断应用。合适的抗体包括单克隆抗体或其片段，包括单链fv片段。制备抗体的方法对本领域的技术人员来说是显而易见的。
基于减毒微生物的疫苗的制备是本领域技术人员已知的。如需要或希望的话，疫苗组合物可与合适的载体或佐剂如明矾一起配制，并用于治疗，来提供抗B组链球菌或其它相关微生物的有效免疫作用。疫苗配剂的制备对本领域的技术人员来说是显而易见的。
通常，本发明用于治疗的活性成分的合适的量以及合适载体或赋形剂以及给药途径的选择对本领域的技术人员来说是公知的。这些因素可根据已知标准选择或确定，诸如所治疗病症的性质/严重性、受治疗者的类型或健康状况等。
本发明的产品可按如下方法鉴定：
将GBS接种于Todd-Hewitt氏链球菌肉汤培养基中，允许在37℃下培养过夜。细胞被离心收集和用磷酸盐缓冲盐水(PBS)洗涤。将细胞重新悬浮在渗透性缓冲液(20％(W/V)蔗糖，20Mm Tris-HCl pH7.0，10mM MgCl2)中，该渗透性缓冲液含有蛋白酶抑制剂(1mM PMSF，10μM碘乙酸，10mM1，10-二氮杂菲，1μM胃酶抑素A)和终浓度为4单位/微升变溶菌素，在37℃培养(振荡)2小时。
先用高速离心机除去细胞和碎屑，再用超高速离心1小时。所得到的含有细胞壁蛋白质的上清液用超滤设备加压浓缩(分子量截断值为10,000)。
样品对超高水透析后冻干。经过在填充缓冲液中再悬浮，用制备性两向凝胶电泳分离出蛋白质。电泳后，选一个单独的点用于研究。对该点进行凝胶内胰蛋白酶消化。从胶状中提取产生的肽，用微内径RP-HPLC纯化。每隔45秒收集一次级分，与紫外吸收区相应的部分用延时提取-基体辅助激光解吸-飞行时间质谱、(DE-MALDI-TOF-MS)分析。然后用Nanospray-MS/MS对在空白制剂中未观察到的肽进行测序。
使用此肽序列的信息，设计了简并低聚核苷酸，将其用于聚合酶链反应(PCR)来扩增位于所鉴定的肽序列之间的DNA片段。
PCR扩增反应的结果是产生几个多聚核苷酸片段，其中每一片段按照制造商的说明书被克隆到pCR 2.1-TOPO载体(Invitrogen BV，荷兰)中。
每一质粒中的DNA片段通过测序被鉴定，然后如下所述被用于获得全长基因序列。
用已鉴定的DNA片段，低聚核苷酸引物被设计用于基因组DNA测序。这些引物被设计以便从得到的序列“向外的”方向排序。一旦阅读，即可检查获得的序列是否已经到达基因的5’端和3’端。通过检查同源序列鉴定了这些特征的存在，对于5’末端来说，在Shine-Dalgarno共有序列之前存在AUG起始密码子(或公认的替换物)而对于3’末端来说，存在翻译终止密码子。
根据全长基因的鉴定，引物被设计用于从GBS基因组DNA扩增全长产物。所用的引物包括限制酶识别位点(在5’末端的NcoI和在3’末端的Eco0109I)，允许产物随后克隆到所用的乳球菌表达体系中。
用引物进行PCR反应，并把产物克隆到pCR 2.1克隆载体(Invitrogen)中。在确认克隆片段存在后，用限制酶NcoI和Eco0109I切除该DNA。
插入此片段的载体是pNZ8048的修饰变体(Kuipers，O.P.等人(1998)J.Biotech 64：15-21)。这种含有乳球菌复制起点、氯霉素抗性标记、可诱导的乳链菌肽启动子和多克隆位点的载体通过用2个10X组氨酸标记取代位点得以改变多克隆，侧接于带有NcoI位点的5’末端，在含有多克隆位点(包括Eco0109I位点)和His标记的3’末端的终止密码子的中间分开。
插入目的基因，这样一个10X组氨酸标记处在相对于密码区的3’位置。把重组质粒转化到乳酸乳球菌(L.lactis)(菌株NZ9000-Kuipers，O.p.等人(1998)见上文)中，形成一种400ml的液体培养物，通过将乳链菌肽加到培养物中来诱导蛋白质的翻译。培养2小时后，收获细胞并用玻珠搅打溶胞，将生成的溶胞产物离心分离，然后通过金属亲合性(Talon，clonetech)柱。在用咪唑洗脱结合的蛋白质前反复洗柱。
为了鉴定含有组氨酸标记的重组蛋白质的级分，每个级分的等分试样都用SDS-PAGE、蛋白质印迹法分析，并用抗-His抗体探测。
然后用得到的重组蛋白质免疫新西兰白兔，在免疫前收集免疫前血清。在加强免疫之后，处死白兔，收集血清，用于蛋白质印迹法、ELISA和动物保护模型。
使用获自动物研究的血清，进行免疫吸附研究。
B组链球菌在20ml Todd-Hewitt氏链球菌肉汤(THB)中培养8小时，收集后再悬浮于5ml PBS中。在96孔平板(Nunc免疫-吸附)中，用50μl等分试样覆盖加样孔，在4℃放置过夜以吸收细菌到平板上。用GBS洗平板两次，然后在37℃下用加入3％BAS的PBS封闭1小时。再次洗涤平板。在PBS中制得连续10倍的血清稀释液且50μl稀释液被加到平板的孔中，一式两份。盖上平板并在37℃培养1小时。洗涤平板，然后在每个孔中加入浓度为1∶5000的50μl抗兔碱性磷酸酶缀合的第二抗体。在37℃培养1小时后，再次洗涤平板。把50μl底物(PNPP)加入每个孔，在405nm处读取吸收度前反应30min。
进行动物保护研究，检验保护作用对免疫接种兔的有效性。
GBS M732在THB中培养，直至对数中期，约需5小时。在计数室中进行细胞计数，在免疫前或试验血清中稀释细菌浓度至2×107/ml。取50μl通过腹膜内途径注射入出生0-1天的小鼠。在48小时内观察小鼠的存活状况。
下面的实施例阐述了本发明。
实施例1
第一个质粒被称为MS4。克隆的DNA片段被测序，核苷酸和推断的氨基酸序列(SEQ ID NO.1和2)被用于检索蛋白质数据库。
可在产气荚膜梭菌、流感嗜血菌、淡黄奈瑟氏球菌和Thermatogamaritima中鉴定GBS MS4基因产物的同源物。在所有的情况下同源物都是鸟氨酸转氨甲酰酶(OCT)的基因。在真核体系中这种酶催化尿素循环的第二步反应-鸟氨酸转化为瓜氨酸，该反应需氨甲酰磷酸。在原核生物中，ODC是与精氨酸脱氨酶活性有关的三种酶之一-保护细菌不受酸侵蚀。尤其，ODC有助于瓜氨酸转为鸟氨酸和氨甲酰磷酸(与真核生物中的相反的作用)(Casiano-colon，A and Marquis，R.E.1998.Ap pl.Environ.Microbiol.54：1318-1324，Cunin，R.等人1986.Microbiol.Rev.50：314-352)。
如上所述进行了动物保护研究。结果如下：处理 幼犬数 在时间点(hrs)存活的幼犬数
24 48PBS 15 6 0免疫前 41 18 1试验 41 33 14
实施例2
第二个质粒被称为MS11。核苷酸和推断的氨基酸序列(SEQ ID NOS.3和4)被用于检索蛋白质数据库。
GBS MS11基因产物的同源物可在德氏乳杆菌，海栖热袍菌，丙酮丁醇梭菌，巨大芽孢杆菌，Triticum aestivium和集胞蓝细菌PCC6803中被鉴定。
在所有的情况下同源物都是磷酸甘油激活酶(PGK)蛋白质的基因。PGK是糖酵解途径中的主要酶，与甘油醛3-磷酸-转变为磷酸烯醇丙酮酸的反应有关。尤其，与甘油酸-1，3-二磷酸与3-磷酸-甘油酸之间反应的催化作用有关，在向前的反应中释放一个磷酸。
实施例3
第三个质粒被称为pMS16。5’和3’末端克隆DNA片段被测序且5’端片段的核苷酸和推断的氨基酸序列被显示于SEQ ID NOS.5和6，3’端片段的核苷酸和推断的氨基酸序列被显示于SEQ ID NOS.7和8。
GBS MS16基因产物的同源物可以在嗜热脂肪芽孢杆菌、枯草芽孢杆菌和生殖道枝原体中被鉴定。
在所有的情况下同源物都是编码葡萄糖-6-磷酸异构酶(GPI)蛋白质的基因。
葡萄糖-6-磷酸异构酶催化糖酵解(G6P到F6P)和糖异生(F6P到G6P)过程中的葡萄糖-6-磷酸和果糖-6-磷酸之间的反应。已证明gpi基因中的突变赋予生物体嘌呤类似物敏感性。
实施例4
第四个质粒被称为pMS14。克隆的DNA片段被测序，核苷酸和推断的氨基酸序列(SEQ ID NO.9和10)被用于检索蛋白质数据库。
GBS MS14基因产物的同源物可在嗜热脂肪芽孢杆菌，Mus musculus，Bos taurus和玉米中被鉴定。在所有的情况下同源物均为嘌呤核苷磷酸酶(PNP)蛋白质的基因。此酶的作用是在正磷酸存在时切割鸟嘌呤核苷或肌苷成为其各自的碱基和糖-1-磷酸分子。
实施例5
第五个质粒被称为pMS10。克隆的DNA片段被测序，核苷酸和推断的氨基酸序列(SEQ ID NO.11和12)被用于检索蛋白质数据库。
GBS MS10基因产物的同源物可在变异链球菌，Nicotiana Plumb，Pisum sati vum和玉米中被鉴定。在所有的情况下同源物都是非磷酸化，NADP-依赖性甘油醛-3-磷酸脱氢酶(NPGAP-3-DH)蛋白质的基因。NPGAP-3-DH已被报道作为在变异链球菌中产生NADPH用于生物合成反应的重要工具(与符合糖酵解途径要求的NAD-特异性GAP-3-DH相反)(Boyd，D.A.，Cvitkovitch，D.G.和Hamilton，I.R 1995细菌学杂志。177：2622-2727)。
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100 105 110aga atg gtt gaa gag ctt gct gaa ttt tct gga gta cct gtc tgg aat 384Arg Met Val Glu Glu Leu Ala Glu Phe Ser Gly Val Pro Val Trp Asn
115 120 125ggt tta aca gat gaa tgg cat cca aca caa atg cta gct gac tac ctt 432Gly Leu Thr Asp Glu Trp His Pro Thr Gln Met Leu Ala Asp Tyr Leu
130 135 140act atc aaa gaa aac ttc ggt aaa ctt gaa ggt att act ctt gtt tac 480Thr Ile Lys Glu Asn Phe Gly Lys Leu Glu Gly Ile Thr Leu Val Tyr145 150 155 160tgt ggt gac gga cgt aac aat gtt gcc aac tcg ctt tta gtg gct ggg 528Cys Gly Asp Gly Arg Asn Asn Val Ala Asn Ser Leu Leu Val Ala Gly
165 170 175act ttg atg ggg gtc aat gta cac atc ttt tct cca aaa gaa ctt tty 576Thr Leu Met Gly Val Asn Val His Ile Phe Ser Pro Lys Glu Leu Phe
180 185 190ccw gct gaa gag att gtt aaa ttg gct gaa gga tat gcc aaa gaa tct 624Xaa Ala Glu Glu Ile Val Lys Leu Ala Glu Gly Tyr Ala Lys Glu Ser
195 200 205ggg gct cac gtt ctc gtt act gat aat gta gac gaa gct gta aag gga 672Gly Ala His Val Leu Val Thr Asp Asn Val Asp Glu Ala Val Lys Gly
210 215 220gca gac gtc ttt tac act gat gtc tgg gta tcg atg gga gaa gaa gat 720Ala Asp Val Phe Tyr Thr Asp Val Trp Val Ser Met Gly Glu Glu Asp225 230 235 240aag ttc aaa gaa cgc gtt gaa ctt ctt caa cca tat caa gta aac atg 768Lys Phe Lys Glu Arg Val Glu Leu Leu Gln Pro Tyr Gln Val Asn Met
245 250 255gaa ctg att aaa aaa gct aat aat gat aat ctt atc ttc tta cac tgc 816Glu Leu Ile Lys Lys Ala Asn Asn Asp Asn Leu Ile Phe Leu His Cys
260 265 270tta cct gca ttc cat gat aca aat acc gtt tat ggc aaa gac gtc gct 864Leu Pro Ala Phe His Asp Thr Asn Thr Val Tyr Gly Lys Asp Val Ala
275 280 285gaa aaa ttt ggg gtc aag gaa atg gaa gtt act gat gaa gtc ttc cgt 912Glu Lys Phe Gly Val Lys Glu Met Glu Val Thr Asp Glu Val Phe Arg
290 295 300agc aaa tat gct cgt cat ttc gac caa gct gaa aat cgt atg cac act 960Ser Lys Tyr Ala Arg His Phe Asp Gln Ala Glu Asn Arg Met His Thr305 310 315 320att aaa gct gta atg gct gca acc ctt gga aat ctt ttc att cca aaa 1008Ile Lys Ala Val Met Ala Ala Thr Leu Gly Asn Leu Phe Ile Pro Lys
325 330 335gtt taa 1014Val<210>2<211>337<212>PRT<213>B组链球菌<400> 2Met Thr Gln Val Phe Gln Gly Arg Ser Phe Leu Ala Glu Lys Asp Phe1 5 10 15Ser Arg Glu Glu Phe Glu Tyr Leu Ile Asp Phe Ser Ala His Leu Lys
20 25 30Asp Leu Lys Lys Arg Gly Val Pro His His Tyr Leu Glu Gly Lys Asn
35 40 45Ile Ala Leu Leu Phe Glu Lys Thr Ser Thr Arg Thr Arg Ala Ala Phe
50 55 60Thr Thr Ala Ala Ile Asp Leu Gly Ala His Pro Glu Tyr Leu Gly Ala65 70 75 80Asn Asp Ile Gln Leu Gly Lys Lys Glu Ser Thr Glu Asp Thr Ala Lys
85 90 95Val Leu Gly Arg Met Phe Asp Gly Ile Glu Phe Arg Gly Phe Ser Gln
100 105 110Arg Met Val Glu Glu Leu Ala Glu Phe Ser Gly Val Pro Val Trp Asn
115 120 125Gly Leu Thr Asp Glu Trp His Pro Thr Gln Met Leu Ala Asp Tyr Leu
130 135 140Thr Ile Lys Glu Asn Phe Gly Lys Leu Glu Gly Ile Thr Leu Val Tyr145 150 155 160Cys Gly Asp Gly Arg Asn Asn Val Ala Asn Ser Leu Leu Val Ala Gly
165 170 175Thr Leu Met Gly Val Asn Val His Ile Phe Ser Pro Lys Glu Leu Phe
180 185 190Xaa Ala Glu Glu Ile Val Lys Leu Ala Glu Gly Tyr Ala Lys Glu Ser
195 200 205Gly Ala His Val Leu Val Thr Asp Asn Val Asp Glu Ala Val Lys Gly
210 215 220Ala Asp Val Phe Tyr Thr Asp Val Trp Val Ser Met Gly Glu Glu Asp225 230 235 240Lys Phe Lys Glu Arg Val Glu Leu Leu Gln Pro Tyr Gln Val Asn Met
245 250 255Glu Leu Ile Lys Lys Ala Asn Asn Asp Asn Leu Ile Phe Leu His Cys
260 265 270Leu Pro Ala Phe His Asp Thr Asn Thr Val Tyr Gly Lys Asp Val Ala
275 280 285Glu Lys Phe Gly Val Lys Glu Met Glu Val Thr Asp Glu Val Phe Arg
290 295 300Ser Lys Tyr Ala Arg His Phe Asp Gln Ala Glu Asn Arg Met His Thr305 310 315 320Ile Lys Ala Val Met Ala Ala Thr Leu Gly Asn Leu Phe Ile Pro Lys
325 330 335Val<210>3<211>1197<212>DNA<213>B组链球菌<220><221>CDS<222>(1)..(1197)<400>3atg gct aaa ttg act gtt aaa gac gtt gat ttg aag gta aaa aaa gtc 48Met Ala Lys Leu Thr Val Lys Asp Val Asp Leu Lys Val Lys Lys Val1 5 10 15ctc gtt cgt gtt gac ttt aat gtg cct ttg aaa gac ggc gtt atc act 96Leu Val Arg Val Asp Phe Asn Val Pro Leu Lys Asp Gly Val Ile Thr
20 25 30aac gac aac cgt atc act gcg gct ctt cca aca atc aag tat atc atc 144Asn Asp Asn Arg Ile Thr Ala Ala Leu Pro Thr Ile Lys Tyr Ile Ile
35 40 45gaa caa ggt ggt cgt gct atc ctc ttc tct cac ctt gga cgt gtt aaa 192Glu Gln Gly Gly Arg Ala Ile Leu Phe Ser His Leu Gly Arg Val Lys
50 55 60gaa gaa gct gac aaa gaa gga aaa tca ctt gca ccg gta gct gct gat 240Glu Glu Ala Asp Lys Glu Gly Lys Ser Leu Ala Pro Val Ala Ala Asp65 70 75 80tta gct gct aaa ctt ggt caa gat gtt gta ttc cca ggt gtt act cgt 288Leu Ala Ala Lys Leu Gly Gln Asp Val Val Phe Pro Gly Val Thr Arg
85 90 95ggt gca aaa tta gaa gaa gca atc aat gct ttg gaa gat gga caa gtt 336Gly Ala Lys Leu Glu Glu Ala Ile Asn Ala Leu Glu Asp Gly Gln Val
100 105 110ctt ttg gtt gaa aac act cgt ttt gaa gat gtt gac ggt aag aaa gaa 384Leu Leu Val Glu Asn Thr Arg Phe Glu Asp Val Asp Gly Lys Lys Glu
115 120 125tct aag aat gac gaa gaa ctt ggt aaa tac tgg gct tca ctt gga gat 432Ser Lys Asn Asp Glu Glu Leu Gly Lys Tyr Trp Ala Ser Leu Gly Asp
130 135 140gga atc ttc gtt aac gat gca ttt ggt aca gca cac cgt gct cat gca 480Gly Ile Phe Val Asn Asp Ala Phe Gly Thr Ala His Arg Ala His Ala145 150 155 160tca aac gta ggt att tca gca aac gtt gaa aaa gct gta gct ggt ttc 528Ser Asn Val Gly Ile Ser Ala Asn Val Glu Lys Ala Val Ala Gly Phe
165 170 175ctt ctt gaa aac gaa att gct tac atc caa gaa gca gtt gaa act cca 576Leu Leu Glu Asn Glu Ile Ala Tyr Ile Gln Glu Ala Val Glu Thr Pro
180 185 190gaa cgc cca ttc gta gct att ctt ggt ggc tca aaa gtt tct gat aag 624Glu Arg Pro Phe Val Ala Ile Leu Gly Gly Ser Lys Val Ser Asp Lys
195 200 205att ggt gtt atc gaa aac ctt ctt gaa aaa gct gat aaa gtt ctt atc 672Ile Gly Val Ile Glu Asn Leu Leu Glu Lys Ala Asp Lys Val Leu Ile
210 215 220ggt ggt ggt atg act tac aca ttc tac aaa gct caa ggt atc gaa atc 720Gly Gly Gly Met Thr Tyr Thr Phe Tyr Lys Ala Gln Gly Ile Glu Ile225 230 235 240ggt aac tca ctt gta gaa gaa gac aaa ttg gat gtt gct aaa gac ctc 768Gly Asn Ser Leu Val Glu Glu Asp Lys Leu Asp Val Ala Lys Asp Leu
245 250 255ctt gaa aaa tca aac ggt aaa ttg atc ttg cca gtt gac tca aaa gaa 816Leu Glu Lys Ser Asn Gly Lys Leu Ile Leu Pro Val Asp Ser Lys Glu
260 265 270gca aac gca ttt gct ggt tat act gaa gtt cgc gac act gaa ggt gaa 864Ala Asn Ala Phe Ala Gly Tyr Thr Glu Val Arg Asp Thr Glu Gly Glu
275 280 285gca gtt tca gaa ggg ttc ctt ggt ctt gac atc ggt cct aaa tca atc 912Ala Val Ser Glu Gly Phe Leu Gly Leu Asp Ile Gly Pro Lys Ser Ile
290 295 300gct aaa ttt gat gaa gca ctt act ggt gct aaa aca gtt gta tgg aac 960Ala Lys Phe Asp Glu Ala Leu Thr Gly Ala Lys Thr Val Val Trp Asn305 310 315 320gga cct atg ggt gtc ttt gaa aac cct gac ttc caa gct ggt aca atc 1008Gly Pro Met Gly Val Phe Glu Asn Pro Asp Phe Gln Ala Gly Thr Ile
325 330 335ggt gta atg gac gct atc gtt aaa caa cca ggc gtt aaa tca atc atc 1056Gly Val Met Asp Ala Ile Val Lys Gln Pro Gly Val Lys Ser Ile Ile
340 345 350ggt ggt ggt gat tca gca gca gct gct atc aac ctt ggt cgt gct gac 1104Gly Gly Gly Asp Ser Ala Ala Ala Ala Ile Asn Leu Gly Arg Ala Asp
355 360 365aaa ttc tca tgg atc tct act ggt ggt gga gca agc atg gaa ttg ctc 1152Lys Phe Ser Trp Ile Ser Thr Gly Gly Gly Ala Ser Met Glu Leu Leu
370 375 380gaa ggt aaa gta tta cca ggt ttg gca gca ttg act gaa aaa taa 1197Glu Gly Lys Val Leu Pro Gly Leu Ala Ala Leu Thr Glu Lys385 390 395<210>4<211>398<212>PRT<213>B组链球菌<400>4Met Ala Lys Leu Thr Val Lys Asp Val Asp Leu Lys Val Lys Lys Val1 5 10 15Leu Val Arg Val Asp Phe Asn Val Pro Leu Lys Asp Gly Val Ile Thr
20 25 30Asn Asp Asn Arg Ile Thr Ala Ala Leu Pro Thr Ile Lys Tyr Ile Ile
35 40 45Glu Gln Gly Gly Arg Ala Ile Leu Phe Ser His Leu Gly Arg Val Lys
50 55 60Glu Glu Ala Asp Lys Glu Gly Lys Ser Leu Ala Pro Val Ala Ala Asp65 70 75 80Leu Ala Ala Lys Leu Gly Gln Asp Val Val Phe Pro Gly Val Thr Arg
85 90 95Gly Ala Lys Leu Glu Glu Ala Ile Asn Ala Leu Glu Asp Gly Gln Val
100 105 110Leu Leu Val Glu Asn Thr Arg Phe Glu Asp Val Asp Gly Lys Lys Glu
115 120 125Ser Lys Asn Asp Glu Glu Leu Gly Lys Tyr Trp Ala Ser Leu Gly Asp
130 135 140Gly Ile Phe Val Asn Asp Ala Phe Gly Thr Ala His Arg Ala His Ala145 150 155 160Ser Asn Val Gly Ile Ser Ala Asn Val Glu Lys Ala Val Ala Gly Phe
165 170 175Leu Leu Glu Asn Glu Ile Ala Tyr Ile Gln Glu Ala Val Glu Thr Pro
180 185 190Glu Arg Pro Phe Val Ala Ile Leu Gly Gly Ser Lys Val Ser Asp Lys
195 200 205Ile Gly Val Ile Glu Asn Leu Leu Glu Lys Ala Asp Lys Val Leu Ile
210 215 220Gly Gly Gly Met Thr Tyr Thr Phe Tyr Lys Ala Gln Gly Ile Glu Ile225 230 235 240Gly Asn Ser Leu Val Glu Glu Asp Lys Leu Asp Val Ala Lys Asp Leu
245 250 255Leu Glu Lys Ser Asn Gly Lys Leu Ile Leu Pro Val Asp Ser Lys Glu
260 265 270Ala Asn Ala Phe Ala Gly Tyr Thr Glu Val Arg Asp Thr Glu Gly Glu
275 280 285Ala Val Ser Glu Gly Phe Leu Gly Leu Asp Ile Gly Pro Lys Ser Ile
290 295 300Ala Lys Phe Asp Glu Ala Leu Thr Gly Ala Lys Thr Val Val Trp Asn305 310 315 320Gly Pro Met Gly Val Phe Glu Asn Pro Asp Phe Gln Ala Gly Thr Ile
325 330 335Gly Val Met Asp Ala Ile Val Lys Gln Pro Gly Val Lys Ser Ile Ile
340 345 350Gly Gly Gly Asp Ser Ala Ala Ala Ala Ile Asn Leu Gly Arg Ala Asp
355 360 365Lys Phe Ser Trp Ile Ser Thr Gly Gly Gly Ala Ser Met Glu Leu Leu
370 375 380Glu Gly Lys Val Leu Pro Gly Leu Ala Ala Leu Thr Glu Lys385 390 395<210>5<211>516<212>DNA<213>B组链球菌<220><221>CDS<222>(1)..(516)<400>5atg aca cat att aca ttt gac tta ttc aaa gtc ttg ggt caa ttt gta 48Met Thr His Ile Thr Phe Asp Leu Phe Lys Val Leu Gly Gln Phe Val1 5 10 15ggc gaa cac gag tta gac tac cta cca cca caa gta agt gca gca gat 96Gly Glu His Glu Leu Asp Tyr Leu Pro Pro Gln Val Ser Ala Ala Asp
20 25 30gct ttc ctt cgt caa ggg act ggt cct gga tca gat ttt ctc gga tgg 144Ala Phe Leu Arg Gln Gly Thr Gly Pro Gly Ser Asp Phe Leu Gly Trp
35 40 45atg gaa cct cca gaa aac tat gac aaa gaa gaa ttt tct cgc att caa 192Met Glu Pro Pro Glu Asn Tyr Asp Lys Glu Glu Phe Ser Arg Ile Gln
50 55 60aaa gcc gct gaa aag att aaa tca gat agc gaa gta ctc gtg gtt att 240Lys Ala Ala Glu Lys Ile Lys Ser Asp Ser Glu Val Leu Val Val Ile65 70 75 80ggt att ggt ggt tcg tac ctt ggt gca aaa gca gca att gac ttt ttg 288Gly Ile Gly Gly Ser Tyr Leu Gly Ala Lys Ala Ala Ile Asp Phe Leu
85 90 95aat aat cat ttt gct aat ttg caa acc gca gaa gaa cgt aaa gcg cct 336Asn Asn His Phe Ala Asn Leu Gln Thr Ala Glu Glu Arg Lys Ala Pro
100 105 110cag att ctt tat gct gga aat tct att tca tct act tac ctt gcc gat 384Gln Ile Leu Tyr Ala Gly Asn Ser Ile Ser Ser Thr Tyr Leu Ala Asp
115 120 125tta gtt gaa tac gtc caa gat aaa gaa ttc tca gta aat gtc att tca 432Leu Val Glu Tyr Val Gln Asp Lys Glu Phe Ser Val Asn Val Ile Ser
130 135 140aaa tca ggt aca aca act gaa cca gcg att gct ttc cgt gta ttt aaa 480Lys Ser Gly Thr Thr Thr Glu Pro Ala Ile Ala Phe Arg Val Phe Lys145 150 155 160gaa ctt cta gtt aaa aag tac cgg tca aga aga agc 516Glu Leu Leu Val Lys Lys Tyr Arg Ser Arg Arg Ser165 170<210>6<211>172<212>PRT<213>B组链球菌<400>6Met Thr His Ile Thr Phe Asp Leu Phe Lys Val Leu Gly Gln Phe Val1 5 10 15Gly Glu His Glu Leu Asp Tyr Leu Pro Pro Gln Val Ser Ala Ala Asp
20 25 30Ala Phe Leu Arg Gln Gly Thr Gly Pro Gly Ser Asp Phe Leu Gly Trp
35 40 45Met Glu Pro Pro Glu Asn Tyr Asp Lys Glu Glu Phe Ser Arg Ile Gln
50 55 60Lys Ala Ala Glu Lys Ile Lys Ser Asp Ser Glu Val Leu Val Val Ile65 70 75 80Gly Ile Gly Gly Ser Tyr Leu Gly Ala Lys Ala Ala Ile Asp Phe Leu
85 90 95Asn Asn His Phe Ala Asn Leu Gln Thr Ala Glu Glu Arg Lys Ala Pro
100 105 110Gln Ile Leu Tyr Ala Gly Asn Ser Ile Ser Ser Thr Tyr Leu Ala Asp
115 120 125Leu Val Glu Tyr Val Gln Asp Lys Glu Phe Ser Val Asn Val Ile Ser
130 135 140Lys Ser Gly Thr Thr Thr Glu Pro Ala Ile Ala Phe Arg Val Phe Lys145 150 155 160Glu Leu Leu Val Lys Lys Tyr Arg Ser Arg Arg Ser
165 170<210>7<211>318<212>DNA<213>B组链球菌<220><221>CDS<222>(1)..(318)<400>7att aac cga aga ttt aga tgg tct tgg tta tct tca aga aaa gat gta 48Ile Asn Arg Arg Phe Arg Trp Ser Trp Leu Ser Ser Arg Lys Asp Val1 5 10 15gat ttt gtt aat aaa aaa gca aca gat ggt gtg ctt ctt gct cat aca 96Asp Phe Val Asn Lys Lys Ala Thr Asp Gly Val Leu Leu Ala His Thr
20 25 30gat ggt ggg gtt cca aat atg ttt gta acg ctt cct aca caa gac gct 144Asp Gly Gly Val Pro Asn Met Phe Val Thr Leu Pro Thr Gln Asp Ala
35 40 45tac act ctt ggt tac act att tac ttc ttt gag tta gca att ggc ctt 192Tyr Thr Leu Gly Tyr Thr Ile Tyr Phe Phe Glu Leu Ala Ile Gly Leu
50 55 60tca ggt tat ctt aac tca gta aat cca ttt gat caa ccg ggg gta gaa 240Ser Gly Tyr Leu Asn Ser Val Asn Pro Phe Asp Gln Pro Gly Val Glu65 70 75 80gca tat aaa cgt aat atg ttc gca ttt ggt aaa cct gga ttc gaa gag 288Ala Tyr Lys Arg Asn Met Phe Ala Phe Gly Lys Pro Gly Phe Glu Glu
85 90 95ctt agc gct gaa ttg aat gca cgt ctt taa 318Leu Ser Ala Glu Leu Asn Ala Arg Leu
100 105<210>8<211>105<212>PRT<213>B组链球菌<400>8Ile Asn Arg Arg Phe Arg Trp Ser Trp Leu Ser Ser Arg Lys Asp Val1 5 10 15Asp Phe Val Asn Lys Lys Ala Thr Asp Gly Val Leu Leu Ala His Thr
20 25 30Asp Gly Gly Val Pro Asn Met Phe Val Thr Leu Pro Thr Gln Asp Ala
35 40 45Tyr Thr Leu Gly Tyr Thr Ile Tyr Phe Phe Glu Leu Ala Ile Gly Leu
50 55 60Ser Gly Tyr Leu Asn Ser Val Asn Pro Phe Asp Gln Pro Gly Val Glu65 70 75 80Ala Tyr Lys Arg Asn Met Phe Ala Phe Gly Lys Pro Gly Phe Glu Glu
85 90 95Leu Ser Ala Glu Leu Asn Ala Arg Leu
100 105<210>9<211>804<212>DNA<213>B组链球菌<220><221>CDS<222>(1)..(804)<400>9atg aca tta tta gaa aaa att aat gag act aga gac ttt ttg caa gca 48Met Thr Leu Leu Glu Lys Ile Asn Glu Thr Arg Asp Phe Leu Gln Ala1 5 10 15aaa ggc gtc aca gca cca gaa ttt ggy ctt att tta ggc tct ggt tta 96Lys Gly Val Thr Ala Pro Glu Phe Xaa Leu Ile Leu Gly Ser Gly Leu
20 25 30gga gaa ttg gct gaa gaa atc gaa aat cct att gtt gtg gat tat gca 144Gly Glu Leu Ala Glu Glu Ile Glu Asn Pro Ile Val Val Asp Tyr Ala
35 40 45gac atc ccm aat tgg gga cag tca aca gta gtt ggt cat gct gga aaa 192Asp Ile Xaa Asn Trp Gly Gln Ser Thr Val Val Gly His Ala Gly Lys
50 55 60ttt agt gta tgg gat tta tca ggc cgt aag gta tta gcg ctt caa ggt 240Phe Ser Val Trp Asp Leu Ser Gly Arg Lys Val Leu Ala Leu Gln Gly65 70 75 80cgt ttt cat ttt tay gaa ggw aat aca atg gaa gtc gtt act ttc cca 288Arg Phe His Phe Tyr Glu Xaa Asn Thr Met Glu Val Val Thr Phe Pro
85 90 95gta cgt atc atg aga gca ttg gct tgc cac agt gtg ctt gtg act aat 336Val Arg Ile Met Arg Ala Leu Ala Cys His Sar Val Leu Val Thr Asn
100 105 110gca gcg ggt ggg att gga tac gga cca gga act tta atg ctg atc aaa 384Ala Ala Gly Gly Ile Gly Tyr Gly Pro Gly Thr Leu Met Leu Ile Lys
115 120 125gac cac atc aat atg att ggg act aac cct ctc ata ggt gag aac ctt 432Asp His Ile Asn Met Ile Gly Thr Asn Pro Leu Ile Gly Glu Asn Leu
130 135 140gaa gaa ttt gga cca cgt ttc cca gac atg tcg gat gct tay aca gca 480Glu Glu Phe Gly Pro Arg Phe Pro Asp Met Ser Asp Ala Tyr Thr Ala145 150 155 160aca tat cga caa aaa gct cac caa att gct gaa aac gat atc aaa ctc 528Thr Tyr Arg Gln Lys Ala His Gln Ile Ala Glu Asn Asp Ile Lys Leu
165 170 175gaa gaa ggt gtg tac ttg ggt gta tca gga ccc act tat gaa aca cct 576Glu Glu Gly Val Tyr Leu Gly Val Ser Gly Pro Thr Tyr Glu Thr Pro
180 185 190gca gaa att cgt gca ttc caa aca atg ggc gca caa gcg gta ggt atg 624Ala Glu Ile Arg Ala Phe Gln Thr Met Gly Ala Gln Ala Val Gly Met
195 200 205tcc acg gtt cca gag gtg atc gtt gca gct cac tca ggg ctt aaa gtg 672Ser Thr Val Pro Glu Val Ile Val Ala Ala His Ser Gly Leu Lys Val
210 215 220tta gga att tca gca att act aac ctt gcc gct ggc ttc caa tca gag 720Leu Gly Ile Ser Ala Ile Thr Asn Leu Ala Ala Gly Phe Gln Ser Glu225 230 235 240ctc aat cat gag gag gtc gtt gaa gtt act cag cgt att aaa gaa gat 768Leu Asn His Glu Glu Val Val Glu Val Thr Gln Arg Ile Lys Glu Asp
245 250 255ttc aag gga tta ggt aaa tca tta gtt gct gaa ctc 804Phe Lys Gly Leu Gly Lys Ser Leu Val Ala Glu Leu
260 265<210>10<211>268<212>PRT<213>B组链球菌<400>10Met Thr Leu Leu Glu Lys Ile Asn Glu Thr Arg Asp Phe Leu Gln Ala1 5 10 15Lys Gly Val Thr Ala Pro Glu Phe Xaa Leu Ile Leu Gly Ser Gly Leu
20 25 30Gly Glu Leu Ala Glu Glu Ile Glu Asn Pro Ile Val Val Asp Tyr Ala
35 40 45Asp Ile Xaa Asn Trp Gly Gln Ser Thr Val Val Gly His Ala Gly Lys
50 55 60Phe Ser Val Trp Asp Leu Ser Gly Arg Lys Val Leu Ala Leu Gln Gly65 70 75 80Arg Phe His Phe Tyr Glu Xaa Asn Thr Met Glu Val Val Thr Phe Pro
85 90 95Val Arg Ile Met Arg Ala Leu Ala Cys His Ser Val Leu Val Thr Asn
100 105 110Ala Ala Gly Gly Ile Gly Tyr Gly Pro Gly Thr Leu Met Leu Ile Lys
115 120 125Asp His Ile Asn Met Ile Gly Thr Asn Pro Leu Ile Gly Glu Asn Leu
130 135 140Glu Glu Phe Gly Pro Arg Phe Pro Asp Met Ser Asp Ala Tyr Thr Ala145 150 155 160Thr Tyr Arg Gln Lys Ala His Gln Ile Ala Glu Asn Asp Ile Lys Leu
165 170 175Glu Glu Gly Val Tyr Leu Gly Val Ser Gly Pro Thr Tyr Glu Thr Pro
180 185 190Ala Glu Ile Arg Ala Phe Gln Thr Met Gly Ala Gln Ala Val Gly Met
195 200 205Ser Thr Val Pro Glu Val Ile Val Ala Ala His Ser Gly Leu Lys Val
210 215 220Leu Gly Ile Ser Ala Ile Thr Asn Leu Ala Ala Gly Phe Gln Ser Glu225 230 235 240Leu Asn His Glu Glu Val Val Glu Val Thr Gln Arg Ile Lys Glu Asp
245 250 255Phe Lys Gly Leu Gly Lys Ser Leu Val Ala Glu Leu
260 265<210>11<211>1428<212>DNA<213>B组链球菌<220><221>CDS<222>(1)..(1428)<400>11ttg aca aaa gaa tat caa aat tat gtc aat ggc gaa tgg aaa tca tct 48Leu Thr Lys Glu Tyr Gln Asn Tyr Val Asn Gly Glu Trp Lys Ser Ser1 5 10 15gtt aat cag att gag att ttg tca cca att gat gat tct tca ttg gga 96Val Asn Gln Ile Glu Ile Leu Ser Pro Ile Asp Asp Ser Ser Leu Gly
20 25 30ttc gtg cca gcg atg act cga gaa gaa gtt gat cat gct atg aaa gcg 144Phe Val Pro Ala Met Thr Arg Glu Glu Val Asp His Ala Met Lys Ala
35 40 45ggt cgt gag gct tta cca gct tgg gct gct tta aca gta tat gaa cgt 192Gly Arg Glu Ala Leu Pro Ala Trp Ala Ala Leu Thr Val Tyr Glu Arg
50 55 60gca caa tac ctt cat aaa gcc gca gac att att gaa cgt gat aaa gaa 240Ala Gln Tyr Leu His Lys Ala Ala Asp Ile Ile Glu Arg Asp Lys Glu65 70 75 80gaa att gct act gtt tta gca aaa gaa att tct aaa gct tac aat gct 288Glu Ile Ala Thr Val Leu Ala Lys Glu Ile Ser Lys Ala Tyr Asn Ala
85 90 95tca gta act gag gtt gta agg aca gct gat ctt att cgt tat gca gca 336Ser Val Thr Glu Val Val Arg Thr Ala Asp Leu Ile Arg Tyr Ala Ala
100 105 110gaa gaa gga att cgt tta tca act tca gct gac gaa ggt gga aaa atg 384Glu Glu Gly Ile Arg Leu Ser Thr Set Ala Asp Glu Gly Gly Lys Met
115 120 125gat gct tca aca ggt cat aag ttg gct gtt att cgt cgt caa cca gta 432Asp Ala Ser Thr Gly His Lys Leu Ala Val Ile Arg Arg Gln Pro Val
130 135 140ggt atc gtt tta gca atc gca cct tat aat tac cct gtt aac ctc tca 480Gly Ile Val Leu Ala Ile Ala Pro Tyr Asn Tyr Pro Val Asn Leu Set145 150 155 160gga tca aaa att gcg cca gct cta att ggt gga aac gtt gtg atg ttt 528Gly Set Lys Ile Ala Pro Ala Leu Ile Gly Gly Asn Val Val Met Phe
165 170 175aaa cca cca aca caa ggt tca gtc tca gga ctt gtt tta gca aaa gct 576Lys Pro Pro Thr Gln Gly Set Val Ser Gly Leu Val Leu Ala Lys Ala
180 185 190ttt gca gaa gca ggt ctt cca gca ggt gtc ttt aat act att aca gga 624Phe Ala Glu Ala Gly Leu Pro Ala Gly Val Phe Asn Thr Ile Thr Gly
195 200 205cgc ggt tct gag att gga gat tac att gtt gag cat gaa gaa gtt aat 672Arg Gly Set Glu Ile Gly Asp Tyr Ile Val Glu His Glu Glu Val Asn
210 215 220ttt att aac ttt aca gga tca acg cca gtt gga caa cgt att ggt aag 720Phe Ile Asn Phe Thr Gly Ser Thr Pro Val Gly Gln Arg Ile Gly Lys225 230 235 240ttg gca gga atg cgt cca att atg ctt gag ttg ggc ggt aag gat gca 768Leu Ala Gly Met Arg Pro Ile Met Leu Glu Leu Gly Gly Lys Asp Ala
245 250 255ggt atc gtc tta gct gat gct gac ctt gat aac gct gct aaa caa atc 816Gly Ile Val Leu Ala Asp Ala Asp Leu Asp Asn Ala Ala Lys Gln Ile
260 265 270gtt gca ggt gct tat gat tac tct gga caa cgc tgt acg gca att aag 864Val Ala Gly Ala Tyr Asp Tyr Ser Gly Gln Arg Cys Thr Ala Ile Lys
275 280 285cgt gtg ctt gtc gtt gaa gaa gtt gcw gat gaa ttg gca gaa aaa ata 912Arg Val Leu Val Val Glu Glu Val Xaa Asp Glu Leu Ala Glu Lys Ile
290 295 300tct gaa aat gta gca aaa tta tca gta ggt gat cca ttt gat aat gca 960Ser Glu Asn Val Ala Lys Leu Ser Val Gly Asp Pro Phe Asp Asn Ala305 310 315 320acg gtg aca ccg gtt att gat gat aat tca gct gac ttt att gaa agc 1008Thr Val Thr Pro Val Ile Asp Asp Asn Ser Ala Asp Phe Ile Glu Ser
325 330 335tta gta gta gat gca cgt caa aaa ggt gcg aaa gaa ttg aat gaa ttt 1056Leu Val Val Asp Ala Arg Gln Lys Gly Ala Lys Glu Leu Asn Glu Phe
340 345 350aaa cgt gat ggt cgt cta tta act cca gga ttg ttt gat cat gtt act 1104Lys Arg Asp Gly Arg Leu Leu Thr Pro Gly Leu Phe Asp His Val Thr
355 360 365tta gat atg aaa cta gct tgg gaa gag cct ttt gga cca att ctc cca 1152Leu Asp Met Lys Leu Ala Trp Glu Glu Pro Phe Gly Pro Ile Leu Pro
370 375 380att att cgt gtc aag gat gca gaa gaa gct gtt gct att gcc aac aaa 1200Ile Ile Arg Val Lys Asp Ala Glu Glu Ala Val Ala Ile Ala Asn Lys385 390 395 400tct gat ttt gga tta caa tca tca gtc ttt aca cgt gat ttc caa aaa 1248Ser Asp Phe Gly Leu Gln Ser Ser Val Phe Thr Arg Asp Phe Gln Lys
405 410 415gca ttt gat ata gca aat aaa ctt gaa gtt ggt aca gtt cac att aac 1296Ala Phe Asp Ile Ala Asn Lys Leu Glu Val Gly Thr Val His Ile Asn
420 425 430aat aag act gga cgt ggt ccw gat aat ttc cca ttc tta gga ctc aaa 1344Asn Lys Thr Gly Arg Gly Xaa Asp Asn Phe Pro Phe Leu Gly Leu Lys
435 440 445gga tct ggt gca ggt gtt caa ggt atc aga tat tca att gaa gca atg 1392Gly Ser Gly Ala Gly Val Gln Gly Ile Arg Tyr Ser Ile Glu Ala Met
450 455 460aca aat gta aaa tcg att gtt ctc gat atg aaa tag 1428Thr Asn Val Lys Ser Ile Val Leu Asp Met Lys465 470 475<210>12<211>475<212>PRT<213>B组链球菌<400>12Leu Thr Lys Glu Tyr Gln Asn Tyr Val Asn Gly Glu Trp Lys Ser Ser1 5 10 15Val Asn Gln Ile Glu Ile Leu Ser Pro Ile Asp Asp Ser Ser Leu Gly
20 25 30Phe Val Pro Ala Met Thr Arg Glu Glu Val Asp His Ala Met Lys Ala
35 40 45Gly Arg Glu Ala Leu Pro Ala Trp Ala Ala Leu Thr Val Tyr Glu Arg
50 55 60Ala Gln Tyr Leu His Lys Ala Ala Asp Ile Ile Glu Arg Asp Lys Glu65 70 75 80Glu Ile Ala Thr Val Leu Ala Lys Glu Ile Ser Lys Ala Tyr Asn Ala
85 90 95Ser Val Thr Glu Val Val Arg Thr Ala Asp Leu Ile Arg Tyr Ala Ala
100 105 110Glu Glu Gly Ile Arg Leu Ser Thr Ser Ala Asp Glu Gly Gly Lys Met
115 120 125Asp Ala Ser Thr Gly His Lys Leu Ala Val Ile Arg Arg Gln Pro Val
130 135 140Gly Ile Val Leu Ala Ile Ala Pro Tyr Asn Tyr Pro Val Asn Leu Ser145 150 155 160Gly Ser Lys Ile Ala Pro Ala Leu Ile Gly Gly Asn Val Val Met Phe
165 170 175Lys Pro Pro Thr Gln Gly Ser Val Ser Gly Leu Val Leu Ala Lys Ala
180 185 190Phe Ala Glu Ala Gly Leu Pro Ala Gly Val Phe Asn Thr Ile Thr Gly
195 200 205Arg Gly Ser Glu Ile Gly Asp Tyr Ile Val Glu His Glu Glu Val Asn
210 215 220Phe Ile Asn Phe Thr Gly Ser Thr Pro Val Gly Gln Arg Ile Gly Lys225 230 235 240Leu Ala Gly Met Arg Pro Ile Met Leu Glu Leu Gly Gly Lys Asp Ala
245 250 255Gly Ile Val Leu Ala Asp Ala Asp Leu Asp Asn Ala Ala Lys Gln Ile
260 265 270Val Ala Gly Ala Tyr Asp Tyr Ser Gly Gln Arg Cys Thr Ala Ile Lys
275 280 285Arg Val Leu Val Val Glu Glu Val Xaa Asp Glu Leu Ala Glu Lys Ile
290 295 300Ser Glu Asn Val Ala Lys Leu Ser Val Gly Asp Pro Phe Asp Asn Ala305 310 315 320Thr Val Thr Pro Val Ile Asp Asp Asn Ser Ala Asp Phe Ile Glu Ser
325 330 335Leu Val Val Asp Ala Arg Gln Lys Gly Ala Lys Glu Leu Asn Glu Phe
340 345 350Lys Arg Asp Gly Arg Leu Leu Thr Pro Gly Leu Phe Asp His Val Thr
355 360 365Leu Asp Met Lys Leu Ala Trp Glu Glu Pro Phe Gly Pro Ile Leu Pro
370 375 380Ile Ile Arg Val Lys Asp Ala Glu Glu Ala Val Ala Ile Ala Asn Lys385 390 395 400Ser Asp Phe Gly Leu Gln Ser Ser Val Phe Thr Arg Asp Phe Gln Lys
405 410 415Ala Phe Asp Ile Ala Asn Lys Leu Glu Val Gly Thr Val His Ile Asn
420 425 430Asn Lys Thr Gly Arg Gly Xaa Asp Asn Phe Pro Phe Leu Gly Leu Lys
435 440 445Gly Ser Gly Ala Gly Val Gln Gly Ile Arg Tyr Ser Ile Glu Ala Met
450 455 460Thr Asn Val Lys Ser Ile Val Leu Asp Met Lys465 470 475
Claims (12)
1.一种由包括任一已被鉴定为MS4，MS10，MS11，MS14和MS16的可获自B组链球菌的基因或其同源物或功能性片段的操纵子所编码的肽。
2.根据权利要求1的肽，其任一氨基酸序列为已确定的SEQ ID NOS.2，4，6，8，10和12。
3.根据权利要求1或2的肽，其用于医疗用途。
4.编码权利要求1或2的肽的多核苷酸，其用于医疗用途。
5.一种被转化以表达权利要求1或2的肽的宿主。
6.包含权利要求1或2的肽的疫苗，或用于其表达的工具。
7.权利要求1-5中任一权利要求的产物的用途，用于潜在药物筛选或毒性检测。
8.权利要求1-5中任一权利要求的产物的用途，用于与细菌感染相关的疾病治疗或预防的药物的制造。
9.根据权利要求8的用途，其中的感染是B组链球菌感染。
10.根据权利要求8或9的用途，其中的感染是病灶性感染。
11.根据权利要求8或9的用途，其中的感染是尿道感染。
12.一种抗权利要求1或2的肽的抗体。
Applications Claiming Priority (12)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9828346.8A GB9828346D0 (en) | 1998-12-22 | 1998-12-22 | Protein and compositions containing it |
| GB9828346.8 | 1998-12-22 | ||
| GBGB9901233.8A GB9901233D0 (en) | 1999-01-20 | 1999-01-20 | Protein and compositions containing it |
| GB9901234.6 | 1999-01-20 | ||
| GBGB9901234.6A GB9901234D0 (en) | 1999-01-20 | 1999-01-20 | Protein and compositions containing it |
| GB9901233.8 | 1999-01-20 | ||
| GB9908321.4 | 1999-04-12 | ||
| GBGB9908321.4A GB9908321D0 (en) | 1999-04-12 | 1999-04-12 | Purine nucleoside phosphatase and compositions containing it |
| GB9912036.2 | 1999-05-24 | ||
| GBGB9912036.2A GB9912036D0 (en) | 1999-05-24 | 1999-05-24 | Glucose-6-phosphate isomerase and compositions containing it |
| GB9922596.3 | 1999-09-23 | ||
| GBGB9922596.3A GB9922596D0 (en) | 1999-09-23 | 1999-09-23 | Protein and compositions containing it |
Related Child Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2005100047117A Division CN1733800A (zh) | 1998-12-22 | 1999-12-22 | 外表面蛋白质及其基因和用途 |
| CNA2008101761856A Division CN101486756A (zh) | 1998-12-22 | 1999-12-22 | 外表面蛋白质及其基因和用途 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1357045A true CN1357045A (zh) | 2002-07-03 |
Family
ID=27547330
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2008101761856A Pending CN101486756A (zh) | 1998-12-22 | 1999-12-22 | 外表面蛋白质及其基因和用途 |
| CNA2005100047117A Pending CN1733800A (zh) | 1998-12-22 | 1999-12-22 | 外表面蛋白质及其基因和用途 |
| CN99814781A Pending CN1357045A (zh) | 1998-12-22 | 1999-12-22 | 外表面蛋白质及其基因和用途 |
Family Applications Before (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2008101761856A Pending CN101486756A (zh) | 1998-12-22 | 1999-12-22 | 外表面蛋白质及其基因和用途 |
| CNA2005100047117A Pending CN1733800A (zh) | 1998-12-22 | 1999-12-22 | 外表面蛋白质及其基因和用途 |
Country Status (24)
| Country | Link |
|---|---|
| US (3) | US7217415B1 (zh) |
| EP (2) | EP1140994B1 (zh) |
| JP (1) | JP2002533065A (zh) |
| KR (4) | KR100866170B1 (zh) |
| CN (3) | CN101486756A (zh) |
| AP (1) | AP2006003504A0 (zh) |
| AT (1) | ATE297995T1 (zh) |
| AU (1) | AU758722B2 (zh) |
| BR (1) | BR9916473A (zh) |
| CA (1) | CA2354843A1 (zh) |
| CZ (1) | CZ20012174A3 (zh) |
| DE (1) | DE69925866T2 (zh) |
| DK (1) | DK1140994T3 (zh) |
| EA (1) | EA009885B1 (zh) |
| ES (1) | ES2241352T3 (zh) |
| HK (1) | HK1039339A1 (zh) |
| HU (1) | HUP0201022A3 (zh) |
| NO (1) | NO20013101L (zh) |
| NZ (4) | NZ525538A (zh) |
| OA (1) | OA12425A (zh) |
| PL (1) | PL351027A1 (zh) |
| PT (1) | PT1140994E (zh) |
| SI (1) | SI1140994T1 (zh) |
| WO (1) | WO2000037490A2 (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103060284A (zh) * | 2012-10-31 | 2013-04-24 | 内蒙古民族大学 | 一种无乳链球菌pgk亚单位重组蛋白及其制备方法 |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EA009885B1 (ru) * | 1998-12-22 | 2008-04-28 | Майкросайенс Лимитед | Применение пептидов бактерий streptococcus группы b, кодирующего их полинуклеотида, вакцина и антитело |
| US6890539B2 (en) * | 1998-12-22 | 2005-05-10 | Microscience, Ltd. | Genes and proteins, and their use |
| AP1502A (en) * | 1998-12-22 | 2005-12-20 | Microscience Ltd | Genes and proteins, and their uses. |
| EP2104512A2 (en) * | 2006-12-21 | 2009-09-30 | Emergent Product Development UK Limited | Streptococcus proteins, and their use in vaccination |
| CN110669711A (zh) * | 2019-08-09 | 2020-01-10 | 中国水产科学研究院珠江水产研究所 | 基于pgk基因的重组乳酸乳球菌和无乳链球菌病疫苗 |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0230777B1 (en) | 1985-12-28 | 1991-04-10 | Ohgen Research Laboratories Ltd., | Antitumor protein gene of streptococcus pyogenes su, plasmids containing the gene, transformant cells harboring the plasmids, and process for producing the antitumor protein |
| US5328996A (en) * | 1989-03-29 | 1994-07-12 | University Of Florida Research Foundation, Inc. | Bacterial plasmin receptors as fibrinolytic agents |
| EP0672123A1 (en) * | 1992-01-08 | 1995-09-20 | The Rockefeller University | Multifunctional surface protein of streptococci |
| IL107458A0 (en) * | 1992-11-02 | 1994-02-27 | Gen Hospital Corp | Conjugate vaccine against group b streptococcus |
| US6015889A (en) * | 1993-03-19 | 2000-01-18 | Gunnar Lindahl | Protein rib, a cell surface protein that confers immunity to many strains of the group B streptococcus: process for purification of the protein, reagent kit and pharmaceutical composition |
| SG47049A1 (en) | 1993-03-19 | 1998-03-20 | Gunnar Lindahl | Protein rib a cell surface protein that confers immunity to manu strains of the group b strepto-ccus process for purification of the protein reagent kit |
| US6346392B1 (en) * | 1996-11-27 | 2002-02-12 | Smithkline Beecham Corporation | Polynucleotides encoding a novel glutamine transport ATP-binding protein |
| AU5194598A (en) * | 1996-10-31 | 1998-05-22 | Human Genome Sciences, Inc. | (streptococcus pneumoniae) antigens and vaccines |
| US7196164B2 (en) * | 1997-07-08 | 2007-03-27 | Human Genome Sciences, Inc. | Secreted protein HHTLF25 |
| US7129340B1 (en) * | 1997-07-02 | 2006-10-31 | sanofi pasteur limited/sanofi pasteur limitée | Nucleic acid and amino acid sequences relating to streptococcus pneumoniae for diagnostics and therapeutics |
| US6800744B1 (en) * | 1997-07-02 | 2004-10-05 | Genome Therapeutics Corporation | Nucleic acid and amino acid sequences relating to Streptococcus pneumoniae for diagnostics and therapeutics |
| US6380370B1 (en) * | 1997-08-14 | 2002-04-30 | Genome Therapeutics Corporation | Nucleic acid and amino acid sequences relating to Staphylococcus epidermidis for diagnostics and therapeutics |
| US6165763A (en) * | 1997-10-30 | 2000-12-26 | Smithkline Beecham Corporation | Ornithine carbamoyltransferase |
| US6248329B1 (en) * | 1998-06-01 | 2001-06-19 | Ramaswamy Chandrashekar | Parasitic helminth cuticlin nucleic acid molecules and uses thereof |
| US6890539B2 (en) * | 1998-12-22 | 2005-05-10 | Microscience, Ltd. | Genes and proteins, and their use |
| AP1502A (en) * | 1998-12-22 | 2005-12-20 | Microscience Ltd | Genes and proteins, and their uses. |
| EA009885B1 (ru) * | 1998-12-22 | 2008-04-28 | Майкросайенс Лимитед | Применение пептидов бактерий streptococcus группы b, кодирующего их полинуклеотида, вакцина и антитело |
| US6605709B1 (en) * | 1999-04-09 | 2003-08-12 | Genome Therapeutics Corporation | Nucleic acid and amino acid sequences relating to Proteus mirabilis for diagnostics and therapeutics |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103060284A (zh) * | 2012-10-31 | 2013-04-24 | 内蒙古民族大学 | 一种无乳链球菌pgk亚单位重组蛋白及其制备方法 |
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