CN101066447A - 基因和蛋白质,及它们的用途 - Google Patents
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Abstract
本发明涉及基因和蛋白质及它们的用途。根据本发明,在B群链球菌中鉴定一系列基因,其产物可能与生物体的外表面结合。该基因或其功能性片段在制备治疗制剂,例如使患者对微生物感染产生免疫的疫苗中可能是有益的。
Description
本案是分案申请,母案申请号为99814780.X(国际申请号为PCT/GB99/04377),申请日为1999年12月22日,发明名称为“基因和蛋白质,及它们的用途”。
发明领域
本发明涉及细菌基因和蛋白质的鉴定和它们的用途。特别是,涉及其在免疫治疗和药物筛选中的用途。
发明背景
B群链球菌(Streptococcus)(GBS),也称为无乳链球菌(streptococcusagalactiae),是多种病症的病原体。特别是,GBS引起:
早发性新生儿感染
这种感染通常始于子宫中,并在婴幼儿中引起严重的败血症和肺炎,如果未治疗则其是致命的,且即使治疗其也与10-20%的死亡率有关。
迟发性新生儿感染
这种感染在出生之后不久直到大约3月龄的一段时间内出现。它引起败血症,在90%的病例中并发有脑膜炎。也发生其它的灶性感染,包括骨髓炎,脓毒性关节炎,脓肿和眼内炎。
成人感染
看来这些愈加普遍,频繁地发生在刚生产婴儿的妇女,年长者和无免疫应答的人中。他们的特征在于败血症和灶性感染,包括骨髓炎,脓毒性关节炎,脓肿和眼内炎。
尿道感染
GBS是尿道感染的一个原因,且在怀孕期间约占所有感染的10%。
兽医感染
GBS在母牛中引起慢性乳腺炎。这又导致牛奶产量减少,并因此消减了相当大的经济价值。
可以用抗生素治疗GBS感染。然而,免疫接种是优选的。因此希望研制一种能够用于治疗有效的疫苗中的免疫原。
发明概述
本发明是基于GBS中一系列基因的鉴定,并与生物体相关,其产物可以位于生物体的外表面并因此可以作为免疫-治疗的靶使用。
根据本发明的一个方面,肽是由可从B群链球菌中获得的包括任一被鉴定为pho1-13,pho3-21,pho2-15,pho3-18,pho3-22,pho3-3,pho3-17,pho2-2,pho1-5,pho3-1,pho3-23,pho3-50,pho1-14,pho2-10,pho3-14,pho3-24和pho3-29的基因的操纵子或其同源物或其功能性片段编码的。这种肽适宜于治疗用途,例如,当分离时。
此处使用术语“功能性片段”以定义保留完整基因或肽活性的基因或肽的一部分。例如,肽的功能性片段可以作为抗原决定因素使用,其在疫苗或抗体的生产中是有益的。
基因片段可以用于编码活性肽。或者,基因片段可能在基因治疗中有用,在体内靶定野生型基因以发挥治疗作用。
本发明的肽可以包含此处被鉴定为SEQ ID NOS.2,4,6,8,10,11,13,15,17,19,21,23,25,27,29,31,33和35的任一氨基酸序列,或其功能性片段。
由于细胞外或细胞表面定位,对于抗GBS的治疗有效的疫苗的生产,本发明的肽可能是适宜的候选物。术语“治疗有效”的意思是包括疫苗的预防作用。例如,疫苗可以包含用于感染治疗的本发明的肽,或用于其表达的工具。可以在怀孕之前或怀孕过程中将疫苗给予女性以保护母亲和新生儿免受GBS感染。
根据本发明的另一方面,肽或基因可以用于筛选潜在的抗微生物药物或用于毒性的检出。
本发明又一方面是此处鉴定的任一产品用于与B群链球菌菌株感染相关病症的治疗或预防的用途。
虽然已经描述了蛋白质在患者治疗中的用途,认为本发明产品的兽医用途也在本发明的范围之内。特别是,肽或疫苗可以用于慢性乳腺炎,特别是在母牛中的治疗。
发明描述
本发明是根据B群链球菌菌株M732描述的。然而,所有的GBS菌株和许多其它的细菌菌株可能包括具有与M732肽同源的氨基酸序列的相关肽或蛋白质。可能包括这样的肽的生物体包括,但不限于,肺炎链球菌(Streptococcus pneumoniae),酿脓链球菌(Streptococcus pyogenes),猪链球菌(Streptococcussuis),米氏链球菌(Streptococcus milleri),C群和G群链球菌和肠球菌。每种这些生物体的疫苗均可以按照描述GBS的相同方式来研制。
优选地,对于疫苗生产有益的肽具有大于40%的与此处鉴定的肽的序列相似性。更优选,肽具有大于60%的序列相似性。最优选,肽具有远大于80%的序列相似性,例如,95%相似性。
只要表征了本发明的基因,使用基因序列在其它微生物体中确立同源物是可能的。也可能确定是否其它微生物体具有相似的外表面产物。可以通过在现有的数据库,例如EMBL或Genbank中检索来建立序列同源物。
可以通过本领域已知的方法来纯化和分离本发明的肽或蛋白质。特别是,只要鉴定了基因序列,使用重组技术在适宜的宿主中表达基因序列将是可能的。可以鉴定活性片段和同源物,且其在治疗中是有益的。例如,肽或它们的活性片段可以在疫苗中作为抗原决定簇使用,以引起免疫应答。它们也可以在抗体的制备中使用以用于被动免疫或诊断应用,适宜的抗体包括单克隆抗体,或其片段,包括单链fv片段。抗体的制备方法对于本领域的那些技术人员是显而易见的。
基于减毒微生物体的疫苗的制备对于本领域的那些技术人员是已知的。按照治疗中所用的,所需要的或所期望的,可以用适宜的载体或辅剂,例如明矾配制疫苗组合物,以提供对B群链球菌或其它有关微生物体的有效免疫接种。疫苗制剂的制备对于技术人员来说将是显而易见的。
更通常地,并为本领域的那些技术人员所熟知的,为了治疗的用途,可以选择本发明活性组分适宜的量,适宜的载体或赋形剂,和给药途径。可以根据已知的标准,如所治疗病症的性质/严重性,患者的类型或健康状况等,来选择或确定这些因素。
如下鉴定本发明的产品:
使用质粒载体pFW-phoA1,pFW-phoA2和pFW-phoA3(Podbielski,A等人,1996.基因(Gene))177:137-147)制备GBS(M732菌株)染色体DNA的部分基因库。这些质粒具有组成性大观霉素腺苷酰基转移酶抗生素抗性标记,其赋予高水平的大观霉素抵抗力并因此而容易选择。此外,对于碱性磷酸酶,这些载体包含截短的(无前导序列的(leaderless))大肠杆菌phoA基因。与上游符合读框BamI限制酶位点相比较,这三个载体仅仅就无前导序列phoA基因是否存在于读框其中这方面不同。因为此截短的大肠杆菌phoA基因缺乏适当的前导序列以输出此酶穿过细菌膜,所以当质粒在大肠杆菌phoA突变体(例如DH5α菌株)中繁殖时,细胞外的碱性磷酸酶活性是缺乏的。产色的碱性磷酸酶底物,XP(5-溴-4-氯-3-吲哚-磷酸酯),不进入完整的细菌细胞中,因此仅仅可以检测到被输出的或结合于表面的碱性磷酸酶活性。当被输出或结合于表面的碱性磷酸酶活性存在时,产色XP底物被切割以产生蓝色色素,且可以通过它们的蓝颜色鉴定相应的细菌菌落。
用BamHI完全消化质粒DNA并使用虾碱性磷酸酶去磷酸化。用Sau3AI部分地消化GBS基因细DNA,在蔗糖梯度上按大小进行分级分离,将大小<1kb的片段连接到所制备的pFW-phoA载体上。将大肠杆菌菌株DH5α选作克隆宿主,因为它缺少功能性phoA基因。在包含100μg/ml大观霉素和40μg/ml产色XP底物的Luria琼脂上选择重组质粒。包含带GBS***DNA的质粒大肠杆菌转化子是通过菌落的蓝颜色鉴定的,所述***DNA互补了无前导序列phoA基因的输出信号序列。以这种方式筛选了包含GBS***DNA的大约30000不同的重组质粒,互补无前导序列phoA的83个重组质粒用于进一步研究。
从这些实验中选择多种克隆,每种均包含这样的质粒,该质粒包含互补无前导序列phoA的基因(或其一部分)。
一旦在每种克隆中鉴定了基因,那么如下得到完整长度的基因序列是可能的。
为了基因组DNA测序,使用已经鉴定和测序的基因片段设计寡核苷酸引物。设计这些引物以便从得到的序列中以“向外的”方向上测序。一旦读取,检查所得到的序列以了解是否已经到达基因的5’和3’端。这些特征的存在是通过检查同源物序列,以及对于5’端,Shine-Dalgarno共有序列在先的AUG起始密码子(或公认的相等物)的存在,和对于3’端,翻译终止(停止)密码子的存在鉴定的。
一旦完整长度基因得以鉴定,为了完整长度的产品的扩增而设计引物。所使用的引物包括限制酶识别位点(NcoI位于5’端且Eco0109I位于3’端)以让后来的产品克隆入所用的乳球菌(Lactococcal)表达***。
使用引物进行PCR,且将产品克隆入pCR2.1克隆载体(in Vitrogen)。在克隆片段的存在确证之后,使用限制酶NcoI和Eco0109I切断DNA。
片段***其中的载体是一修饰的pNZ8048版本(Kuipers,O.P.等人,(1998)生物技术杂志(J.Biotech))64:15-21)。此载体带有乳球菌复制起点,氯霉素抗性标记,可诱导的乳链菌肽启动子和一种多克隆位点其被用两个10X His标签对多克隆位点的替换而改变所述标签,最5′端侧翼为NcoI位点,中间用多克隆位点分开(包括Eco0109I位点),终止密码子在3’端。
***有关基因,以便10X His标签位于相对于编码区的3’位。重组质粒转化进乳酸乳球菌(L.lactis)(菌株NZ9000-Kuipers,O.P.等人,(1998)同上)之后,准备400ml液体培养物,通过将乳链菌肽加入到培养物中,诱导蛋白质的翻译。培养2小时之后,收获细胞并通过玻珠打浆(bead beating)裂解细胞。通过离心纯化最终的细胞裂解物,然后将其通入金属亲和柱(Talon Clonetech)。在用咪唑洗脱结合蛋白之前,反复洗涤柱子。
为了鉴定包含His标签的重组蛋白级分,用SDS-PAGE,Western印迹分析并用抗His抗体探测源自每一级分的等分试样。
然后将所得到的重组蛋白用于免疫新西兰白兔,免疫之前收获免疫前血清。加强免疫之后,处死白兔并收集血清。此血清用于蛋白质印迹,ELISA和动物保护模型中。
使用从动物研究中获得的血清,进行免疫吸附的研究。
B群链球菌在20ml Todd Hewitt肉汤(THB)中培养8小时,在5ml PBS中收获和重悬浮。50μl的等分试样用于在96孔板(Nunc Immuno-Sorb)中包被孔。在4℃过夜以使细菌吸附于板上。用PBS洗涤板两次,然后在37℃时,在PBS中用3%BSA封闭1小时。再洗涤板。在PBS中产生血清的连续10倍的稀释液,并将50μl的这些稀释液加入到板的孔中,双份。覆盖板并在37℃时培养1小时。洗涤该板,将50μl 1∶5000浓度的抗兔碱性磷酸酶缀合次级抗体加入到每个孔中。37℃培养1小时后,再洗涤该板。将50μl底物(PNPP)加入到每个孔中,在读取405nm处的吸收值之前,让反应进行30分钟。
也进行动物保护的研究以测试在经免疫的兔上的保护效果。
GBS M732在THB中培养直到达到对数中期阶段—大约5个小时。在计数室中计数细胞,稀释得到浓度为2×107个细菌/ml的免疫前血清或测试血清。将50μl经由腹膜内途径注射进0-1日龄的小鼠中。观察到小鼠的存活超过48小时。
下列实施例举例说明本发明。
实施例1
第一个克隆包含在此处被鉴定为SEQ ID NO.1的基因序列,和被鉴定为SEQID NO.2的氨基酸序列,并被分类为pho1-13。
进行pho1-13的氨基酸序列比较。
可以在酿脓链球菌,肺炎链球菌,唾液链球菌(S.salivarius),大肠杆菌,小肠结肠炎耶尔森氏菌(Yersinia enterocolitica),Aquifex aeolicus,幽门螺杆菌(Helicobacter pylori)和流感嗜血杆菌(Haemophilus influenzae)中鉴定GBS pho1-13基因产物的同源物。酿脓链球菌和肺炎链球菌的同源物是从基因细序列数据中鉴定的,且关于基因或基因产物的鉴定,没有注释是可利用的。在所有其它的情况中,上述同源物可以被鉴定为依赖于ATP的Clp蛋白酶蛋白裂解亚基。在ATP和镁存在情况下,Clp蛋白酶的催化活性导致蛋白质水解为小肽(Giffard,P.M.等人1993.普通微生物学杂志(J.Gen.Microbiol.)139:913-920)。此外,已经证明了Clp蛋白酶的ClpP成分被诱导为热激反应的一部分(Kroh,H.E.和L.D.Simon.1990.细菌学杂志(J.Bacteriol).172:6026-6034)且可能此亚基或完全的蛋白裂解结构域与细菌的表面结合。
按照上面描述的进行免疫研究,得到下列结果。
治疗 没有动物 没有动物存活
时间(小时)
24 48
PBS 10 7 0
免疫前 37 13 0
经免疫的 38 17 9
实施例2
选择第二个包括称为pho1-14质粒的克隆。此质粒包括互补无前导序列phoA的基因(或其一部分)。核苷酸和推定的氨基酸序列分别作为SEQ ID NOS.3和4列出。
进行pho1-14的氨基酸序列比较。
可以在酿脓链球菌,粪肠球菌(Enterococcus faecalis)和肺炎链球菌中鉴定GBS pho1-14基因产物的同源物。这些同源物是从基因组序列数据中鉴定的,且关于基因或基因产物的鉴定,没有注释是可利用的。另外,也可以从弗氏志贺氏菌(Shigella flexneri)(SpaR)和假结核耶尔森氏菌(Yersinia pseudotuberculosis)(YscT)中鉴定两种可能的同源物。这后两种同源物是相关蛋白质,认为其在细菌的膜上锚定(Bergman,T1994.细菌学杂志176:2619-2626)。在弗氏志贺氏菌中,已经证明了spaR基因产物对于上皮细胞的入侵是重要的(Sasakawa,C.et al.1993.细菌学杂志175:2334-2346)。此外,spaR基因产物对于侵入质粒抗原的表面呈递来说,也是需要的。在假结核耶尔森氏菌中,类似的蛋白质是Yop分泌***的组成部分,且对于生物体中的毒性也是重要的。
实施例3
选择第三个包括称为pho1-5质粒的克隆。此质粒包括互补无前导序列phoA的基因(或其一部分)。核苷酸和推定的氨基酸序列分别作为SEQ ID NOS.5和6列出。
进行pho1-5的氨基酸序列比较。
仅可以在酿脓链球菌,肉葡萄球菌(Staphylococcus carnosus)(sceA)中鉴定出GBS pho1-5基因产物的同源物。酿脓链球菌同源物是从基因组序列数据中鉴定的,且关于基因或基因产物的鉴定,没有注释是可利用的。此外,在源自肉葡萄球菌的sceA基因产物上,几乎没有信息是可以利用的。SceA基因产物表现出某些与源自加氏乳杆菌(Lactobacillus gasseri)的促集聚蛋白质相似的序列。基于sceA基因产物的分析,此分子包含充分保守的信号序列且其被很显然地分泌或与细菌细胞的表面结合。
实施例4
选择又一个包括称为pho3-3质粒的克隆。此质粒包括补充无前导序列phoA的基因(或其一部分)。核苷酸和推定的氨基酸序列分别作为SEQ ID NOS.7和8列出。
进行pho3-3的氨基酸序列比较。
可以在变异链球菌(Streptococcus mutans)(rmiC),(cpsM)肺炎链球菌和酿脓链球菌中鉴定GBS pho3-3基因产物的同源物。酿脓链球菌同源物是从基因组序列数据中鉴定的,且关于基因或基因产物的鉴定,没有注释是可利用的。在肺炎链球菌中,同源物可以被鉴定为dTDP-4-酮-6-去氧葡萄糖-3,5-差向异构酶。在其它两种情况下,上面的同源物可以被鉴定为dTDP-4-酮-L-鼠李糖还原酶(rmlC)。在变异链球菌中,编码此酶基因的rmlC是rml基因座的一部分。rml基因座包括三种基因,其显示出与参与dTDP-鼠李糖(变异链球菌多糖胶囊中鼠李糖成分的直接前体)的生物合成中的酶显著的相似性(Tsukioka,Y.等人.1997.细菌学杂志.17:73-83)。在肺炎链球菌中鉴定类似的基因座(coffey等人,1998,分子微生物学,17:73-83)。几乎所有的链球菌在它们与多糖有关的细胞壁中特征性地具有鼠李糖(Schleifer,K.H.和R.Kilper-Balz.1987.***应用微生物(Syst.Appl.Microbiol).10:1-19),且在链球菌中,很可能dTDP-4-酮-L鼠李糖还原酶与外表面结合。
实施例5
选择又一个包括称为pho2-10质粒的克隆。此质粒包括互补无前导序列phoA的基因(或其一部分)。
核苷酸序列分别作为SEQ ID NO.9列出。由此,鉴定了上游的和下游的编码区,推定的氨基酸序列作为SEQ ID NOS.10和11列出。
进行pho2-10的氨基酸序列比较。
可以在酿脓链球菌,粪肠球菌,Debaryomyces occidentalis(hatI)和大肠杆菌(trkD)中鉴定GBS pho2-10基因产物的同源物。酿脓链球菌和大肠杆菌同源物是从基因组序列数据中鉴定的,且关于基因或基因产物的鉴定,没有注释是可利用的。在酵母菌D.occidentalis中,hak1基因是源自大肠杆菌的trkD基因的同源物(Banuelos,M.A.等人.1995.EMBO J.14:3012-3027)。大肠杆菌的trkD基因是kup钾摄取***的一部分。此处鉴定的特定同源物是kup***钾摄取蛋白。在大肠杆菌中,kup***是一种组成型钾摄取***。Kup***钾摄取蛋白包含高度疏水的N-端,预测其至少12次跨越膜。Kup不与其他已知的膜蛋白序列同源。没有ATP结合的迹象,并提示通过化学渗透的梯度来推动***(Schleyer,M.&E.P.Bakker,1993.细菌学杂志.175:6925-6931)。
实施例6
选择又一个包括称为pho2-15质粒的克隆。此质粒包括互补无前导序列phoA的基因(或其一部分)。基因的核苷酸和推定氨基酸序列分别作为SEQ ID NOS.12和13列出。
进行pho2-15的氨基酸序列比较。
可以在酿脓链球菌,肺炎链球菌,粪肠球菌和大肠杆菌(gat C和SgcC)中鉴定GBS pho2-15基因产物的同源物。酿脓链球菌,肺炎链球菌和粪肠球菌同源物是从基因组序列数据中鉴定的,且关于基因或基因产物的鉴定,没有注释是可利用的。在大肠杆菌中,gatC和sgcC基因产物可以被鉴定为磷酸烯醇丙酮酸依赖的糖磷酸转移酶***(PTS)(一种重要的碳水化合物活性-运送***)的IIC成分。在PTS***中,IIC成分一般参与细胞外碳水化合物的结合,并与IID成分形成一复合体以组成膜通道(Nobelmann,B.和J.W.Lengeler.1995.生物化学和生物物理学学报(Biochim.Biophys.Acta)1262:69-72)。
实施例7
选择又一个包括称为pho2-2质粒的克隆。此质粒包括互补无前导序列phoA的基因(或其一部分)。基因的核苷酸和推定氨基酸序列分别作为SEQ ID NOS.14和15列出。
进行pho2-2的氨基酸序列比较。
可以在粪肠球菌,大肠杆菌(malK和afuC),枯草芽孢杆菌(glnO),流感嗜血杆菌(yebM和potA),酿脓链球菌,肺炎链球菌,和鼠伤寒沙门氏菌(Salmonella typhimurium)(malK)中鉴定GBS pho2-2基因产物的同源物。粪肠球菌,酿脓链球菌和肺炎链球菌同源物是从基因组序列数据中鉴定的,且关于基因或基因产物的鉴定,没有注释是可利用的。在所有其它的情况中,同源物代表了ATP-结合转运蛋白,其是ABC型转运蛋白的一部分。ABC型转运蛋白的许多成分是结合于膜或细胞表面,这些***参与在大分子从细胞外环境向细胞内隔室的转运。
实施例8
选择又一个包括称为pho3-14质粒的克隆。此质粒包括互补无前导序列phoA的基因(或其一部分)。基因的核苷酸和推定的氨基酸序列分别作为SEQ ID NOS.16和17列出。
进行pho3-14的氨基酸序列比较。且没有同源物能够在任何公开数据库中被鉴定。GBSpho3-14基因产物的一个同源物可以在酿脓链球菌中鉴定,但是这个同源物是从基因组序列数据中鉴定的,且关于基因或基因产物的鉴定,没有注释是可利用的。使用此酿脓链球菌同源物来检索公开的数据库,没有得到更多的信息。既然pho3-14产品互补了无前导序列phoA基因,可以推断此蛋白质(或其一部分)将最可能位于细胞外。
实施例9
选择又一个包括称为pho3-17质粒的克隆。此质粒包括互补无前导序列phoA的基因(或其一部分)。基因的核苷酸和推定氨基酸序列分别作为SEQ ID NOS.18和19列出。
进行pho3-17的氨基酸序列比较。
可以在变异链球菌和乳酸乳球菌中鉴定GBS Pho3-17基因产物的同源物,具有与N-乙酰基胞壁质酶的相似性。也注意到与未鉴定的基因即源自枯草芽孢杆菌的yubE的相似性。
N-乙酰基胞壁质酶是一种参与细胞***中的自溶素。使用这种有限的信息连同pho3-17互补无前导序列phoA基因的事实,可以推断出pho3-17产物将最可能位于细胞外。
实施例10
选择又一个包括称为pho3-18质粒的克隆。此质粒包括互补无前导序列phoA的基因(或其一部分)。基因的核苷酸和推定氨基酸序列分别作为SEQ ID NOS.20和21列出。
进行pho3-18的氨基酸序列比较。
可以在酿脓链球菌和肺炎链球菌中鉴定GBS Pho3-18基因产物的同源物。这些同源物是从基因组序列数据中鉴定的,且关于基因或基因产物的鉴定,没有注释是可利用的。使用这些酿脓链球菌和肺炎链球菌同源物检索公开的数据库,其表现出某些与外表面和跨越膜蛋白的相似性。既然ORF3-18产物互补了无前导序列phoA基因,可以推断出此蛋白质(或其一部分)将最可能位于细胞外。
实施例11
选择又一个包括称为pho3-1质粒的克隆。此质粒包括互补无前导序列phoA的基因(或其一部分)。基因的核苷酸和推定氨基酸序列分别作为SEQ ID NOS.22和23列出。
进行pho3-1的氨基酸序列比较。
可以在酿脓链球菌,肺炎链球菌,枯草芽孢杆菌(yutD)和粪肠球菌中鉴定GBS Pho3-1基因产物的同源物。酿脓链球菌,肺炎链球菌和粪肠球菌同源物是从基因组序列数据中鉴定的,且关于基因或基因产物的鉴定,没有注释是可利用的。在枯草芽孢杆菌中,yutD基因产物的功能是未知的。然而可以注意到,yutD基因位于枯草芽孢杆菌染色体中含有参与细胞壁合成的基因的区域中。此DNA序列互补了无前导序列的phoA基因的事实暗示此基因产物位于细胞外。
实施例12
选择又一个包括称为pho3-21质粒的克隆。此质粒包括互补无前导序列phoA的基因(或其一部分)。基因的核苷酸和推定氨基酸序列分别作为SEQ ID NOS.24和25列出。
进行pho3-21的氨基酸序列比较。
可以在酿脓链球菌,肺炎链球菌,发酵乳杆菌(Lactobacillus fermentum)(bspA)和路氏乳杆菌(Lactobacillus reuteri)(cnb)中鉴定GBS Pho3-21基因产物的同源物。酿脓链球菌,肺炎链球菌同源物是从基因组序列数据中鉴定的,且关于基因或基因产物的鉴定,没有注释是可利用的。在发酵乳杆菌中,bspA基因产物已经被鉴定为基本(basic)细胞表面-定位的蛋白质,其具有某些与细菌溶质-结合蛋白质第III家族相似的序列(Turner,M.S.等人.1997.细菌学杂志.179:3310-3316)。在路氏乳杆菌中,cnb基因产物已经被鉴定为胶原结合蛋白,其具有某些与细菌ABC转运蛋白溶质结合组分相似的序列(Roos,S.等人.1996.FEMS Microbiol.Lett.144:33-38)。
实施例13
选择又一个包括称为pho3-22质粒的克隆。此质粒包括互补无前导序列phoA的基因(或其一部分)。基因的核苷酸和推定氨基酸序列分别作为SEQ ID NOS.26和27列出。
进行pho3-22的氨基酸序列比较。
可以在粪肠球菌,似马链球菌(Streoticiccys eqyusunukus)(lppC),荧光假单胞菌(Pseudomonas fluorescens)(oprI)和嗜热链球菌(orf142)中鉴定GBS Pho3-22基因产物的同源物。粪肠球菌同源物是从基因组序列数据中鉴定的,且关于基因或基因产物的鉴定,没有注释是可利用的。在似马链球菌中,lppC基因产物已经被鉴定为脂蛋白,其与源自流感嗜血杆菌的E(P4)外膜蛋白质同源(Gase,K.等人1997医学微生物免疫学(Med.Microbiol.Immunol).186:63-73)。同样地,荧光假单胞菌oprI基因编码一重要的外膜脂蛋白(Cornelis,P.等人.1989.分子微生物学3:421-428)。在嗜热链球菌中,orf142产物已经推定地被鉴定为暴露于细胞表面的脂蛋白,其充当噬菌体TP-J34和Sfi21的受体(Neve,H.等人.1998.病毒学(Virology)241:61-72)。ORF3-22产品显示出了与上面同源物较好的相似性,特别是在N-端。这很可能是无前导序列的phoA基因之互补所需要的区域,并因此作为前导序列。
实施例14
选择又一个包括称为pho3-23质粒的克隆。此质粒包括互补无前导序列phoA的基因(或其一部分)。基因的核苷酸和推定氨基酸序列分别作为SEQ ID NOS.28和29列出。
进行pho3-23的氨基酸序列对照。
可以在酿脓链球菌,肺炎链球菌,粪肠球菌和变异链球菌(perM)中鉴定GBS pho3-23基因产物的同源物。酿脓链球菌,肺炎链球菌和粪肠球菌同源物是从基因组序列数据中鉴定的,且关于基因或基因产物的鉴定,没有注释是可利用的。在变异链球菌中,perM基因产物已经被假定地鉴定为通透酶,但是关于此蛋白质的功能没有其它信息是可利用的。考虑到pho3-23编码区域互补无前导序列phoA基因,可以推断pho3-17基因产物将最可能位于细胞外。
实施例15
选择又一个包括称为pho3-24质粒的克隆。此质粒包括互补无前导序列phoA的基因(或其一部分)。基因的核苷酸和推定氨基酸序列分别作为SEQ ID NOS.30和31列出。
进行pho3-24的氨基酸序列比较。
可以在变异链球菌(dltB),肺炎链球菌,酿脓链球菌,粪肠球菌,干酪乳杆菌(Lactobaillus casei)(dltB)和枯草芽孢杆菌(dltB)中鉴定GBS pho3-24基因产物的同源物。肺炎链球菌,酿脓链球菌和粪肠球菌同源物是从基因组序列数据中鉴定的,且关于基因或基因产物的鉴定,没有注释是可利用的。在变异链球菌,干酪乳杆菌和枯草芽孢杆菌中,dltB基因产物已经被鉴定为基本膜蛋白,其参与穿过细胞膜的活性D-丙氨酸的转运中。dltB基因产物参与D-丙氨酰-脂磷壁酸质的生物合成(Heaton,M.P.和F.C.Neuhaus.1992.细菌学杂志174:4707-4717)。在干酪乳杆菌和枯草芽孢杆菌中,认为dltB基因产物包含至少9个膜跨越结构域,显示蛋白质或其一部分暴露于细胞的外面。
实施例16
选择又一个包含称为pho3-29质粒的克隆。此质粒包括互补无前导序列phoA的基因(或其一部分)。基因的核苷酸和推定氨基酸序列分别作为SEQ ID NOS.32和33列出。
进行pho3-29的氨基酸序列比较。
可以布氏疏螺旋体(Borrelia burgdorferi)(p23或ospC),短芽孢杆菌(Bacillus brevis)(owp)和绿脓假单胞菌(Pseudomonas aeruginosa)(oprI)中鉴定GBS pho3-29基因产物的同源物。虽然这些同源物彼此并不相关,它们全部代表重要的外表面蛋白。在布氏疏螺旋体中,ospC基因产物已经被鉴定为23-kDa蛋白,它是这种细菌表面上的免疫显性抗原(Padula,S.J.等人.1993感染与免疫(Infect.Immun).61:5097-5105)。源自短芽孢杆菌的owp基因产物是包括在表面层晶格中的两种主要细胞壁蛋白中的一种(Tsuboi,A.1988.细菌学杂志170:935-945)。最后,源自绿脓假单胞菌的oprI基因编码重要的外膜脂蛋白前体(Saint-Onge,A.等人1992普通微生物学杂志(J.Gen.Microbiol).138:733-741)。
实施例17
选择又一个包含称为pho3-50质粒的克隆。此质粒包括互补无前导序列phoA的基因(或其一部分)。基因的核苷酸和推定氨基酸序列分别作为SEQ ID NOS.34和35列出。
进行pho3-50的氨基酸序列比较。
可以在链球菌(penA,pbp2B,pbpB2),布氏疏螺旋体(pbp2),粪肠球菌(pbpC),金黄色葡萄球菌(Stephylococcus aureus)(pbpA),麻风分枝杆菌(Mycobacterium leprae)(pbpC)和幽门螺杆菌(pbp2)中鉴定GBS Pho3-50基因产物的同源物。在所有的情况中,上面的同源物可以被鉴定为青霉素结合蛋白(PBP)。编码青霉素结合蛋白的基因通常位于与细胞壁合成相关的一簇基因中(Pucci,M.J.等人.1997.细菌学杂志179:5632-5635)。此外,PBP到细菌的细胞壁中,某些或全部蛋白质暴露于外部细菌表面的一般整合。
序列表
<110>Microscience Limited
<120>基因和蛋白质,及其用途
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atg atc cca gta gta atc gaa caa aca agt cgt ggt gaa cgt tct tat 48
Met Ile Pro Val Val Ile Glu Gln Thr Ser Arg Gly Glu Arg Ser Tyr
1 5 10 15
gat att tac tca cgt ctt tta aaa gat cgt att att atg ttg aca ggc 96
Asp Ile Tyr Ser Arg Leu Leu Lys Asp Arg Ile Ile Met Leu Thr Gly
20 25 30
caa gtt gag gat aat atg gcc aat agt atc att gca cag tta ttg ttt 144
Gln Val Glu Asp Asn Met Ala Asn Ser Ile Ile Ala Gln Leu Leu Phe
35 40 45
ctc gat gca caa gat aat aca aag gat att tac ctt tat gtc aat aca 192
Leu Asp Ala Gln Asp Asn Thr Lys Asp Ile Tyr Leu Tyr Val Asn Thr
50 55 60
cca ggt ggt tca gta tcg gct gga ctt gct att gtg gac acc atg aac 240
Pro Gly Gly Ser Val Ser Ala Gly Leu Ala Ile Val Asp Thr Met Asn
65 70 75 80
ttc att aaa tcg gac gta cag acg att gtt atg ggg atg gct gct tcg 288
Phe Ile Lys Ser Asp Val Gln Thr Ile Val Met Gly Met Ala Ala Ser
85 90 95
atg gga acc att att gct tca agt ggt gct aaa gga aaa cgt ttt atg 336
Met Gly Thr Ile Ile Ala Ser Ser Gly Ala Lys Gly Lys Arg Phe Met
100 105 110
tta ccg aat gca gaa tat atg atc cac caa cca atg ggc gga aca ggc 384
Leu Pro Asn Ala Glu Tyr Met Ile His Gln Pro Met Gly Gly Thr Gly
115 120 125
gga ggt aca cag caa tct gat atg gct atc gct gct gag cat ctt tta 432
Gly Gly Thr Gln Gln Ser Asp Met Ala Ile Ala Ala Glu His Leu Leu
130 135 140
aaa acg cgt cat act tta gaa aaa atc tta gct gat aat tct ggt caa 480
Lys Thr Arg His Thr Leu Glu Lys Ile Leu Ala Asp Asn Ser Gly Gln
145 150 155 160
tct att gaa aaa gtc cat gat gat gca gag cgt gat cgt tgg atg agt 528
Ser Ile Glu Lys Val His Asp Asp Ala Glu Arg Asp Arg Trp Met Ser
165 170 175
gct caa gaa aca ctt gat tat ggc ttt att gat gaa atc atg gct aat 576
Ala Gln Glu Thr Leu Asp Tyr Gly Phe Ile Asp Glu Ile Met Ala Asn
180 185 190
aat gaa taagg 587
Asn Glu
<210>2
<211>194
<212>PRT
<213>B群链球菌
<400>2
Met Ile Pro Val Val Ile Glu Gln Thr Ser Arg Gly Glu Arg Ser Tyr
1 5 10 15
Asp Ile Tyr Ser Arg Leu Leu Lys Asp Arg Ile Ile Met Leu Thr Gly
20 25 30
Gln Val Glu Asp Asn Met Ala Asn Ser Ile Ile Ala Gln Leu Leu Phe
35 40 45
Leu Asp Ala Gln Asp Asn Thr Lys Asp Ile Tyr Leu Tyr Val Asn Thr
50 55 60
Pro Gly Gly Ser Val Ser Ala Gly Leu Ala Ile Val Asp Thr Met Asn
65 70 75 80
Phe Ile Lys Ser Asp Val Gln Thr Ile Val Met Gly Met Ala Ala Ser
85 90 95
Met Gly Thr Ile Ile Ala Ser Ser Gly Ala Lys Gly Lys Arg Phe Met
100 105 110
Leu Pro Asn Ala Glu Tyr Met Ile His Gln Pro Met Gly Gly Thr Gly
115 120 125
Gly Gly Thr Gln Gln Ser Asp Met Ala Ile Ala Ala Glu His Leu Leu
130 135 140
Lys Thr Arg His Thr Leu Glu Lys Ile Leu Ala Asp Asn Ser Gly Gln
145 150 155 160
Ser Ile Glu Lys Val His Asp Asp Ala Glu Arg Asp Arg Trp Met Ser
165 170 175
Ala Gln Glu Thr Leu Asp Tyr Gly Phe Ile Asp Glu Ile Met Ala Asn
180 185 190
Asn Glu
<210>3
<211>218
<212>DNA
<213>B群链球菌
<220>
<221>CDS
<222>(1)..(216)
<400>3
atc aga gca tat tct ggt cct ctt tcg gtt ttc ctg cca cgt ttt aaa 48
Ile Arg Ala Tyr Ser Gly Pro Leu Ser Val Phe Leu Pro Arg Phe Lys
1 5 10 15
gct tgt gat ata ata gtc aat gtg agg agg act atc atg tta ttt aag 96
Ala Cys Asp Ile Ile Val Asn Val Arg Arg Thr Ile Met Leu Phe Lys
20 25 30
gaa aaa att cct gga cta ata tta tgc ttt att att gct ata cca tct 144
Glu Lys Ile Pro Gly Leu Ile Leu Cys Phe Ile Ile Ala Ile Pro Ser
35 40 45
tgg ttg ctt ggg ctt tat ctc cct tta ata gga gca cca gtc ttt gct 192
Trp Leu Leu Gly Leu Tyr Leu Pro Leu Ile Gly Ala Pro Val Phe Ala
50 55 60
atc ttg att gga ata att gtt gga tc 218
Ile Leu Ile Gly Ile Ile Val Gly
65 70
<210>4
<211>72
<212>PRT
<213>B群链球菌
<400>4
Ile Arg Ala Tyr Ser Gly Pro Leu Ser Val Phe Leu Pro Arg Phe Lys
1 5 10 15
Ala Cys Asp Ile Ile Val Asn Val Arg Arg Thr Ile Met Leu Phe Lys
20 25 30
Glu Lys Ile Pro Gly Leu Ile Leu Cys Phe Ile Ile Ala Ile Pro Ser
35 40 45
Trp Leu Leu Gly Leu Tyr Leu Pro Leu Ile Gly Ala Pro Val Phe Ala
50 55 60
Ile Leu Ile Gly Ile Ile Val Gly
65 70
<210>5
<211>705
<212>DNA
<213>B群链球菌
<220>
<221>CDS
<222>(1)..(705)
<400>5
atg aat aaa aga aga aaa tta tca aaa ttg aat gta aaa aar caa cat 48
Met Asn Lys Arg Arg Lys Leu Ser Lys Leu Asn Val Lys Lys Gln His
1 5 10 15
tta gct tat gga gct atc act tta gta gcc ctt ttt tca tgt att ttg 96
Leu Ala Tyr Gly Ala Ile Thr Leu Val Ala Leu Phe Ser Cys Ile Leu
20 25 30
gct gta acg gtc atc ttt aaa agt tca caa gtt act act gaa tct ttg 144
Ala Val Thr Val Ile Phe Lys Ser Ser Gln Val Thr Thr Glu Ser Leu
35 40 45
tca aaa gca gat aaa gtt cgc gta gcc aaa aaa tca aaa atg act aag 192
Ser Lys Ala Asp Lys Val Arg Val Ala Lys Lys Ser Lys Met Thr Lys
50 55 60
gcg aca tct aaa tca aaa gta gaa gat gta aaa cag gct cca aaa cct 240
Ala Thr Ser Lys Ser Lys Val Glu Asp Val Lys Gln Ala Pro Lys Pro
65 70 75 80
tct cag gca tct aat gaa gcc cca aaa tca agt tct caa tct aca gaa 288
Ser Gln Ala Ser Asn Glu Ala Pro Lys Ser Ser Ser Gln Ser Thr Glu
85 90 95
gct aat tct cag caa caa gtt act gcg agt gaa gag acg gct gta gaa 336
Ala Asn Ser Gln Gln Gln Val Thr Ala Ser Glu Glu Thr Ala Val Glu
100 105 110
caa gca gtt gta aca gaa ata ccc ctg cta cca gtc agg cac aac aac 384
Gln Ala Val Val Thr Glu Ile Pro Leu Leu Pro Val Arg His Asn Asn
115 120 125
ctt tat gct gtt act gag aca cct tac aac cct gct caa cca cca gac 432
Leu Tyr Ala Val Thr Glu Thr Pro Tyr Asn Pro Ala Gln Pro Pro Asp
130 135 140
caa gtg gcc agg tat gag caa tgg aaa tac tgc cag gcg gtc gga tct 480
Gln Val Ala Arg Tyr Glu Gln Trp Lys Tyr Cys Gln Ala Val Gly Ser
145 150 155 160
gct gct gca gca caa atg gct gct gca aca gga gtc cct cag tct act 528
Ala Ala Ala Ala Gln Met Ala Ala Ala Thr Gly Val Pro Gln Ser Thr
165 170 175
tgg gaa cat att att gcc cgt gaa tca aat ggt aat cct aat gtt gct 576
Trp Glu His Ile Ile Ala Arg Glu Ser Asn Gly Asn Pro Asn Val Ala
180 185 190
aat gcc tca gga gct tca gga ctt ttc caa acg atg cca ggt tgg ggt 624
Asn Ala Ser Gly Ala Ser Gly Leu Phe Gln Thr Met Pro Gly Trp Gly
195 200 205
tca aca gct aca gtt cag gat caa gta att cag cta tta aag ctt att 672
Ser Thr Ala Thr Val Gln Asp Gln Val Ile Gln Leu Leu Lys Leu Ile
210 215 220
cgt gct caa ggg tta tca gct ggg tac cag tga 705
Arg Ala Gln Gly Leu Ser Ala Gly Tyr Gln
225 230 235
<210>6
<211>234
<212>PRT
<213>B群链球菌
<400>6
Met Asn Lys Arg Arg Lys Leu Ser Lys Leu Asn Val Lys Lys Gln His
1 5 10 15
Leu Ala Tyr Gly Ala Ile Thr Leu Val Ala Leu Phe Ser Cys Ile Leu
20 25 30
Ala Val Thr Val Ile Phe Lys Ser Ser Gln Val Thr Thr Glu Ser Leu
35 40 45
Ser Lys Ala Asp Lys Val Arg Val Ala Lys Lys Ser Lys Met Thr Lys
50 55 60
Ala Thr Ser Lys Ser Lys Val Glu Asp Val Lys Gln Ala Pro Lys Pro
65 70 75 80
Ser Gln Ala Ser Asn Glu Ala Pro Lys Ser Ser Ser Gln Ser Thr Glu
85 90 95
Ala Asn Ser Gln Gln Gln Val Thr Ala Ser Glu Glu Thr Ala Val Glu
100 105 110
Gln Ala Val Val Thr Glu Ile Pro Leu Leu Pro Val Arg His Asn Asn
115 120 125
Leu Tyr Ala Val Thr Glu Thr Pro Tyr Asn Pro Ala Gln Pro Pro Asp
130 135 140
Gln Val Ala Arg Tyr Glu Gln Trp Lys Tyr Cys Gln Ala Val Gly Ser
145 150 155 160
Ala Ala Ala Ala Gln Met Ala Ala Ala Thr Gly Val Pro Gln Ser Thr
165 170 175
Trp Glu His Ile Ile Ala Arg Glu Ser Asn Gly Asn Pro Asn Val Ala
180 185 190
Asn Ala Ser Gly Ala Ser Gly Leu Phe Gln Thr Met Pro Gly Trp Gly
195 200 205
Ser Thr Ala Thr Val Gln Asp Gln Val Ile Gln Leu Leu Lys Leu Ile
210 215 220
Arg Ala Gln Gly Leu Ser Ala Gly Tyr Gln
225 230
<210>7
<211>594
<212>DNA
<213>B群链球菌
<220>
<221>CDS
<222>(1)..(594)
<400>7
atg act gaa cca ttt ttt gat aaa gaa tta act tgt cgc cca att gaa 48
Met Thr Glu Pro Phe Phe Asp Lys Glu Leu Thr Cys Arg Pro Ile Glu
1 5 10 15
gcc att cct gaa ttg ttg gaa ttc gat att acc gtt cgt gga gac aac 96
Ala Ile Pro Glu Leu Leu Glu Phe Asp Ile Thr Val Arg Gly Asp Asn
20 25 30
cgt gga tgg ttc aaa gag aac ttt caa aaa gaa aaa atg ata ccg ctt 144
Arg Gly Trp Phe Lys Glu Asn Phe Gln Lys Glu Lys Met Ile Pro Leu
35 40 45
ggt ttc cca gaa agc ttc ttt gag gca gac aaa cta caa aat aat att 192
Gly Phe Pro Glu Ser Phe Phe Glu Ala Asp Lys Leu Gln Asn Asn Ile
50 55 60
tcg ttt aca aaa aaa aat act ttg cga ggt ctc cat gca gag cct tgg 240
Ser Phe Thr Lys Lys Asn Thr Leu Arg Gly Leu His Ala Glu Pro Trp
65 70 75 80
gat aaa tat gtt tcg atc gct gat gaa gga cgt gtg atc ggt act tgg 288
Asp Lys Tyr Val Ser Ile Ala Asp Glu Gly Arg Val Ile Gly Thr Trp
85 90 95
gtt gac ctc cgt gaa ggt gac agt ttt ggt aac gtt tac caa acg att 336
Val Asp Leu Arg Glu Gly Asp Ser Phe Gly Asn Val Tyr Gln Thr Ile
100 105 110
atc gat gcc tca aaa ggt att ttt gtt cca cgc ggc gtt gct aat ggt 384
Ile Asp Ala Ser Lys Gly Ile Phe Val Pro Arg Gly Val Ala Asn Gly
115 120 125
ttc caa gtt ctt tca gat aaa gca gct tat act tat ctc gtt aac gat 432
Phe Gln Val Leu Ser Asp Lys Ala Ala Tyr Thr Tyr Leu Val Asn Asp
130 135 140
tat tgg gca ctt gaa ctc aaa cca aaa tat gct ttc gtt aac tat gca 480
Tyr Trp Ala Leu Glu Leu Lys Pro Lys Tyr Ala Phe Val Asn Tyr Ala
145 150 155 160
gat cca aat cta ggc att cag tgg gaa aat ctw gaa gaa gca gaa gtc 528
Asp Pro Asn Leu Gly Ile Gln Trp Glu Asn Xaa Glu Glu Ala Glu Val
165 170 175
tca gaa gca gat aag aat cac cca ctt ctc aaa gat gta aaa cct ttg 576
Ser Glu Ala Asp Lys Asn His Pro Leu Leu Lys Asp Val Lys Pro Leu
180 185 190
aag aag gaa gat ttg taa 594
Lys Lys Glu Asp Leu
195
<210>8
<211>197
<212>PRT
<213>B群链球菌
<400>8
Met Thr Glu Pro Phe Phe Asp Lys Glu Leu Thr Cys Arg Pro Ile Glu
1 5 10 15
Ala Ile Pro Glu Leu Leu Glu Phe Asp Ile Thr Val Arg Gly Asp Asn
20 25 30
Arg Gly Trp Phe Lys Glu Asn Phe Gln Lys Glu Lys Met Ile Pro Leu
35 40 45
Gly Phe Pro Glu Ser Phe Phe Glu Ala Asp Lys Leu Gln Asn Asn Ile
50 55 60
Ser Phe Thr Lys Lys Asn Thr Leu Arg Gly Leu His Ala Glu Pro Trp
65 70 75 80
Asp Lys Tyr Val Ser Ile Ala Asp Glu Gly Arg Val Ile Gly Thr Trp
85 90 95
Val Asp Leu Arg Glu Gly Asp Ser Phe Gly Asn Val Tyr Gln Thr Ile
100 105 110
Ile Asp Ala Ser Lys Gly Ile Phe Val Pro Arg Gly Val Ala Asn Gly
115 120 125
Phe Gln Val Leu Ser Asp Lys Ala Ala Tyr Thr Tyr Leu Val Asn Asp
130 135 140
Tyr Trp Ala Leu Glu Leu Lys Pro Lys Tyr Ala Phe Val Asn Tyr Ala
145 150 155 160
Asp Pro Asn Leu Gly Ile Gln Trp Glu Asn Xaa Glu Glu Ala Glu Val
165 170 175
Ser Glu Ala Asp Lys Asn His Pro Leu Leu Lys Asp Val Lys Pro Leu
180 185 190
Lys Lys Glu Asp Leu
195
<210>9
<211>1217
<212>DNA
<213>B群链球菌
<220>
<221>CDS
<222>(1)..(570)
<220>
<221>CDS
<222>(679)..(945)
<400>9
tat tat tta atc gga ggg ttg gca gaa atg caa cat gtc aat cat tct 48
Tyr Tyr Leu Ile Gly Gly Leu Ala Glu Met Gln His Val Asn His Ser
1 5 10 15
tct ttt gat aaa gca tca aaa gca gga ttt att att gct tta ggc att 96
Ser Phe Asp Lys Ala Ser Lys Ala Gly Phe Ile Ile Ala Leu Gly Ile
20 25 30
gtt tat gga gat att ggt aca agc cca ctc tat acg atg caa tca ttg 144
Val Tyr Gly Asp Ile Gly Thr Ser Pro Leu Tyr Thr Met Gln Ser Leu
35 40 45
gtt gaa aac caa ggt ggt att tct agt gtc aca gaa tcg ttt atc tta 192
Val Glu Asn Gln Gly Gly Ile Ser Ser Val Thr Glu Ser Phe Ile Leu
50 55 60
ggt tct ata tct tta atc ata tgg acc ttg aca ctt att aca act atc 240
Gly Ser Ile Ser Leu Ile Ile Trp Thr Leu Thr Leu Ile Thr Thr Ile
65 70 75 80
aag tat gtg ctt gta gct tta aag gcg gat aat cac cac gaa ggt ggt 288
Lys Tyr Val Leu Val Ala Leu Lys Ala Asp Asn His His Glu Gly Gly
85 90 95
att ttt tct tta tat acc ctt gtt aga aaa atg aca cct tgg tta att 336
Ile Phe Ser Leu Tyr Thr Leu Val Arg Lys Met Thr Pro Trp Leu Ile
100 105 110
gtt ccg gct gtt att gga ggt gca acc ttg ttg tca gat gga gct ttg 384
Val Pro Ala Val Ile Gly Gly Ala Thr Leu Leu Ser Asp Gly Ala Leu
115 120 125
acg cca gct gta acc gta ctt cag ccg tta agg att aaa gta gtt cct 432
Thr Pro Ala Val Thr Val Leu Gln Pro Leu Arg Ile Lys Val Val Pro
130 135 140
agt ttg cag cat att tcc aga atc aga gta tgt tat ttt gcg acc ttg 480
Ser Leu Gln His Ile Ser Arg Ile Arg Val Cys Tyr Phe Ala Thr Leu
145 150 155 160
tta ttt act gtt act ttt gcc atc caa ggt ttg gaa cgg gtg tta ttg 528
Leu Phe Thr Val Thr Phe Ala Ile Gln Gly Leu Glu Arg Val Leu Leu
165 170 175
gaa tta ttg gcc att atg tta tat ggt ttg cct ttt ggt tta 570
Glu Leu Leu Ala Ile Met Leu Tyr Gly Leu Pro Phe Gly Leu
180 185 190
ncggtctcct tatagttttg cccatccaga agttttcaag cattaatcca tactacggtt 630
tgaaattgtt atttagtcca gagaatcata aaggtatttt tattttag gat cta ttt 687
Asp Leu Phe
tcc tgg cga caa acg gga gca gaa gca cta tac tct gac tta ggt cat 735
Ser Trp Arg Gln Thr Gly Ala Glu Ala Leu Tyr Ser Asp Leu Gly His
195 200 205
gtt ggg cgt gga aat ata cat gtt tca tgg ccg ttc gtt aag gtt gcc 783
Val Gly Arg Gly Asn Ile His Val Ser Trp Pro Phe Val Lys Val Ala
210 215 220 225
att ata ctt tct tat tgt ggg caa ggg gca tgg att tta gct aat aag 831
Ile Ile Leu Ser Tyr Cys Gly Gln Gly Ala Trp Ile Leu Ala Asn Lys
230 235 240
aac gca gga aat gaa ttg aat ccc ttt ttt gct agt att cct tcg caa 879
Asn Ala Gly Asn Glu Leu Asn Pro Phe Phe Ala Ser Ile Pro Ser Gln
245 250 255
ttt aca atg cat gtc gtt att tta gct act ttg gca gct atc atc gct 927
Phe Thr Met His Val Val Ile Leu Ala Thr Leu Ala Ala Ile Ile Ala
260 265 270
tca cag gca ctg att tct ggatcaattt accttaagtt ctgagctatg 975
Ser Gln Ala Leu Ile Ser
275
cgactaaaaa tattcccaca atttcgttca acttatcctg ttgacaatat tgggtcaaac 1035
ctacatacct ggtattaatt ggttcttatt tgccattaca acctctattg gtttgctttt 1095
taagacttca gcgcacatgg aagcagcata tggattagcg ataacaatta cgatgctaat 1155
gacaactatt ttactgtctt tctttttaat tcaaaaagga gtaaagagag gttttagcta 1215
tt 1217
<210>10
<211>190
<212>PRT
<213>B群链球菌
<400>10
Tyr Tyr Leu Ile Gly Gly Leu Ala Glu Met Gln His Val Asn His Ser
1 5 10 15
Ser Phe Asp Lys Ala Ser Lys Ala Gly Phe Ile Ile Ala Leu Gly Ile
20 25 30
Val Tyr Gly Asp Ile Gly Thr Ser Pro Leu Tyr Thr Met Gln Ser Leu
35 40 45
Val Glu Asn Gln Gly Gly Ile Ser Ser Val Thr Glu Ser Phe Ile Leu
50 55 60
Gly Ser Ile Ser Leu Ile Ile Trp Thr Leu Thr Leu Ile Thr Thr Ile
65 70 75 80
Lys Tyr Val Leu Val Ala Leu Lys Ala Asp Asn His His Glu Gly Gly
85 90 95
Ile Phe Ser Leu Tyr Thr Leu Val Arg Lys Met Thr Pro Trp Leu Ile
100 105 110
Val Pro Ala Val Ile Gly Gly Ala Thr Leu Leu Ser Asp Gly Ala Leu
115 120 125
Thr Pro Ala Val Thr Val Leu Gln Pro Leu Arg Ile Lys Val Val Pro
130 135 140
Ser Leu Gln His Ile Ser Arg Ile Arg Val Cys Tyr Phe Ala Thr Leu
145 150 155 160
Leu Phe Thr Val Thr Phe Ala Ile Gln Gly Leu Glu Arg Val Leu Leu
165 170 175
Glu Leu Leu Ala Ile Met Leu Tyr Gly Leu Pro Phe Gly Leu
180 185 190
<210>11
<211>89
<212>PRT
<213>B群链球菌
<400>11
Asp Leu Phe Ser Trp Arg Gln Thr Gly Ala Glu Ala Leu Tyr Ser Asp
1 5 10 15
Leu Gly His Val Gly Arg Gly Asn Ile His Val Ser Trp Pro Phe Val
20 25 30
Lys Val Ala Ile Ile Leu Ser Tyr Cys Gly Gln Gly Ala Trp Ile Leu
35 40 45
Ala Asn Lys Asn Ala Gly Asn Glu Leu Asn Pro Phe Phe Ala Ser Ile
50 55 60
Pro Ser Gln Phe Thr Met His Val Val Ile Leu Ala Thr Leu Ala Ala
65 70 75 80
Ile Ile Ala Ser Gln Ala Leu Ile Ser
85
<210>12
<211>378
<212>DNA
<213>B群链球菌
<220>
<221>CDS
<222>(1)..(378)
<400>12
atg cag gta ttt tta aat att gtc aat aaa ttc ttt gat cca gtt att 48
Met Gln Val Phe Leu Asn Ile Val Asn Lys Phe Phe Asp Pro Val Ile
1 5 10 15
cat atg ggt tcg gga gtt gtg atg cta att gtc atg aca ggt tta gcc 96
His Met Gly Ser Gly Val Val Met Leu Ile Val Met Thr Gly Leu Ala
20 25 30
atg ata ttt gga gtg aag ttt tct aaa gca ctt gaa ggt ggt att aag 144
Met Ile Phe Gly Val Lys Phe Ser Lys Ala Leu Glu Gly Gly Ile Lys
35 40 45
tta gct att gct ctt acg ggt att ggt gct att att ggt att tta act 192
Leu Ala Ile Ala Leu Thr Gly Ile Gly Ala Ile Ile Gly Ile Leu Thr
50 55 60
ggt gct ttt tcc gaa tca ctt caa gct ttt gtt aaa aat aca gga atc 240
Gly Ala Phe Ser Glu Ser Leu Gln Ala Phe Val Lys Asn Thr Gly Ile
65 70 75 80
aat cta agc att att gac gtt ggt tgg gct cca tta gca act att aca 288
Asn Leu Ser Ile Ile Asp Val Gly Trp Ala Pro Leu Ala Thr Ile Thr
85 90 95
tgg gga tca cca tat acg ctt tac ttc tta tta atc atg ctt att gtc 336
Trp Gly Ser Pro Tyr Thr Leu Tyr Phe Leu Leu Ile Met Leu Ile Val
100 105 110
aat att gtt atg att gtt atg aaa aaa aaa cgg ata cct tag 378
Asn Ile Val Met Ile Val Met Lys Lys Lys Arg Ile Pro
115 120 125
<210>13
<211>125
<212>PRT
<213>B群链球菌
<400>13
Met Gln Val Phe Leu Asn Ile Val Asn Lys Phe Phe Asp Pro Val Ile
1 5 10 15
His Met Gly Ser Gly Val Val Met Leu Ile Val Met Thr Gly Leu Ala
20 25 30
Met Ile Phe Gly Val Lys Phe Ser Lys Ala Leu Glu Gly Gly Ile Lys
35 40 45
Leu Ala Ile Ala Leu Thr Gly Ile Gly Ala Ile Ile Gly Ile Leu Thr
50 55 60
Gly Ala Phe Ser Glu Ser Leu Gln Ala Phe Val Lys Asn Thr Gly Ile
65 70 75 80
Asn Leu Ser Ile Ile Asp Val Gly Trp Ala Pro Leu Ala Thr Ile Thr
85 90 95
Trp Gly Ser Pro Tyr Thr Leu Tyr Phe Leu Leu Ile Met Leu Ile Val
100 105 110
Asn Ile Val Met Ile Val Met Lys Lys Lys Arg Ile Pro
115 120 125
<210>14
<211>705
<212>DMA
<213>B群链球菌
<220>
<221>CDS
<222>(118)..(705)
<400>14
ggatcgggcg caagcttaac gattcttttt aaaatcatta aattttaaaa caaatttcag 60
acatattgcc aaagttttga tattattact ataatatagt ttgtagagga gaataat 117
atg ggc caa gaa cct atc atc gaa tat caa aat atc aat aaa gtg tat 165
Met Gly Gln Glu Pro Ile Ile Glu Tyr Gln Asn Ile Asn Lys Val Tyr
1 5 10 15
ggg gaa aat gtt gcg gtt gaa gat att aac ctt aaa att tac cct ggt 213
Gly Glu Asn Val Ala Val Glu Asp Ile Asn Leu Lys Ile Tyr Pro Gly
20 25 30
gat ttc gtt tgt ttc atc ggt acg agt gga tca ggt aaa aca aca tta 261
Asp Phe Val Cys Phe Ile Gly Thr Ser Gly Ser Gly Lys Thr Thr Leu
35 40 45
atg cgt atg gtt aac cat atg tta aaa cca aca aat ggt act cta tta 309
Met Arg Met Val Asn His Met Leu Lys Pro Thr Asn Gly Thr Leu Leu
50 55 60
ttt aag gga aaa gat atc tct act att aac ccc att gaa tta aga cgc 357
Phe Lys Gly Lys Asp Ile Ser Thr Ile Asn Pro Ile Glu Leu Arg Arg
65 70 75 80
aga att gga tat gtt atc caa aac att ggt tta atg cct cat atg acc 405
Arg Ile Gly Tyr Val Ile Gln Asn Ile Gly Leu Met Pro His Met Thr
85 90 95
att tac gaa aat ata gtt ctt gta cca aaa tta ttg aaa tgg tca gaa 453
Ile Tyr Glu Asn Ile Val Leu Val Pro Lys Leu Leu Lys Trp Ser Glu
100 105 110
gaa gct aaa aga gct aaa gca agg gaa ctt att aaa tta gtt gaa tta 501
Glu Ala Lys Arg Ala Lys Ala Arg Glu Leu Ile Lys Leu Val Glu Leu
115 120 125
ccc gaa gaa tat ttg gat cgc tac cct agt gag ttg tct ggc ggt cag 549
Pro Glu Glu Tyr Leu Asp Arg Tyr Pro Ser Glu Leu Ser Gly Gly Gln
130 135 140
caa caa cgt atc ggt gtc att cgc gct ctt gca gca gac caa gat att 597
Gln Gln Arg Ile Gly Val Ile Arg Ala Leu Ala Ala Asp Gln Asp Ile
145 150 155 160
att tta atg gat gag cct ttt gga gct ctg gat cct att act aga gaa 645
Ile Leu Met Asp Glu Pro Phe Gly Ala Leu Asp Pro Ile Thr Arg Glu
165 170 175
ggt att caa gac ttt agt caa gtc tct tca gga aga aat ggg gga aaa 693
Gly Ile Gln Asp Phe Ser Gln Val Ser Ser Gly Arg Asn Gly Gly Lys
180 185 190
cta tca tct tag 705
Leu Ser Ser
195
<210>15
<211>195
<212>PRT
<213>B群链球菌
<400>15
Met Gly Gln Glu Pro Ile Ile Glu Tyr Gln Asn Ile Asn Lys Val Tyr
1 5 10 15
Gly Glu Asn Val Ala Val Glu Asp Ile Asn Leu Lys Ile Tyr Pro Gly
20 25 30
Asp Phe Val Cys Phe Ile Gly Thr Ser Gly Ser Gly Lys Thr Thr Leu
35 40 45
Met Arg Met Val Asn His Met Leu Lys Pro Thr Asn Gly Thr Leu Leu
50 55 60
Phe Lys Gly Lys Asp Ile Ser Thr Ile Asn Pro Ile Glu Leu Arg Arg
65 70 75 80
Arg Ile Gly Tyr Val Ile Gln Asn Ile Gly Leu Met Pro His Met Thr
85 90 95
Ile Tyr Glu Asn Ile Val Leu Val Pro Lys Leu Leu Lys Trp Ser Glu
100 105 110
Glu Ala Lys Arg Ala Lys Ala Arg Glu Leu Ile Lys Leu Val Glu Leu
115 120 125
Pro Glu Glu Tyr Leu Asp Arg Tyr Pro Ser Glu Leu Ser Gly Gly Gln
130 135 140
Gln Gln Arg Ile Gly Val Ile Arg Ala Leu Ala Ala Asp Gln Asp Ile
145 150 155 160
Ile Leu Met Asp Glu Pro Phe Gly Ala Leu Asp Pro Ile Thr Arg Glu
165 170 175
Gly Ile Gln Asp Phe Ser Gln Val Ser Ser Gly Arg Asn Gly Gly Lys
180 185 190
Leu Ser Ser
195
<210>16
<211>367
<212>DNA
<213>B群链球菌
<220>
<221>CDS
<222>(1)..(366)
<400>16
atc cct tat agt gat gtt ttt gct aca gga gga ttt tta tac tat gta 48
Ile Pro Tyr Ser Asp Val Phe Ala Thr Gly Gly Phe Leu Tyr Tyr Val
1 5 10 15
acg att gct cta agt tac ctt tta ggg tct agt atc tgg tta ttt att 96
Thr Ile Ala Leu Ser Tyr Leu Leu Gly Ser Ser Ile Trp Leu Phe Ile
20 25 30
gta cag ttt att gct tac tat gta tct gga att tat ttt tat aaa tta 144
Val Gln Phe Ile Ala Tyr Tyr Val Ser Gly Ile Tyr Phe Tyr Lys Leu
35 40 45
gtt tat tat gtg gca caa agt gaa att gtc tcg ata ggc atg acg ttg 192
Val Tyr Tyr Val Ala Gln Ser Glu Ile Val Ser Ile Gly Met Thr Leu
50 55 60
att ttc tat ata atg aat att gtc tta gga ttc ggt ggt atg tac cca 240
Ile Phe Tyr Ile Met Asn Ile Val Leu Gly Phe Gly Gly Met Tyr Pro
65 70 75 80
ata cag tgg gca tta cct ttt atg ctc att tcg cta tgg ttt tta att 288
Ile Gln Trp Ala Leu Pro Phe Met Leu Ile Ser Leu Trp Phe Leu Ile
85 90 95
aaa ttt tgt gtc gat aat atc gtt gat gaa gca ttt ata ttt tat ggt 336
Lys Phe Cys Val Asp Asn Ile Val Asp Glu Ala Phe Ile Phe Tyr Gly
100 105 110
att tta gca gca ttc tca cta ttt ata gat c 367
Ile Leu Ala Ala Phe Ser Leu Phe Ile Asp
115 120
<210>17
<211>122
<212>PRT
<213>B群链球菌
<400>17
Ile Pro Tyr Ser Asp Val Phe Ala Thr Gly Gly Phe Leu Tyr Tyr Val
1 5 10 15
Thr Ile Ala Leu Ser Tyr Leu Leu Gly Ser Ser Ile Trp Leu Phe Ile
20 25 30
Val Gln Phe Ile Ala Tyr Tyr Val Ser Gly Ile Tyr Phe Tyr Lys Leu
35 40 45
Val Tyr Tyr Val Ala Gln Ser Glu Ile Val Ser Ile Gly Met Thr Leu
50 55 60
Ile Phe Tyr Ile Met Asn Ile Val Leu Gly Phe Gly Gly Met Tyr Pro
65 70 75 80
Ile Gln Trp Ala Leu Pro Phe Met Leu Ile Ser Leu Trp Phe Leu Ile
85 90 95
Lys Phe Cys Val Asp Asn Ile Val Asp Glu Ala Phe Ile Phe Tyr Gly
100 105 110
Ile Leu Ala Ala Phe Ser Leu Phe Ile Asp
115 120
<210>18
<211>570
<212>DNA
<213>B群链球菌
<220>
<221>CDS
<222>(1)..(570)
<400>18
atg agg aaa cgt ttt tcc ttg cta aat ttt att gtt gtt act ttt att 48
Met Arg Lys Arg Phe Ser Leu Leu Asn Phe Ile Val Val Thr Phe Ile
1 5 10 15
ttc ttt ttc ttt att ctt ttt ccg ctt tta aac cat aag gga aaa gta 96
Phe Phe Phe Phe Ile Leu Phe Pro Leu Leu Asn His Lys Gly Lys Val
20 25 30
gat gct aat tct agg cag agt gtt acc tac acc aaa gaa gaa ttt ata 144
Asp Ala Asn Ser Arg Gln Ser Val Thr Tyr Thr Lys Glu Glu Phe Ile
35 40 45
caa aaa att gtg cca gat gcg caa gat cta gga aag tcg tac ggt att 192
Gln Lys Ile Val Pro Asp Ala Gln Asp Leu Gly Lys Ser Tyr Gly Ile
50 55 60
cgt cct tca ttt att att gca cag gcg gct ttg gat tct gat ttc gga 240
Arg Pro Ser Phe Ile Ile Ala Gln Ala Ala Leu Asp Ser Asp Phe Gly
65 70 75 80
gag aaa tat agc tat agt atc ata atc tgt tgg ttg ctt gca gaa cca 288
Glu Lys Tyr Ser Tyr Ser Ile Ile Ile Cys Trp Leu Leu Ala Glu Pro
85 90 95
gga acg ccc tca att acc tta aat gat agt agt aca gga aaa aaa cag 336
Gly Thr Pro Ser Ile Thr Leu Asn Asp Ser Ser Thr Gly Lys Lys Gln
100 105 110
gaa aag caa ttt act cat tat aaa tct tgg aag tat tca atg gatgat 384
Glu Lys Gln Phe Thr His Tyr Lys Ser Trp Lys Tyr Ser Met Asp Asp
115 120 125
tac ctt gct cat ata aaa tct gga gcg aca ggc aaa aaa gat tca tat 432
Tyr Leu Ala His Ile Lys Ser Gly Ala Thr Gly Lys Lys Asp Ser Tyr
130 135 140
act ata atg gtg tct gtt aaa aat cca aaa act tta gtg caa aaa tta 480
Thr Ile Met Val Ser Val Lys Asn Pro Lys Thr Leu Val Gln Lys Leu
145 150 155 160
caa gat agt ggt ttt gat aat gac aaa aag tac gct aaa aaa atg acg 528
Gln Asp Ser Gly Phe Asp Asn Asp Lys Lys Tyr Ala Lys Lys Met Thr
165 170 175
gaa atc att gat ttg tat gat tta aca aga tat gat aag tga 570
Glu Ile Ile Asp Leu Tyr Asp Leu Thr Arg Tyr Asp Lys
180 185 190
<210>19
<211>189
<212>PRT
<213>B群链球菌
<400>19
Met Arg Lys Arg Phe Ser Leu Leu Asn Phe Ile Val Val Thr Phe Ile
1 5 10 15
Phe Phe Phe Phe Ile Leu Phe Pro Leu Leu Asn His Lys Gly Lys Val
20 25 30
Asp Ala Asn Ser Arg Gln Ser Val Thr Tyr Thr Lys Glu Glu Phe Ile
35 40 45
Gln Lys Ile Val Pro Asp Ala Gln Asp Leu Gly Lys Ser Tyr Gly Ile
50 55 60
Arg Pro Ser Phe Ile Ile Ala Gln Ala Ala Leu Asp Ser Asp Phe Gly
65 70 75 80
Glu Lys Tyr Ser Tyr Ser Ile Ile Ile Cys Trp Leu Leu Ala Glu Pro
85 90 95
Gly Thr Pro Ser Ile Thr Leu Asn Asp Ser Ser Thr Gly Lys Lys Gln
100 105 110
Glu Lys Gln Phe Thr His Tyr Lys Ser Trp Lys Tyr Ser Met Asp Asp
115 120 125
Tyr Leu Ala His Ile Lys Ser Gly Ala Thr Gly Lys Lys Asp Ser Tyr
130 135 140
Thr Ile Met Val Ser Val Lys Asn Pro Lys Thr Leu Val Gln Lys Leu
145 150 155 160
Gln Asp Ser Gly Phe Asp Asn Asp Lys Lys Tyr Ala Lys Lys Met Thr
165 170 175
Glu Ile Ile Asp Leu Tyr Asp Leu Thr Arg Tyr Asp Lys
180 185
<210>20
<211>978
<212>DNA
<213>B群链球菌
<220>
<221>CDS
<222>(1)..(978)
<400>20
atg ctt gtc atc att ttg atc att gta cta gct agt ctg aca gtg acg 48
Met Leu Val Ile Ile Leu Ile Ile Val Leu Ala Ser Leu Thr Val Thr
1 5 10 15
ata att tct tac cca aaa atg acg gaa tta aca aag tcc gtt gaa aaa 96
Ile Ile Ser Tyr Pro Lys Met Thr Glu Leu Thr Lys Ser Val Glu Lys
20 25 30
caa ctt gaa gat aat gct gat aat cta tca gac caa ctg aca tat cag 144
Gln Leu Glu Asp Asn Ala Asp Asn Leu Ser Asp Gln Leu Thr Tyr Gln
35 40 45
ata gaa gtg gcg caa aaa gat caa atc tac gtg act aat cag cta aac 192
Ile Glu Val Ala Gln Lys Asp Gln Ile Tyr Val Thr Asn Gln Leu Asn
50 55 60
cgt atg caa cag gaa att atc agt cgc tta ccg ata tgc gta cag aat 240
Arg Met Gln Gln Glu Ile Ile Ser Arg Leu Pro Ile Cys Val Gln Asn
65 70 75 80
aaa tca gca tta acg gag agt cga gat cga tca gac aaa cgc ttg gaa 288
Lys Ser Ala Leu Thr Glu Ser Arg Asp Arg Ser Asp Lys Arg Leu Glu
85 90 95
ttg att aac tcc aat tta tct cag tca gtt cag aaa atg caa gat tca 336
Leu Ile Asn Ser Asn Leu Ser Gln Ser Val Gln Lys Met Gln Asp Ser
100 105 110
atg aaa aac gct tgg atc aaa tgc gcc aaa ctg ttg agg aaa agc tgg 384
Met Lys Asn Ala Trp Ile Lys Cys Ala Lys Leu Leu Arg Lys Ser Trp
115 120 125
aaa aaa cgc tac aaa cgc gtt gca aac ttc ttt gaa act gta tcg cgt 432
Lys Lys Arg Tyr Lys Arg Val Ala Asn Phe Phe Glu Thr Val Ser Arg
130 135 140
caa cta gag agc gtc aat caa ggt ctg ggt aga tgg aaa ctg tgc caa 480
Gln Leu Glu Ser Val Asn Gln Gly Leu Gly Arg Trp Lys Leu Cys Gln
145 150 155 160
gat gtt ggt acc act gaa caa agt ctg tca aat act aag aca agg gga 528
Asp Val Gly Thr Thr Glu Gln Ser Leu Ser Asn Thr Lys Thr Arg Gly
165 170 175
ata tta ggg gag tta caa ctc ggt caa att ata gaa gat att atg aca 576
Ile Leu Gly Glu Leu Gln Leu Gly Gln Ile Ile Glu Asp Ile Met Thr
180 185 190
gtt agt caa tat gag aga gaa ttt cct acg gtg tct ggc tct tct gag 624
Val Ser Gln Tyr Glu Arg Glu Phe Pro Thr Val Ser Gly Ser Ser Glu
195 200 205
cgt gtt gaa tat gct att aaa tac ctg gaa atg gtc agg gag att ata 672
Arg Val Glu Tyr Ala Ile Lys Tyr Leu Glu Met Val Arg Glu Ile Ile
210 215 220
tct att tgc cta ttg act cta agt ttc tct aga aga tta tta ccg att 720
Ser Ile Cys Leu Leu Thr Leu Ser Phe Ser Arg Arg Leu Leu Pro Ile
225 230 235 240
ggg aga tgc tta tgg aat tgg gtg acc agg ttc aaa tgg aac tct att 768
Gly Arg Cys Leu Trp Asn Trp Val Thr Arg Phe Lys Trp Asn Ser Ile
245 250 255
cgt aat ctt tac tgg gca agt att cgt aaa ttt gca aaa gat ata aac 816
Arg Asn Leu Tyr Trp Ala Ser Ile Arg Lys Phe Ala Lys Asp Ile Asn
260 265 270
aat aag tac tta aat cct cct gaa acg aca aat ttt ggt atc atg ttc 864
Asn Lys Tyr Leu Asn Pro Pro Glu Thr Thr Asn Phe Gly Ile Met Phe
275 280 285
tta cca act gaa ggg ctc tat tct gaa gtg gta aga aat gca aca ttc 912
Leu Pro Thr Glu Gly Leu Tyr Ser Glu Val Val Arg Asn Ala Thr Phe
290 295 300
ttt gat agt cta aga cgt gac gaa aat att gta gta gct gga ccg tca 960
Phe Asp Ser Leu Arg Arg Asp Glu Asn Ile Val Val Ala Gly Pro Ser
305 310 315 320
acc tta tct gct tac taa 978
Thr Leu Ser Ala Tyr
325
<210>21
<211>325
<212>PRT
<213>B群链球菌
<400>21
Met Leu Val Ile Ile Leu Ile Ile Val Leu Ala Ser Leu Thr Val Thr
1 5 10 15
Ile Ile Ser Tyr Pro Lys Met Thr Glu Leu Thr Lys Ser Val Glu Lys
20 25 30
Gln Leu Glu Asp Asn Ala Asp Asn Leu Ser Asp Gln Leu Thr Tyr Gln
35 40 45
Ile Glu Val Ala Gln Lys Asp Gln Ile Tyr Val Thr Asn Gln Leu Asn
50 55 60
Arg Met Gln Gln Glu Ile Ile Ser Arg Leu Pro Ile Cys Val Gln Asn
65 70 75 80
Lys Ser Ala Leu Thr Glu Ser Arg Asp Arg Ser Asp Lys Arg Leu Glu
85 90 95
Leu Ile Asn Ser Asn Leu Ser Gln Ser Val Gln Lys Met Gln Asp Ser
100 105 110
Met Lys Asn Ala Trp Ile Lys Cys Ala Lys Leu Leu Arg Lys Ser Trp
115 120 125
Lys Lys Arg Tyr Lys Arg Val Ala Asn Phe Phe Glu Thr Val Ser Arg
130 135 140
Gln Leu Glu Ser Val Asn Gln Gly Leu Gly Arg Trp Lys Leu Cys Gln
145 150 155 160
Asp Val Gly Thr Thr Glu Gln Ser Leu Ser Asn Thr Lys Thr Arg Gly
165 170 175
Ile Leu Gly Glu Leu Gln Leu Gly Gln Ile Ile Glu Asp Ile Met Thr
180 185 190
Val Ser Gln Tyr Glu Arg Glu Phe Pro Thr Val Ser Gly Ser Ser Glu
195 200 205
Arg Val Glu Tyr Ala Ile Lys Tyr Leu Glu Met Val Arg Glu Ile Ile
210 215 220
Ser Ile Cys Leu Leu Thr Leu Ser Phe Ser Arg Arg Leu Leu Pro Ile
225 230 235 240
Gly Arg Cys Leu Trp Asn Trp Val Thr Arg Phe Lys Trp Asn Ser Ile
245 250 255
Arg Asn Leu Tyr Trp Ala Ser Ile Arg Lys Phe Ala Lys Asp Ile Asn
260 265 270
Asn Lys Tyr Leu Asn Pro Pro Glu Thr Thr Asn Phe Gly Ile Met Phe
275 280 285
Leu Pro Thr Glu Gly Leu Tyr Ser Glu Val Val Arg Asn Ala Thr Phe
290 295 300
Phe Asp Ser Leu Arg Arg Asp Glu Asn Ile Val Val Ala Gly Pro Ser
305 310 315 320
Thr Leu Ser Ala Tyr
325
<210>22
<211>579
<212>DNA
<213>B群链球菌
<220>
<221>CDS
<222>(1)..(579)
<400>22
atg cga aaa gaa gtg aca cca gag atg ctt aac tat aat aag tat cct 48
Met Arg Lys Glu Val Thr Pro Glu Met Leu Asn Tyr Asn Lys Tyr Pro
1 5 10 15
ggc cca cag ttt att cac ttt gaa aat atc gtt aaa agt gat gat att 96
Gly Pro Gln Phe Ile His Phe Glu Asn Ile Val Lys Ser Asp Asp Ile
20 25 30
gaa ttt caa ctt gtt att aat gaa aaa tca gct ttt gat gtg act gtc 144
Glu Phe Gln Leu Val Ile Asn Glu Lys Ser Ala Phe Asp Val Thr Val
35 40 45
ttt gga caa cgt ttt tct gag att tta tta aaa tat gat ttt atc gtt 192
Phe Gly Gln Arg Phe Ser Glu Ile Leu Leu Lys Tyr Asp Phe Ile Val
50 55 60
ggc gat tgg ggt aac gag cag ttg agg cta aga ggc ttt tac aaa gat 240
Gly Asp Trp Gly Asn Glu Gln Leu Arg Leu Arg Gly Phe Tyr Lys Asp
65 70 75 80
gct agt acg att aga aaa aat agc cgg att tca cgt tta gaa gat tat 288
Ala Ser Thr Ile Arg Lys Asn Ser Arg Ile Ser Arg Leu Glu Asp Tyr
85 90 95
att aaa gag tat tgt aac ttt ggt tgt gct tat ttt gtg ttg gag aat 336
Ile Lys Glu Tyr Cys Asn Phe Gly Cys Ala Tyr Phe Val Leu Glu Asn
100 105 110
cca aat cct aga gat att aaa ttt gat gat gaa aga cct cat aag cgt 384
Pro Asn Pro Arg Asp Ile Lys Phe Asp Asp Glu Arg Pro His Lys Arg
115 120 125
cgt aag tca aga tcc aaa tca caa tca tca aag tca caa act aga aat 432
Arg Lys Ser Arg Ser Lys Ser Gln Ser Ser Lys Ser Gln Thr Arg Asn
130 135 140
aat cgt tcc cag tca aat gcc aat gct cat ttt aca agt aaa aag cgt 480
Asn Arg Ser Gln Ser Asn Ala Asn Ala His Phe Thr Ser Lys Lys Arg
145 150 155 160
aaa gac aca aaa cgc cgt caa gaa cgt cat att aaa gaa gag caa gat 528
Lys Asp Thr Lys Arg Arg Gln Glu Arg His Ile Lys Glu Glu Gln Asp
165 170 175
aag gaa atg acc tct gca aag cag cat ttg tta ttc gta aga aaa aat 576
Lys Glu Met Thr Ser Ala Lys Gln His Leu Leu Phe Val Arg Lys Asn
180 185 190
taa 579
<210>23
<211>192
<212>PRT
<213>B群链球菌
<400>23
Met Arg Lys Glu Val Thr Pro Glu Met Leu Asn Tyr Asn Lys Tyr Pro
1 5 10 15
Gly Pro Gln Phe Ile His Phe Glu Asn Ile Val Lys Ser Asp Asp Ile
20 25 30
Glu Phe Gln Leu Val Ile Asn Glu Lys Ser Ala Phe Asp Val Thr Val
35 40 45
Phe Gly Gln Arg Phe Ser Glu Ile Leu Leu Lys Tyr Asp Phe Ile Val
50 55 60
Gly Asp Trp Gly Asn Glu Gln Leu Arg Leu Arg Gly Phe Tyr Lys Asp
65 70 75 80
Ala Ser Thr Ile Arg Lys Asn Ser Arg Ile Ser Arg Leu Glu Asp Tyr
85 90 95
Ile Lys Glu Tyr Cys Asn Phe Gly Cys Ala Tyr Phe Val Leu Glu Asn
100 105 110
Pro Asn Pro Arg Asp Ile Lys Phe Asp Asp Glu Arg Pro His Lys Arg
115 120 125
Arg Lys Ser Arg Ser Lys Ser Gln Ser Ser Lys Ser Gln Thr Arg Asn
130 135 140
Asn Arg Ser Gln Ser Asn Ala Asn Ala His Phe Thr Ser Lys Lys Arg
145 150 155 160
Lys Asp Thr Lys Arg Arg Gln Glu Arg His Ile Lys Glu Glu Gln Asp
165 170 175
Lys Glu Met Thr Ser Ala Lys Gln His Leu Leu Phe Val Arg Lys Asn
180 185 190
<210>24
<211>609
<212>DNA
<213>B群链球菌
<220>
<221>CDS
<222>(1)..(609)
<400>24
atg aca ata aaa aaa gtg tta agt gta aca gga att att tta gtg aca 48
Met Thr Ile Lys Lys Val Leu Ser Val Thr Gly Ile Ile Leu Val Thr
1 5 10 15
gta gcg tct cta gct gct tgt agc tca aaa tct cat act act aag acg 96
Val Ala Ser Leu Ala Ala Cys Ser Ser Lys Ser His Thr Thr Lys Thr
20 25 30
ggc aaa aaa gaa gtt aat ttt gca act gtt gga aca acg gca cct ttt 144
Gly Lys Lys Glu Val Asn Phe Ala Thr Val Gly Thr Thr Ala Pro Phe
35 40 45
tct tat gtg aag gat ggg aaa ctg act ggc ttt gat att gaa gta gcc 192
Ser Tyr Val Lys Asp Gly Lys Leu Thr Gly Phe Asp Ile Glu Val Ala
50 55 60
aaa gct gtt ttt aaa ggt tca gat aac tat aaa gtc act ttt aaa aaa 240
Lys Ala Val Phe Lys Gly Ser Asp Asn Tyr Lys Val Thr Phe Lys Lys
65 70 75 80
aca gaa tgg tca tcg gta ttt acc ggc att gat tca gga aag ttt caa 288
Thr Glu Trp Ser Ser Val Phe Thr Gly Ile Asp Ser Gly Lys Phe Gln
85 90 95
atg ggt gga aat aat att tct tat tca tca gag aga tct caa aaa tay 336
Met Gly Gly Asn Asn Ile Ser Tyr Ser Ser Glu Arg Ser Gln Lys Tyr
100 105 110
tta ttt tca tac cca ata ggc tct act cct tca gtt tta gca gtt cct 384
Leu Phe Ser Tyr Pro Ile Gly Ser Thr Pro Ser Val Leu Ala Val Pro
115 120 125
aag aat agt aat atc aaa gct tat aat gat att agt ggt cat aaa aca 432
Lys Asn Ser Asn Ile Lys Ala Tyr Asn Asp Ile Ser Gly His Lys Thr
130 135 140
cag gtt gtc caa gga acg aca act gcc aag caa tta gaa aat ttc aat 480
Gln Val Val Gln Gly Thr Thr Thr Ala Lys Gln Leu Glu Asn Phe Asn
145 150 155 160
aaa gag cat cag aaa aat cct gtt act cta aaa tat act aat gaa aat 528
Lys Glu His Gln Lys Asn Pro Val Thr Leu Lys Tyr Thr Asn Glu Asn
165 170 175
att aca cag att cta acg aat ttg agt gat gga aaa gct gat ttt aaa 576
Ile Thr Gln Ile Leu Thr Asn Leu Ser Asp Gly Lys Ala Asp Phe Lys
180 185 190
ctt ttg acg gac caa ctg tta acg cta tta taa 609
Leu Leu Thr Asp Gln Leu Leu Thr Leu Leu
195 200
<210>25
<211>202
<212>PRT
<213>B群链球菌
<400>25
Met Thr Ile Lys Lys Val Leu Ser Val Thr Gly Ile Ile Leu Val Thr
1 5 10 15
Val Ala Ser Leu Ala Ala Cys Ser Ser Lys Ser His Thr Thr Lys Thr
20 25 30
Gly Lys Lys Glu Val Asn Phe Ala Thr Val Gly Thr Thr Ala Pro Phe
35 40 45
Ser Tyr Val Lys Asp Gly Lys Leu Thr Gly Phe Asp Ile Glu Val Ala
50 55 60
Lys Ala Val Phe Lys Gly Ser Asp Asn Tyr Lys Val Thr Phe Lys Lys
65 70 75 80
Thr Glu Trp Ser Ser Val Phe Thr Gly Ile Asp Ser Gly Lys Phe Gln
85 90 95
Met Gly Gly Asn Asn Ile Ser Tyr Ser Ser Glu Arg Ser Gln Lys Tyr
100 105 110
Leu Phe Ser Tyr Pro Ile Gly Ser Thr Pro Ser Val Leu Ala Val Pro
115 120 125
Lys Asn Ser Asn Ile Lys Ala Tyr Asn Asp Ile Ser Gly His Lys Thr
130 135 140
Gln Val Val Gln Gly Thr Thr Thr Ala Lys Gln Leu Glu Asn Phe Asn
145 150 155 160
Lys Glu His Gln Lys Asn Pro Val Thr Leu Lys Tyr Thr Asn Glu Asn
165 170 175
Ile Thr Gln Ile Leu Thr Asn Leu Ser Asp Gly Lys Ala Asp Phe Lys
180 185 190
Leu Leu Thr Asp Gln Leu Leu Thr Leu Leu
195 200
<210>26
<211>357
<212>DNA
<213>B群链球菌
<220>
<221>CDS
<222>(1)..(357)
<400>26
atg aag aat ata aca aag cta tca act gtt gct tta agc cta cta ctt 48
Met Lys Asn Ile Thr Lys Leu Ser Thr Val Ala Leu Ser Leu Leu Leu
1 5 10 15
tgt acg gcg tgt gct gca tca aac acg tct aca tct aaa aca cag tct 96
Cys Thr Ala Cys Ala Ala Ser Asn Thr Ser Thr Ser Lys Thr Gln Ser
20 25 30
cat cat cct aaa caa act aaa ctc aca gat aag caa aaa gaa gaa ccc 144
His His Pro Lys Gln Thr Lys Leu Thr Asp Lys Gln Lys Glu Glu Pro
35 40 45
aaa aac aaa gaa gct gct gat caa gag atg cat ccc caa ggc gct gtt 192
Lys Asn Lys Glu Ala Ala Asp Gln Glu Met His Pro Gln Gly Ala Val
50 55 60
gat ttg aca aaa tat aag gca aaa ccg gtc aaa gat tat gga aaa aaa 240
Asp Leu Thr Lys Tyr Lys Ala Lys Pro Val Lys Asp Tyr Gly Lys Lys
65 70 75 80
atc gat gtt ggt gat ggc aag aaa atg aac att tat gaa act ggt cag 288
Ile Asp Val Gly Asp Gly Lys Lys Met Asn Ile Tyr Glu Thr Gly Gln
85 90 95
gga aaa att cca att gtt ttt att cct ggt caa gct gag att cgc cac 336
Gly Lys Ile Pro Ile Val Phe Ile Pro Gly Gln Ala Glu Ile Arg His
100 105 110
gct atg ctt ata aga att taa 357
Ala Met Leu Ile Arg Ile
115
<210>27
<211>118
<212>PRT
<213>B群链球菌
<400>27
Met Lys Asn Ile Thr Lys Leu Ser Thr Val Ala Leu Ser Leu Leu Leu
1 5 10 15
Cys Thr Ala Cys Ala Ala Ser Asn Thr Ser Thr Ser Lys Thr Gln Ser
20 25 30
His His Pro Lys Gln Thr Lys Leu Thr Asp Lys Gln Lys Glu Glu Pro
35 40 45
Lys Asn Lys Glu Ala Ala Asp Gln Glu Met His Pro Gln Gly Ala Val
50 55 60
Asp Leu Thr Lys Tyr Lys Ala Lys Pro Val Lys Asp Tyr Gly Lys Lys
65 70 75 80
Ile Asp Val Gly Asp Gly Lys Lys Met Asn Ile Tyr Glu Thr Gly Gln
85 90 95
Gly Lys Ile Pro Ile Val Phe Ile Pro Gly Gln Ala Glu Ile Arg His
100 105 110
Ala Met Leu Ile Arg Ile
115
<210>28
<211>1191
<212>DNA
<213>B群链球菌
<220>
<221>CDS
<222>(1)..(1191)
<400>28
gtg aat gaa tcg acc atc aga aaa gaa ttt aaa ata gtt gtt ttt aaa 48
Val Asn Glu Ser Thr Ile Arg Lys Glu Phe Lys Ile Val Val Phe Lys
1 5 10 15
tgg atc tta aat aat caa gca gtt att gct ctc atg att acc ttt ttg 96
Trp Ile Leu Asn Asn Gln Ala Val Ile Ala Leu Met Ile Thr Phe Leu
20 25 30
gta ttt tta acg att ttt att ttt acc aaa atc tct ttt atg ttt aaa 144
Val Phe Leu Thr Ile Phe Ile Phe Thr Lys Ile Ser Phe Met Phe Lys
35 40 45
cct gtg ttt gat ttt ctt gct gtg ctg ata ttg ccg ctt gta att tct 192
Pro Val Phe Asp Phe Leu Ala Val Leu Ile Leu Pro Leu Val Ile Ser
50 55 60
ggc ttg ctt tat tac cta tta aaa cct atg gtt aca ttt tta gag aag 240
Gly Leu Leu Tyr Tyr Leu Leu Lys Pro Met Val Thr Phe Leu Glu Lys
65 70 75 80
cgg gga att aag cgt gta aca gcg ata tta tca gtt ttt act att ata 288
Arg Gly Ile Lys Arg Val Thr Ala Ile Leu Ser Val Phe Thr Ile Ile
85 90 95
atc ctt ctg tta att tgg gca atg tct agt ttt att ccc atg atg agt 336
Ile Leu Leu Leu Ile Trp Ala Met Ser Ser Phe Ile Pro Met Met Ser
100 105 110
aat caa tta cgc cat ttt atg gaa gat ctc cct tca tat gtg aat aaa 384
Asn Gln Leu Arg His Phe Met Glu Asp Leu Pro Ser Tyr Val Asn Lys
115 120 125
gtg caa atg gaa aca agt tcg ttt ata gat cac aac cct tgg tta aaa 432
Val Gln Met Glu Thr Ser Ser Phe Ile Asp His Asn Pro Trp Leu Lys
130 135 140
tct tat aaa ggg gaa ata tcg agc atg tta tct aat atc agt agc caa 480
Ser Tyr Lys Gly Glu Ile Ser Ser Met Leu Ser Asn Ile Ser Ser Gln
145 150 155 160
gcg gtc tct tat gct gaa aaa ttt tca aag aat gtt tta gat tgg gca 528
Ala Val Ser Tyr Ala Glu Lys Phe Ser Lys Asn Val Leu Asp Trp Ala
165 170 175
gga aat tta gct agt aca gtt gca cgt gtg aca gta gca aca atc atg 576
Gly Asn Leu Ala Ser Thr Val Ala Arg Val Thr Val Ala Thr Ile Met
180 185 190
gct ccc ttt att ttg ttt tat ctt tta aga gat agt cgc aac atg aag 624
Ala Pro Phe Ile Leu Phe Tyr Leu Leu Arg Asp Ser Arg Asn Met Lys
195 200 205
aat ggt ttc tta atg gtt tta cca acc aaa cta cgc caa cca gct gat 672
Asn Gly Phe Leu Met Val Leu Pro Thr Lys Leu Arg Gln Pro Ala Asp
210 215 220
cgt att ttg cga gaa atg aat agt caa atg tca gga tat gtg caa gga 720
Arg Ile Leu Arg Glu Met Asn Ser Gln Met Ser Gly Tyr Val Gln Gly
225 230 235 240
caa atc att gtt gct att act gtt ggt gtt att ttt tca ata atg tat 768
Gln Ile Ile Val Ala Ile Thr Val Gly Val Ile Phe Ser Ile Met Tyr
245 250 255
agt att ata ggc ctt aga tat ggc gtg aca tta ggg att att gcc ggt 816
Ser Ile Ile Gly Leu Arg Tyr Gly Val Thr Leu Gly Ile Ile Ala Gly
260 265 270
gtg tta aat atg gtt ccc tat ttg gga agt ttt gtc gcc caa att cca 864
Val Leu Asn Met Val Pro Tyr Leu Gly Ser Phe Val Ala Gln Ile Pro
275 280 285
gtg ttt atc tta gcg ctt gtc gca gga cct gtt atg gtt gtt aaa gtt 912
Val Phe Ile Leu Ala Leu Val Ala Gly Pro Val Met Val Val Lys Val
290 295 300
gcg att gtt ttt gtt att gag caa act cta gag gga cgc ttt gtc tca 960
Ala Ile Val Phe Val Ile Glu Gln Thr Leu Glu Gly Arg Phe Val Ser
305 310 315 320
cct ttg gtt tta ggt aat aaa ctt agc att cat cca att aca att atg 1008
Pro Leu Val Leu Gly Asn Lys Leu Ser Ile His Pro Ile Thr Ile Met
325 330 335
ttt att tta tta acc tct gga gcg atg ttt ggt gtt tgg gga gta ttc 1056
Phe Ile Leu Leu Thr Ser Gly Ala Met Phe Gly Val Trp Gly Val Phe
340 345 350
ctc agt att ccg att tat gca tct atc aaa gtt gtt gtt aaa gaa ttg 1104
Leu Ser Ile Pro Ile Tyr Ala Ser Ile Lys Val Val Val Lys Glu Leu
355 360 365
ttt gat tgg tac aaa gct gtc agt ggg cta tat aca ata gat gtt gtt 1152
Phe Asp Trp Tyr Lys Ala Val Ser Gly Leu Tyr Thr Ile Asp Val Val
370 375 380
act gaa gaa aga agt gaa gaa gtt aaa aat gtt gaa tag 1191
Thr Glu Glu Arg Ser Glu Glu Val Lys Asn Val Glu
385 390 395
<210>29
<211>396
<212>PRT
<213>B群链球菌
<400>29
Val Asn Glu Ser Thr Ile Arg Lys Glu Phe Lys Ile Val Val Phe Lys
1 5 10 15
Trp Ile Leu Asn Asn Gln Ala Val Ile Ala Leu Met Ile Thr Phe Leu
20 25 30
Val Phe Leu Thr Ile Phe Ile Phe Thr Lys Ile Ser Phe Met Phe Lys
35 40 45
Pro Val Phe Asp Phe Leu Ala Val Leu Ile Leu Pro Leu Val Ile Ser
50 55 60
Gly Leu Leu Tyr Tyr Leu Leu Lys Pro Met Val Thr Phe Leu Glu Lys
65 70 75 80
Arg Gly Ile Lys Arg Val Thr Ala Ile Leu Ser Val Phe Thr Ile Ile
85 90 95
Ile Leu Leu Leu Ile Trp Ala Met Ser Ser Phe Ile Pro Met Met Ser
100 105 110
Asn Gln Leu Arg His Phe Met Glu Asp Leu Pro Ser Tyr Val Asn Lys
115 120 125
Val Gln Met Glu Thr Ser Ser Phe Ile Asp His Asn Pro Trp Leu Lys
130 135 140
Ser Tyr Lys Gly Glu Ile Ser Ser Met Leu Ser Asn Ile Ser Ser Gln
145 150 155 160
Ala Val Ser Tyr Ala Glu Lys Phe Ser Lys Asn Val Leu Asp Trp Ala
165 170 175
Gly Asn Leu Ala Ser Thr Val Ala Arg Val Thr Val Ala Thr Ile Met
180 185 190
Ala Pro Phe Ile Leu Phe Tyr Leu Leu Arg Asp Ser Arg Asn Met Lys
195 200 205
Asn Gly Phe Leu Met Val Leu Pro Thr Lys Leu Arg Gln Pro Ala Asp
210 215 220
Arg Ile Leu Arg Glu Met Asn Ser Gln Met Ser Gly Tyr Val Gln Gly
225 230 235 240
Gln Ile Ile Val Ala Ile Thr Val Gly Val Ile Phe Ser Ile Met Tyr
245 250 255
Ser Ile Ile Gly Leu Arg Tyr Gly Val Thr Leu Gly Ile Ile Ala Gly
260 265 270
Val Leu Asn Met Val Pro Tyr Leu Gly Ser Phe Val Ala Gln Ile Pro
275 280 285
Val Phe Ile Leu Ala Leu Val Ala Gly Pro Val Met Val Val Lys Val
290 295 300
Ala Ile Val Phe Val Ile Glu Gln Thr Leu Glu Gly Arg Phe Val Ser
305 310 315 320
Pro Leu Val Leu Gly Asn Lys Leu Ser Ile His Pro Ile Thr Ile Met
325 330 335
Phe Ile Leu Leu Thr Ser Gly Ala Met Phe Gly Val Trp Gly Val Phe
340 345 350
Leu Ser Ile Pro Ile Tyr Ala Ser Ile Lys Val Val Val Lys Glu Leu
355 360 365
Phe Asp Trp Tyr Lys Ala Val Ser Gly Leu Tyr Thr Ile Asp Val Val
370 375 380
Thr Glu Glu Arg Ser Glu Glu Val Lys Asn Val Glu
385 390 395
<210>30
<211>1230
<212>DNA
<213>B群链球菌
<220>
<221>CDS
<222>(1)..(1230)
<400>30
atg ttt atg gga atc cca caa tat ttc ttc tac ctt atc tta gct gtc 48
Met Phe Met Gly Ile Pro Gln Tyr Phe Phe Tyr Leu Ile Leu Ala Val
1 5 10 15
cta cca att tac atc ggc tta ttc ttt aag aag cgt ttt gcc tta tat 96
Leu Pro Ile Tyr Ile Gly Leu Phe Phe Lys Lys Arg Phe Ala Leu Tyr
20 25 30
gag att att ttt agt cta agt ttt att gta atg atg ttg act ggt agt 144
Glu Ile Ile Phe Ser Leu Ser Phe Ile Val Met Met Leu Thr Gly Ser
35 40 45
act ttt aat caa ttg aag tca cta ttg gca tac gtt gtc gga cag tct 192
Thr Phe Asn Gln Leu Lys Ser Leu Leu Ala Tyr Val Val Gly Gln Ser
50 55 60
ctg cta gtt ttt atc tat aaa gct tac cgg aaa cga ttt aat cat act 240
Leu Leu Val Phe Ile Tyr Lys Ala Tyr Arg Lys Arg Phe Asn His Thr
65 70 75 80
ttg gtc ttt tat gta acg gtt tgt tta tct att ttt ccg cta ttt ttg 288
Leu Val Phe Tyr Val Thr Val Cys Leu Ser Ile Phe Pro Leu Phe Leu
85 90 95
gta aaa tta att cca gct ata tct gag gat ggg cat cag tca ctt ttt 336
Val Lys Leu Ile Pro Ala Ile Ser Glu Asp Gly His Gln Ser Leu Phe
100 105 110
ggg ttt cta gga att tct tac ctt act ttt aga gct gtt gct atg att 384
Gly Phe Leu Gly Ile Ser Tyr Leu Thr Phe Arg Ala Val Ala Met Ile
115 120 125
att gaa atg aga gac ggt gtc ttg aaa gaa ttt act tta tgg gaa ttc 432
Ile Glu Met Arg Asp Gly Val Leu Lys Glu Phe Thr Leu Trp Glu Phe
130 135 140
tta aga ttt tta ctc ttc ttt cca act ttc tca agt gga cca att gat 480
Leu Arg Phe Leu Leu Phe Phe Pro Thr Phe Ser Ser Gly Pro Ile Asp
145 150 155 160
cgt ttt aaa cga ttc aat gag gat tac att aat atc cca gat cga aac 528
Arg Phe Lys Arg Phe Asn Glu Asp Tyr Ile Asn Ile Pro Asp Arg Asn
165 170 175
gaa ctc cta gat atg tta ggt caa gcg att cat tat ttg atg tta ggt 576
Glu Leu Leu Asp Met Leu Gly Gln Ala Ile His Tyr Leu Met Leu Gly
180 185 190
ttt ctc tat aag ttt att tta gcc tat att ttt gga agt ctg att atg 624
Phe Leu Tyr Lys Phe Ile Leu Ala Tyr Ile Phe Gly Ser Leu Ile Met
195 200 205
cct cct cta aaa gaa tta gcg cta gaa cag ggt ggt gtg ttt aat tgg 672
Pro Pro Leu Lys Glu Leu Ala Leu Glu Gln Gly Gly Val Phe Asn Trp
210 215 220
cca aca ctt ggg gtt atg tat gcc ttt ggt ttt gat ttg ttc ttt gat 720
Pro Thr Leu Gly Val Met Tyr Ala Phe Gly Phe Asp Leu Phe Phe Asp
225 230 235 240
ttt gca ggt tac aca atg ttt gcg ttg gct att tct aac cta atg ggg 768
Phe Ala Gly Tyr Thr Met Phe Ala Leu Ala Ile Ser Asn Leu Met Gly
245 250 255
att aag tct ccg att aac ttt gac aaa cct ttc aaa tca cgc gac cta 816
Ile Lys Ser Pro Ile Asn Phe Asp Lys Pro Phe Lys Ser Arg Asp Leu
260 265 270
aaa gaa ttt tgg aat aga tgg cat atg agc ctt tct ttc tgg ttt aga 864
Lys Glu Phe Trp Asn Arg Trp His Met Ser Leu Ser Phe Trp Phe Arg
275 280 285
gac ttt gtt ttc atg agg ctt gtt aag ctt tta gtt aaa aat aaa gtt 912
Asp Phe Val Phe Met Arg Leu Val Lys Leu Leu Val Lys Asn Lys Val
290 295 300
ttt aaa aac cgt aat gtt act tca agt gta gct tat att atc aat atg 960
Phe Lys Asn Arg Asn Val Thr Ser Ser Val Ala Tyr Ile Ile Asn Met
305 310 315 320
ctt ctt atg gga ttc tgg cat ggg tta act tgg tac tat ata gcc tat 1008
Leu Leu Met Gly Phe Trp His Gly Leu Thr Trp Tyr Tyr Ile Ala Tyr
325 330 335
ggt ctc ttt cat ggg att ggc cta gtt att aat gac gct tgg gta cgt 1056
Gly Leu Phe His Gly Ile Gly Leu Val Ile Asn Asp Ala Trp Val Arg
340 345 350
aag aag aaa aat ayt aat aaa gaa aga aga ttg gct aaa aaa cca ctt 1104
Lys Lys Lys Asn Xaa Asn Lys Glu Arg Arg Leu Ala Lys Lys Pro Leu
355 360 365
tta cca gaa aac aaa tgg act tat gct ttg ggt gtc ttc atc acc ttt 1152
Leu Pro Glu Asn Lys Trp Thr Tyr Ala Leu Gly Val Phe Ile Thr Phe
370 375 380
aat gta gtt atg ttt tct ttc ttg att ttt tca gga ttt tta gat ctt 1200
Asn Val Val Met Phe Ser Phe Leu Ile Phe Ser Gly Phe Leu Asp Leu
385 390 395 400
ttg tgg ttc cca caa ccg cat aac aaa taa 1230
Leu Trp Phe Pro Gln Pro His Asn Lys
405 410
<210>31
<211>409
<212>PRT
<213>B群链球菌
<400>31
Met Phe Met Gly Ile Pro Gln Tyr Phe Phe Tyr Leu Ile Leu Ala Val
1 5 10 15
Leu Pro Ile Tyr Ile Gly Leu Phe Phe Lys Lys Arg Phe Ala Leu Tyr
20 25 30
Glu Ile Ile Phe Ser Leu Ser Phe Ile Val Met Met Leu Thr Gly Ser
35 40 45
Thr Phe Asn Gln Leu Lys Ser Leu Leu Ala Tyr Val Val Gly Gln Ser
50 55 60
Leu Leu Val Phe Ile Tyr Lys Ala Tyr Arg Lys Arg Phe Asn His Thr
65 70 75 80
Leu Val Phe Tyr Val Thr Val Cys Leu Ser Ile Phe Pro Leu Phe Leu
85 90 95
Val Lys Leu Ile Pro Ala Ile Ser Glu Asp Gly His Gln Ser Leu Phe
100 105 110
Gly Phe Leu Gly Ile Ser Tyr Leu Thr Phe Arg Ala Val Ala Met Ile
115 120 125
Ile Glu Met Arg Asp Gly Val Leu Lys Glu Phe Thr Leu Trp Glu Phe
130 135 140
Leu Arg Phe Leu Leu Phe Phe Pro Thr Phe Ser Ser Gly Pro Ile Asp
145 150 155 160
Arg Phe Lys Arg Phe Asn Glu Asp Tyr Ile Asn Ile Pro Asp Arg Asn
165 170 175
Glu Leu Leu Asp Met Leu Gly Gln Ala Ile His Tyr Leu Met Leu Gly
180 185 190
Phe Leu Tyr Lys Phe Ile Leu Ala Tyr Ile Phe Gly Ser Leu Ile Met
195 200 205
Pro Pro Leu Lys Glu Leu Ala Leu Glu Gln Gly Gly Val Phe Asn Trp
210 215 220
Pro Thr Leu Gly Val Met Tyr Ala Phe Gly Phe Asp Leu Phe Phe Asp
225 230 235 240
Phe Ala Gly Tyr Thr Met Phe Ala Leu Ala Ile Ser Asn Leu Met Gly
245 250 255
Ile Lys Ser Pro Ile Asn Phe Asp Lys Pro Phe Lys Ser Arg Asp Leu
260 265 270
Lys Glu Phe Trp Asn Arg Trp His Met Ser Leu Ser Phe Trp Phe Arg
275 280 285
Asp Phe Val Phe Met Arg Leu Val Lys Leu Leu Val Lys Asn Lys Val
290 295 300
Phe Lys Asn Arg Asn Val Thr Ser Ser Val Ala Tyr Ile Ile Asn Met
305 310 315 320
Leu Leu Met Gly Phe Trp His Gly Leu Thr Trp Tyr Tyr Ile Ala Tyr
325 330 335
Gly Leu Phe His Gly Ile Gly Leu Val Ile Asn Asp Ala Trp Val Arg
340 345 350
Lys Lys Lys Asn Xaa Asn Lys Glu Arg Arg Leu Ala Lys Lys Pro Leu
355 360 365
Leu Pro Glu Asn Lys Trp Thr Tyr Ala Leu Gly Val Phe Ile Thr Phe
370 375 380
Asn Val Val Met Phe Ser Phe Leu Ile Phe Ser Gly Phe Leu Asp Leu
385 390 395 400
Leu Trp Phe Pro Gln Pro His Asn Lys
405
<210>32
<211>100
<212>DNA
<213>B群链球菌
<220>
<221>CDS
<222>(1)..(99)
<400>32
atg aat aaa ata acg aca tta tca acc atc gcc ctg act tta atg ctt 48
Met Asn Lys Ile Thr Thr Leu Ser Thr Ile Ala Leu Thr Leu Met Leu
1 5 10 15
tgc gtt gga tgt tct gcc aat aaa gat aat caa aaa act aaa act gag 96
Cys Val Gly Cys Ser Ala Asn Lys Asp Asn Gln Lys Thr Lys Thr Glu
20 25 30
gat c 100
Asp
<210>33
<211>33
<212>PRT
<213>B群链球菌
<400>33
Met Asn Lys Ile Thr Thr Leu Ser Thr Ile Ala Leu Thr Leu Met Leu
1 5 10 15
Cys Val Gly Cys Ser Ala Asn Lys Asp Asn Gln Lys Thr Lys Thr Glu
20 25 30
Asp
<210>34
<211>654
<212>DNA
<213>B群链球菌
<220>
<221>CDS
<222>(1)..(654)
<400>34
gat cga ggc tat caa gaa gca atg gct aaa cta agg aaa act tac ggc 48
Asp Arg Gly Tyr Gln Glu Ala Met Ala Lys Leu Arg Lys Thr Tyr Gly
1 5 10 15
gaa tat ggt tta ggg gtt tct aca gga tta gat tta cct gaa tca gaa 96
Glu Tyr Gly Leu Gly Val Ser Thr Gly Leu Asp Leu Pro Glu Ser Glu
20 25 30
ggt tat gta cct gga aaa tac agc tta gga aca act cta atg gaa tcg 144
Gly Tyr Val Pro Gly Lys Tyr Ser Leu Gly Thr Thr Leu Met Glu Ser
35 40 45
ttc ggt cag tat gat gcc tat aca cca atg caa ctt ggt cag tat atc 192
Phe Gly Gln Tyr Asp Ala Tyr Thr Pro Met Gln Leu Gly Gln Tyr Ile
50 55 60
tca act att gcg aat aat ggg aat cgt tta gca cct cac gtg gtt tca 240
Ser Thr Ile Ala Asn Asn Gly Asn Arg Leu Ala Pro His Val Val Ser
65 70 75 80
gat atc tat gaa ggg aat gat tct aat aag ttc gct caa ttg gtt cgt 288
Asp Ile Tyr Glu Gly Asn Asp Ser Asn Lys Phe Ala Gln Leu Val Arg
85 90 95
tca atc act cct aaa aca cta aat aag ata gct atc tca gat caa gag 336
Ser Ile Thr Pro Lys Thr Leu Asn Lys Ile Ala Ile Ser Asp Gln Glu
100 105 110
tta gcc att att caa gaa ggt ttt tat aac gtt gtc aat agt gga agt 384
Leu Ala Ile Ile Gln Glu Gly Phe Tyr Asn Val Val Asn Ser Gly Ser
115 120 125
ggc tat gca act ggt acg tca atg agg ggg aat gtg aca acc att agy 432
Gly Tyr Ala Thr Gly Thr Ser Met Arg Gly Asn Val Thr Thr Ile Xaa
130 135 140
ggt aaa act ggt acc gct gaa aca ttt gct aaa aat ata aat gga caa 480
Gly Lys Thr Gly Thr Ala Glu Thr Phe Ala Lys Asn Ile Asn Gly Gln
145 150 155 160
aca gtt tct acc tac aac tta aac gct att gcc tac gat act aat cgt 528
Thr Val Ser Thr Tyr Asn Leu Asn Ala Ile Ala Tyr Asp Thr Asn Arg
165 170 175
aaa ata gca gta gcg gta atg tat ccg cat gtt aca act gat aca aca 576
Lys Ile Ala Val Ala Val Met Tyr Pro His Val Thr Thr Asp Thr Thr
180 185 190
aaa tcc cat caa tta gtt gca cga gat atg att gat caa tat att tca 624
Lys Ser His Gln Leu Val Ala Arg Asp Met Ile Asp Gln Tyr Ile Ser
195 200 205
cag tca cag gac aat aag aga gga cat tga 654
Gln Ser Gln Asp Asn Lys Arg Gly His
210 215
<210>35
<211>217
<212>PRT
<213>B群链球菌
<400>35
Asp Arg Gly Tyr Gln Glu Ala Met Ala Lys Leu Arg Lys Thr Tyr Gly
1 5 10 15
Glu Tyr Gly Leu Gly Val Ser Thr Gly Leu Asp Leu Pro Glu Ser Glu
20 25 30
Gly Tyr Val Pro Gly Lys Tyr Ser Leu Gly Thr Thr Leu Met Glu Ser
35 40 45
Phe Gly Gln Tyr Asp Ala Tyr Thr Pro Met Gln Leu Gly Gln Tyr Ile
50 55 60
Ser Thr Ile Ala Asn Asn Gly Asn Arg Leu Ala Pro His Val Val Ser
65 70 75 80
Asp Ile Tyr Glu Gly Asn Asp Ser Asn Lys Phe Ala Gln Leu Val Arg
85 90 95
Ser Ile Thr Pro Lys Thr Leu Asn Lys Ile Ala Ile Ser Asp Gln Glu
100 105 110
Leu Ala Ile Ile Gln Glu Gly Phe Tyr Asn Val Val Asn Ser Gly Ser
115 120 125
Gly Tyr Ala Thr Gly Thr Ser Met Arg Gly Asn Val Thr Thr Ile Xaa
130 135 140
Gly Lys Thr Gly Thr Ala Glu Thr Phe Ala Lys Asn Ile Asn Gly Gln
145 150 155 160
Thr Val Ser Thr Tyr Asn Leu Asn Ala Ile Ala Tyr Asp Thr Asn Arg
165 170 175
Lys Ile Ala Val Ala Val Met Tyr Pro His Val Thr Thr Asp Thr Thr
180 185 190
Lys Ser His Gln Leu Val Ala Arg Asp Met Ile Asp Gln Tyr Ile Ser
195 200 205
Gln Ser Gln Asp Asn Lys Arg Gly His
210 215
Claims (10)
1.用于治疗用途的可从B群链球菌中获得的在此处被鉴定为pho1-13,pho3-21,pho2-15,pho3-18,pho3-22,pho3-3,pho3-17,pho2-2,pho1-5,pho3-1,pho3-23,pho3-50,pho1-14,pho2-10,pho3-14,pho3-24和pho3-29的肽或其同源物或其功能性片段,所述同源物或功能性片段保留了与所述肽诱发相同的免疫应答的能力。
2.权利要求1的肽,包含在此处被鉴定为SEQ ID NOS.2,4,6,8,10,11,13,15,17,19,21,23,25,27,29,31,33和35的任一氨基酸序列。
3.一种编码用于治疗用途的权利要求1或权利要求2的肽的多核苷酸,。
4.一种表达权利要求1或权利要求2的肽的转化宿主。
5.一种疫苗,包含权利要求1或权利要求2的肽。
6.权利要求1-4中任何一项的产品用于筛选潜在药物或用于毒性检测的用途。
7.权利要求1-4中任何一项的产品在制备用于治疗或预防与B群链球菌微生物感染相关的病症的药物中的用途。
8.权利要求7的用途,其中的感染是病灶感染。
9.权利要求7的用途,其中的感染是尿道感染。
10.针对权利要求1或权利要求2的肽产生的抗体。
Applications Claiming Priority (35)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB9828354.2 | 1998-12-22 | ||
GB9828356.7 | 1998-12-22 | ||
GB9828352.6 | 1998-12-22 | ||
GB9828345.0 | 1998-12-22 | ||
GBGB9828354.2A GB9828354D0 (en) | 1998-12-22 | 1998-12-22 | Protein and compositions containing it |
GB9828355.9 | 1998-12-22 | ||
GB9828353.4 | 1998-12-22 | ||
GB9828350.0 | 1998-12-22 | ||
GBGB9828357.5A GB9828357D0 (en) | 1998-12-22 | 1998-12-22 | Protein and compositions containing it |
GB9828359.1 | 1998-12-22 | ||
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PCT/GB1999/004377 WO2000037646A2 (en) | 1998-12-22 | 1999-12-22 | Group b streptococcus proteins, and their use |
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CN 99814780 Division CN1331745A (zh) | 1998-12-22 | 1999-12-22 | 基因和蛋白质,及它们的用途 |
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WO2018149216A1 (zh) * | 2017-02-16 | 2018-08-23 | 清华大学 | 肺炎链球菌疫苗 |
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US7427475B2 (en) * | 2003-11-18 | 2008-09-23 | Mayo Foundation For Medical Education And Research | Detection of group B streptococcus |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2018149216A1 (zh) * | 2017-02-16 | 2018-08-23 | 清华大学 | 肺炎链球菌疫苗 |
US10960066B2 (en) | 2017-02-16 | 2021-03-30 | Tsinghua University | Streptococcus pneumoniae vaccine |
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