CN1437653A - 抗原多肽 - Google Patents
抗原多肽 Download PDFInfo
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- CN1437653A CN1437653A CN01811545A CN01811545A CN1437653A CN 1437653 A CN1437653 A CN 1437653A CN 01811545 A CN01811545 A CN 01811545A CN 01811545 A CN01811545 A CN 01811545A CN 1437653 A CN1437653 A CN 1437653A
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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Abstract
本发明涉及一种鉴定由病原微生物所表达的抗原多肽的方法；包含所述多肽的疫苗；制备所述多肽的重组方法；和针对所述多肽的治疗用抗体。
Description
本发明涉及一种鉴定由病原微生物所表达的抗原多肽的方法；包含所述多肽的疫苗；制备所述多肽的重组方法；和针对所述多肽的治疗用抗体。
微生物引起的大量致死或致弱的疾病，影响着全世界数百万人。控制微生物的现有方法包括应用抗微生物制剂(抗生素)和消毒剂。它们被证明是有问题的，由于暴露在这些制剂的环境中所形成的显著的选择性压力导致了耐药性微生物的产生，这些微生物能够躲避抗微生物制剂的作用。例如，近来已发现微生物对三氯生产生了耐药性，而在家庭及工业环境中使用的许多消毒剂中都添加有三氯生。
一个越来越引起争议的问题是许多重要的病原微生物进化出了对抗生素的耐药株。
例如，但并不限于所举的例子，估计全世界超过5千万人感染了耐药的结核病(TB)(数字来自世界卫生组织，1998)。过去使用抗生素治疗结核病依赖于单一药物(如乙硫异烟胺)，因此产生了较高频率的耐药性。由于这个原因，现在治疗结核病采用联合用药。但即使联合用药进行治疗，由至少对一种用于治疗结核病的药物产生耐药性的菌株所引起的治疗失败的比率仍然接近50％。导致TB的分枝杆菌是一种慢性生长的细菌，需要花费很长时间消灭它。所以，联合用药若要产生疗效，TB患者必须每天服用组合药物至少6个月。病人通常必须每天服用两种或更多种药物，并需要相当长的治疗期限。许多病人仅是断续服药而没有完成彻底根除分枝杆菌感染的全部疗程。再者，TB与艾滋病感染有密切联系，因而TB的产生是与免疫抑制紧密相关的。
抗TB的疫苗已经应用了许多年。作为一种对潜在的可能感染TB的大量人群的安全和廉价的预防手段，卡介苗(BCG)已在长时间内广泛应用于全世界。BCG是从牛分枝杆菌获得的减毒活疫苗。但是预防接种对TB感染的效果不大，所以BCG对全面控制这一疾病的作用是有限的。
金黄色葡萄球菌是病原微生物对抗生素产生耐药性的另一个例子。金黄色葡萄球菌是一种通常寄居在约20-40％普通健康人鼻腔上皮内表面的细菌，也常在人皮肤上发现，通常不会引起疾病。但在某些场合，特别是当皮肤受损时，这种细菌能引起感染。在医院里这是一个特殊的问题，因为在那里病人会进行外科手术和/或服用免疫抑制药物。这些病人由于他们所接受的治疗更易受金黄色葡萄球菌的感染。近年来已产出现了金黄色葡萄球菌的耐药株。对甲氧苯青霉素的耐药株已很普遍，这些耐药株也对另外几种抗生素有耐药性。目前对金黄色葡萄球菌还没有有效的预防接种措施。在美国，每年两百万住院感染中的13％是由金黄色葡萄球菌感染引起的。这表示260,000人感染金黄色葡萄球菌，其中60-80,000人死亡。
因此，金黄色葡萄球菌是一种重要的人类病原菌，能引起许多威胁生命的疾病，包括败血症、心内膜炎、关节炎和中毒性休克。其致病力是由其微生物的多样性及其致病成分的毒力决定的。致病原因是多因素的，任何单一致病成分均不能解释一个特定的感染，见Projan，S.J.& Novick，R.P.(1997)著《人类疾病中的葡萄球菌》(Crossley，K.B.& Archer，G.L.，eds.)pp.55-81。
在感染初期，及发展阶段，微生物的需要及其环境发生改变，相应地，金黄色葡萄球菌所产生的致病毒素随之发生改变。在感染开始时，病原体粘附于宿主组织是关键性的，于是便产生了大量与在细胞表面粘附相关的蛋白质，包括胶原结合蛋白、血纤蛋白原结合蛋白和纤粘连蛋白结合蛋白。病原体还具有产生能减少吞噬作用或是干扰细胞被循环抗体识别的因子的能力，从而逃避宿主的防御系统。
通常，感染病灶会发展为一个脓肿，其中细菌大量滋生。金黄色葡萄球菌通过产生一定数量的感受肽能监测其自身的细胞密度。肽的积累以及所伴随的生理变化，引起细胞的营养不足，从而使细胞所产生的致病毒素从粘附素转变为引起浸润和组织穿透的组分。这包括多种溶血素、蛋白酶和其他降解酶等。
在任何感染过程中，金黄色葡萄球菌所产生的致病毒素是随环境和生理刺激而改变的。这些刺激取决于体内局部的环境并随着感染的进程而改变。由于对体内的情况所知甚少，并且某些毒素组分似乎仅能在体内的环境下产生，所以一些可能成为疫苗的组分不能为早期的技术所发现。
近代药物历史中最重要的发展之一是疫苗的发展，其对各种病原微生物的感染提供了预防性保护。许多疫苗是由灭活的或减毒的病原制成的，然后注射给个体。经免疫的个体通过产生体液(抗体)和细胞(溶细胞的T细胞，CTL’s)应答而做出反应。例如，肝炎疫苗的制备是通过加热灭活病毒和用像甲醛这样的交联剂处理。减毒病原的一个代表例子是由活病原弱化产生的脊髓灰质炎疫苗。
但是对特定疾病应用减毒疫苗是存在顾虑的，因为缺乏对于减毒过程的本质和条件的病理学知识的了解。这个问题对于特定病毒制剂而言尤其突出，这是因为病毒，特别是逆转录病毒，具有错误倾向的复制周期，导致含有病毒的基因产生能够传代的突变，其结果是被用做疫苗的抗原决定簇的发生改变。替代使用灭活的或减毒的病原的一种方法是鉴别出免疫系统对其特别敏感的病原表位。由此，许多由病原微生物在感染过程中产生的致病毒素，对于开发具有保护个体免于受到特定致病微生物感染作用的疫苗是特别有用的。
发展亚单位疫苗(疫苗其免疫原是由特定的病原微生物表达的一个蛋白质或复合体的一个片段或亚基)已经成为医学研究的焦点。对鉴别出用于发展亚单位疫苗的候选分子的需求，显然不仅仅是因为近来抗生素耐药性的出现已经成为用传统化学疗法控制致病微生物的严重障碍。已经发展了许多方法来确定有可能用作疫苗的抗原多肽。在此举一个方法以作说明。许多年来已知肿瘤细胞能产生一些肿瘤细胞特异性抗原，其中一些出现在肿瘤细胞表面。免疫系统识别这些抗原并将其作为外来物，然后产生针对自身抗原的抗体，这叫自身抗体或自身抗血清。
这种技术之一是重组表达克隆抗原的血清学识别，简写成SEREX。
典型地说，这一技术包括从肿瘤组织中提取RNA，然后从分离的总RNA中的选择性富集mRNA。mRNA用病毒逆转录酶反转录为cDNA。这样合成的cDNA再被克隆进入一个表达载体，并且转化进入一个适当的细菌株。转化的细菌被接种到一个营养适宜的琼脂平板上，在适宜的生长条件下，亚克隆的cDNA在细菌细胞中由表达载体来表达。应用基于噬菌体的表达载体可导致细胞自然溶解，例如λ噬菌体或基于噬菌粒的载体，通过它们的溶解循环引起细胞溶解。释放的多肽被转移至一种合适的膜支持物(如硝酸纤维素，尼龙)，并暴露于从最初自其分离肿瘤组织的病人中获得的自身抗血清。免疫筛选法可以用于从病人肿瘤组织中鉴定出过量表达或不恰当表达的基因。
我们使用这种技术来鉴定感染过程中由病原微生物所表达的抗原多肽。感染中产生的自身抗血清，被用于筛选一个由基因组DNA产生的表达文库，以鉴定和克隆抗原。
本发明最广义的方面是涉及在感染中由病原微生物表达的抗原多肽的鉴定。
按照本发明的第一方面，提供一种用于鉴定抗原多肽的方法，包括：
(i)提供一个编码病原微生物的基因或部分基因序列的核酸文库；
(ii)转化/转染所述核酸文库至一种宿主细胞；
(iii)提供有助于表达所述的转化/转染的基因或部分基因序列的条件；
(iv)将所述基因/部分基因序列表达的多肽与从感染或曾经感染过所述致病微生物的动物获得的自身抗血清相作用；以及
(v)纯化编码与所述自身抗血清相结合的多肽或部分多肽的核酸。
在本发明的优选方法中，所述的文库包含一个病原微生物的基因组DNA。
理想的所述病原微生物是细菌。
更优选地，所述的细菌微生物是从以下选择出来的：
金黄色葡萄球菌；表皮葡萄球菌；粪肠球菌；结核分枝杆菌；B族链球菌；肺炎链球菌；幽门螺杆菌；淋病奈瑟氏球菌；A族链球菌；布氏疏螺旋体；粗球孢菌；荚膜组织胞浆菌；B型脑膜炎奈瑟氏球菌；弗氏志贺氏菌；大肠杆菌；流感嗜血菌。
更优选地，所述病原微生物是葡萄球菌属细菌。理想的病原生物体是金黄色葡萄球菌或表皮葡萄球菌。
在本发明的一个更优选的实施方案中，所述核酸文库是一个λ文库，理想地，是一个λ表达文库。
按照本发明的第二个方面，提供了含有一个DNA序列的核酸分子，所述DNA序列选自：
(i)如SEQ ID NO：1-13中代表的DNA序列；
(ii)与上述(i)中确定的SEQ ID NO：1-13所示序列杂交并编码一种致病微生物所表达的多肽的DNA序列，以及
(iii)由(i)和(ii)中所确定的DNA序列的遗传密码所产生的简并DNA序列。
在本发明的一个更优选的实施方案中，所述核酸分子是基因组DNA。
在本发明的一个优选的实施方案中，提供了一种分离的核酸分子，所述核酸分子在严格杂交条件下与SEQ ID NO：1-13中所示序列退火。
严格的杂交/漂洗条件是本领域的公知常识。例如，核酸杂交体在0.1％×SSC，0.1％SDS中60℃下漂洗后是稳定的。本领域公知，如果已知核酸的序列，可以计算出最佳的杂交条件。例如，根据要进行杂交的核酸的GC含量，能将杂交条件确定下来。请阅Sambrook等(1989)著《分子克隆实验手册》。一个用于计算给定的同源核酸分子间杂交所需严格条件的普遍公式为：
Tm＝81.5℃+16.6Log[Na+]+0.41[％G+C]-0.63(％甲酰胺)
按照本发明的第三个方面，提供至少一种依照本发明的方法所鉴定的多肽。
在本发明的一个优选的实施方案中，根据本发明前面所述的任一方面或实施方案，所述多肽与一种微生物的感染致病力相关。
更优选地，所述多肽至少是SEQ ID NO：14-19之一或一部分。
按照本发明的第四个方面，提供了一种核酸分子，其特征在于所述的核酸分子是一个载体的一部分，所述载体适于促进由所述核酸分子编码的多肽的重组表达。
在本发明的一个优选的实施方案中，所说的载体是一种适应于进行原核基因表达的表达载体。或者，所述表达载体适应于进行真核基因表达。
典型地，所述的适应性包括，例如但不限于，提供介导细胞特异性表达的转录控制序列(启动子序列)。这些启动子序列可以是细胞特异性的，可诱导的或组成性的。
启动子是本领域所知的术语，为了清楚的目的，仅举一个例子，但不限于此例，以说明其如下的特征。增强子元件是顺式作用的核酸序列，通常位于一个基因的转录起始位点的5’端(增强子也可出现在基因序列的3’端或者甚至位于内含子序列内部，因此其不受位置的约束)。增强子的功能是增加与增强子连接的基因的转录频率。增强子的活性是响应与增强子元件特异性结合的反式作用转录因子(多肽)。转录因子的结合/活性(请看《真核转录因子》，DavidS Latchman，Academic Press Ltd，San Diego著)依赖于多种环境因素包括，例如但不限于，中间代谢产物(如葡萄糖，脂质)，环境作用因子(如光，热)。
启动子元件还包括TATA框和RNA聚合酶起始选择(RIS)序列，其功能是选择转录起始位点。这些序列也结合于多肽上，所述多肽，和其他事物一起，促进RNA聚合酶对转录起始点的选择。
适应性也包括提供选择标志和自动复制序列，两者均有助于所述载体在真核细胞或原核宿主中的维持。自动维持的载体称为附加载体。
促进载体编码基因表达的适应性包括提供转录终止/多聚腺苷酸序列。还包括提供内部核糖体进入位点(IRES)，其功能是最大表达排列在二顺反子或多顺反子表达盒中的载体编码基因。
这些适应性在本领域是熟知的。这里有一系列关于表达载体的构建和重组DNA的通用技术的出版物。请看，Sambrook等(1989)著《分子克隆实验手册》，冷泉港实验室，冷泉港，NY和其中的参考文献；Marston，F(1987)著《DNA克隆技术》；一本IRL出版的实用手册，Vol III IRL，英国牛津，《DNA克隆》：F M Ausubel等著，《分子生物学中的通用方案》，John Wiley & Sons，Inc.(1994)。
按照本发明的另外方面，提供了一种生产前述任一方面或实施方案所述多肽的方法，包括：
(i)提供一种用本发明的载体转化/转染的细胞；
(ii)在利于制备所述多肽的条件下培养所述细胞；以及
(iii)从所述细胞或其生长环境中纯化所述多肽。
在本发明的优选方法中，所述载体编码并因此为所述重组多肽提供一种促进所述多肽纯化的分泌信号。
按照本发明的第五个方面，本发明提供了一种用载体转化或转染的细胞或细胞系。
在本发明的一个优选的实施方案中，所述细胞是原核细胞。或者，所述细胞是选自真菌、昆虫、两栖动物、哺乳动物、植物的真核细胞。
按照本发明的另一方面，提供了一种疫苗，所述疫苗包含至少一种本发明的多肽。
理想地，所述疫苗还包含载体和/或佐剂。
载体和佐剂是以下述方式表述。某些多肽或肽抗原含有B-细胞表位但没有T细胞表位。通过在多肽/肽中加入T细胞表位，或通过将多肽/肽结合到一种含有多个T细胞表位的免疫原性载体蛋白上，如血兰蛋白或破伤风毒素，能大大增强免疫应答。结合物由抗原呈递细胞摄取，加工，并通过人白细胞抗原(HLA’s)II类分子呈递。这使得在T细胞的帮助下将针对源自载体表位的T细胞的特异性传递给对原始的抗原多肽/肽具有特异性的B细胞。这能增加抗体产生、分泌和同型转化。
佐剂是能够通过调节免疫细胞活性而增加对抗原的特异性免疫应答的一种物质或程序。佐剂的例子包括，例如但不限于，共刺激分子的激动抗体、弗氏佐剂、胞壁酰二肽、脂质体。因此佐剂是一种免疫调节剂。载体是一种免疫原性分子，当与第二个分子结合后会增强针对后者的免疫应答。
本发明另一方面提供了一种方法，所述方法包括通过对一种动物施用至少一种本发明的多肽或其一部分，或本发明的疫苗，使所述动物产生抵抗一种病原微生物的免疫力。
在本发明的一个优选的方法中，所述动物是人。
优选地，疫苗或抗原多肽能通过静脉内注射，肌肉注射，或皮下注射等直接注射接种。进一步地，疫苗或抗原多肽，或许还可以口服。
优选地，疫苗能抵抗金黄色葡萄球菌。
疫苗也可能抵抗表皮葡萄球菌。
显然，疫苗或抗原多肽对于控制或减轻除了人以外的其它动物的病情也是有效的，例如，但不限于例子，家庭宠物，家畜，马匹。
按照本发明的其它方面，还提供了一种抗体或至少其一个有效结合部分，所述抗体结合至少一种本发明的多肽。
在本发明的一个优选实施方案中，所述抗体是一种多克隆或单克隆抗体，其中所述抗体对所述多肽具有特异性。
或者，所述抗体是一种通过重组方法产生的嵌合抗体，其包含所述抗体的可变区与人类抗体的不变或恒定区。
在本发明的另一个替代实施方案中，所述抗体是通过重组方法产生的人源化抗体，是所述抗体的互补决定区域与一种人抗体的恒定区(C)和可变(V)区的读框的结合。
优选地，所述抗体被给予了一种标志，包括一种传统的标记或标签，例如放射性和/或荧光和/或表位的标记或标签。
优选地，针对所述的多肽的所述人源化的单克隆抗体，是由一种适合于转化或转染原核细胞或真核细胞的表达载体所产生的融合多肽。
抗体，也叫做免疫球蛋白，是一种对外来分子(抗原)具有特异性的蛋白分子。免疫球蛋白(Ig)是一类结构相关蛋白质，包括两对多肽链，一对是轻(L)(低分子量)链(κ或λ)，一对是重(H)链(γ，α，μ，δ和ε)，所有四条链通过二硫键结合在一起。重链和轻链都有结合抗原的区域，并且在Ig分子之间是高度可变的。另外，重链和轻链包括非可变或恒定区域。
轻链包括两个结构域。羧基-末端结构域在一种类型的轻链中是基本相同的，因此被称为“恒定”(C)区。氨基-末端结构域在轻链和轻链间是变化的并构成抗体的结合位点。因为它的可变性，它被称为“可变”(V)区。
Ig分子的重链分几个类型，α，μ，δ，ε，和γ(其中还分几个亚型)。装配好的Ig分子包括一个或多个由相同的两条重链和轻链组成的单位，并从它拥有的重链获得它的名称。这样，Ig便分成5个型：IgA，IgM，IgD，IgE和IgG(并因重链的不同而分成4个亚型，例如，IgG1，IgG2，IgG3和IgG4)。关于抗体结构和它们的不同功能的更详细的解释，可以参考《抗体的应用：一本实验室手册》，冷泉港实验室出版。
嵌合抗体是重组抗体，其中小鼠或大鼠抗体的所有可变区与人抗体的恒定区结合。人源化的抗体是重组杂交抗体，它融合了来自于啮齿类抗体的可变区的互补决定区与人抗体可变区的框区。也用了人抗体的恒定区。互补决定区(CDRs)位于抗体的重链和轻链的N-末端结构域，可变区的主要变化多集中在CDRs。这些区域构成位于抗体分子表面的环状结构。这些环状结构在抗体和抗原之间提供结合表面。
非人类动物的抗体可引起对外来抗体产生免疫应答，并由此被从血液循环中清除。注射到人机体中的嵌合抗体和人源化抗体具有弱的抗原性，因为在重组杂交抗体中啮齿类(即异类)抗体的量减少，而人的抗体区域不会引起免疫应答。它使得针对该抗体的免疫应答减弱，并减少了对抗体的清除。这显然对于应用治疗性抗体治疗人类疾病来说是很需要的。人源化抗体被设计为具有更少“异类”抗体区域，因此与嵌合抗体相比，人源化抗体是更弱的免疫原。
本发明的另一方面是提供一种载体，所述载体适用于按照本发明表达人源化的或嵌合体的抗体。
本发明进一步提供了一种细胞或细胞系，所述细胞或细胞系用编码本发明的人源化的或嵌合体的抗体的载体转化或转染。
本发明进一步提供了一种制备本发明的人源化或嵌合抗体的方法，其包括：
(i)提供用一个载体转化或转染的一种细胞，所述载体包括一种编码本发明的人源化或嵌合体抗体的核酸分子；
(ii)在有利于制造所述抗体的条件下使所述细胞增殖；以及
(iii)从所述细胞中或它的生长环境中纯化所述抗体。
本发明进一步提供了一种杂交瘤细胞系，其可产生如前所描述的单克隆抗体。
本发明进一步提供了一种用杂交瘤细胞系生产本发明的单克隆抗体的方法。
本发明进一步提供了制备一种能产生本发明的单克隆抗体的杂交瘤细胞系的一种方法，它包括以下步骤：
i)用一种免疫原免疫一种具有免疫活性的哺乳动物，所述免疫原包含至少一种具有如SEQ.ID No 14-19中所示的氨基酸序列的多肽或其片段；
ii)将接受免疫的免疫活性动物的淋巴细胞与骨髓瘤细胞融合形成杂交瘤细胞；
iii)根据与步骤(i)中的氨基酸序列的结合活性筛选出由步骤(ii)中的杂交瘤细胞产生的单克隆抗体；
iv)培养杂交瘤细胞以使其增殖和/或分泌所述单克隆抗体；以及
v)从培养上清液中回收单克隆抗体。
优选地，上述具免疫活性的哺乳动物是小鼠。或者，上述具免疫活性的哺乳动物是大鼠。
使用杂交瘤细胞产生单克隆抗体是本领域所熟知的。用于产生单克隆抗体的方法是由Kohler和Milstein，(自然256，495-497(1975))，和由Donillard和Hoffman(《免疫学概要》V.II中的“关于杂交的基本原理”，Schwartz编辑1981，该文献列入相关参考)公布的。
本发明进一步提供了应用抗体制造一种药物，以治疗金黄色葡萄球菌引起的败血症、食物中毒或皮肤损坏。
本发明进一步提供了应用本发明的抗体制造一种药物，以治疗表皮葡萄球菌引起的败血症、腹膜炎或心内膜炎。
显然，按照本发明的方法鉴定的多肽将促进治疗性抗体的生产，所述抗体能够用于一些由病原体感染引起的疾病，例如，败血症、结核病、细菌相关性食物中毒、血液感染、腹膜炎、心内膜炎、脓毒症、脑膜炎、肺炎、胃溃疡、淋病、链球菌喉炎、链球菌相关中毒性休克、坏死性筋膜炎、脓庖病，组织胞浆菌病、莱姆病、胃肠炎、痢疾、志贺菌病。
如前所述，病原微生物引起广泛的不同类型的疾病。例如但不限于下表所列的一些病原微生物及其引起的疾病。
| 微生物 | 引起的疾病 |
| 金黄色葡萄球菌 | 脓毒病，食物中毒，败血症 |
| 表皮葡萄球菌 | 腹膜炎，败血症，心内膜炎，其它医院-相关的疾病 |
| 粪肠球菌 | 心内膜炎，膀胱炎，外伤感染 |
| 结核分枝杆菌 | 结核病 |
| B族链球菌 | 脓毒病，脑膜炎，肺炎，膀胱感染 |
| 肺炎链球菌 | 肺炎，脑膜炎 |
| 幽门螺杆菌 | 胃溃疡 |
| 淋病奈瑟氏球菌 | 淋病 |
| A族链球菌 | 链球菌喉炎，坏死性筋膜炎，脓泡病，链球菌中毒休克综合症 |
| 布氏疏螺旋体 | 莱姆病 |
| 粗球孢菌 | 肺炎 |
| 荚膜组织胞浆菌 | 组织胞浆病，肺炎 |
| B型脑膜炎奈瑟氏球菌 | 脑膜炎 |
| 弗氏志贺氏菌 | 胃肠炎，志贺菌痢疾，痢疾 |
| 大肠杆菌 | 食物中毒，胃肠炎 |
| 流感嗜血菌 | 脑膜炎，肺炎，关节炎，蜂窝织炎 |
现仅举例说明本发明的一个实施方案并以下述材料、方法、SEQ IDNO：1-19和表1作为参考。
材料和方法
应用一种S.aureus 8325/4基因组DNA的λZAP表达文库。它包括从经过Sau3A部分消化的全部基因组DNA得到的2-10kb的片段。它被克隆进载体的BamH1位点。这个文库包括＞10倍基因组的范围。通过对在一个直径9厘米的Petri碟上的大约20,000个噬菌斑形成单位的初筛挑选噬菌斑对文库进行探测。铺皿所用的细胞，对细胞的处理，铺皿过程和缓冲液配制均严格参照制造商(Stratagene)提供的操作手册进行。铺皿细胞，大肠杆菌XL1-Blue MRF’，用噬菌体感染并放进3ml含有10mM硫酸镁的上层LB琼脂液中，铺在含10mM硫酸镁的LB平皿上。然后将平皿在42℃孵育4小时。将一个直径8.5厘米的纤维素滤膜片(之前浸泡在10mM的IPTG中并在空气中干燥)放在每个平皿上，并做出定位标志。然后将平皿进一步在37℃孵育3.5小时。将滤膜移去并用TBST缓冲液漂洗，然后在含有6％w/v脱脂奶粉和3％v/v猪血清(Sigma)的TBST中4℃下封闭过夜。血清是用于封闭滤膜上的所有蛋白A的克隆。滤膜然后用含有病人血清(1/5000稀释)的封闭液在室温下放置处理90分钟。抗血清从处于严重金黄色葡萄球菌感染的恢复期的病人中获得。滤膜然后在TBST中漂洗3次，每次10分钟。第二抗体用的是结合碱性磷酸酶的山羊抗人全IgG(Sigma)，1/30,000稀释于封闭液中室温孵育30分钟。滤膜然后按上述方法漂洗，并用标准比色法程序进一步处理。
有交叉反应的噬菌斑被定位在琼脂平皿上，被挑入0.2ml的含有0.02ml三氯甲烷的噬菌体缓冲液中。确定每个被挑入的噬菌斑的效价，然后每个平皿上大约接种200个噬菌斑。如上所述进行噬菌斑的挑选和筛选以得到单一的，纯的交叉反应克隆。
然后纯的克隆被接种(1μl)到平皿上，产生一个直径0.5厘米的汇合的噬菌斑。每块平皿上可接种30个单独的克隆。进行一次噬菌斑挑选，并用一种适当的血清对滤膜进行探测。这样能够检测克隆与其他病人的血清，未被感染的供体血清和抗蛋白A血清的交叉反应性。采用制造商的方案(Stratagene)将克隆切下以在XLOLR大肠杆菌中插入一个噬菌粒。进行一个质粒的小量制备，基因组插入的大小由限制性图谱决定。使用针对载体序列的引物，通过DNA测序对克隆插入进行鉴定，所述引物允许测序通过插入位点。通过将所获得得序列与公共结构域数据库进行比较，可确定所克隆的基因的性质。
杂交溶液/条件
典型地，杂交条件是用4-6倍的SSPE(20倍的SSPE含有175.3克NaCl，88.2克NaH2PO4H2O和7.4克的EDTA，溶解至1升，并且调节pH至7.4)；5-10倍的封闭溶液(50倍的封闭溶液含有5克400型的水溶性聚蔗糖，Pharmacia)，5克聚乙烯吡咯烷酮和5克牛血清白蛋白；100μg-1.0mg/ml超声处理的鲑鱼/鲱鱼精DNA；0.1-1.0％的十二烷基硫酸钠；任选地，40-60％去离子甲酰胺。杂交温度依核酸靶序列的GC含量的不同而变化，但典型地是介于42-65℃之间。
表1在人血清中识别金黄色葡萄球菌的克隆
| 病人血清 | 克隆 | 编码的蛋白 | 位点数目 |
| A | 1 | γ溶血素B和C亚基 | 1 |
| A | 3 | Atl | 2 |
| A | 4 | γ溶血素B和C亚基 | 1 |
| A | 5 | γ溶血素B和C亚基 | 1 |
| A | 7 | 新的推定的蛋白酶(ORF1新抗原类似物) | 7 |
| A | 8 | 新核酸酶(Yisk) | 5 |
| A | 9 | 新自溶素 | 6 |
| A | 10 | γ溶血素B和C亚基 | 1 |
| A | 11 | Atl | 2 |
| A | 14 | γ溶血素B和C亚基 | 1 |
| A | 15 | γ溶血素B和C亚基 | 1 |
| A | S1 | 新的推定的蛋白酶(ORF1新抗原类似物) | 7 |
| A | S5 | 新表面蛋白 | 12 |
| A | S17 | γ溶血素B和C亚基 | 1 |
| A | S18 | 新的推定的蛋白酶(ORF1新抗原类似物) | 7 |
| A | S19 | 新自溶素 | 6 |
| A | S20 | 新表面蛋白/毒素 | 13 |
| A | S21 | γ溶血素B和C亚基 | 1 |
| A | S25 | γ溶血素B和C亚基 | 1 |
| A | S29 | 血纤蛋白原结合蛋白 | 3 |
| A | S44 | 新表面蛋白 | 12 |
| A | S45 | Atl | 2 |
| A | S55 | Atl | 2 |
| A | S64 | Atl | 2 |
| A | S66 | Atl | 2 |
| B | 2 | 新外毒素(外毒素2类似物) | 8 |
| C | 1 | 凝固酶 | 4 |
| C | 2 | 凝固酶 | 4 |
| C | 3 | 凝固酶 | 4 |
| C | 4 | 凝固酶 | 4 |
| C | 5 | 凝固酶 | 4 |
| C | 6 | 凝固酶 | 4 |
| C | 7 | 凝固酶 | 4 |
| C | 8 | 凝固酶 | 4 |
| C | 9 | 凝固酶 | 4 |
| C | 10 | 凝固酶 | 4 |
| C | 11 | 凝固酶 | 4 |
| C | 13 | 凝固酶 | 4 |
| C | 14 | 凝固酶 | 4 |
| C | 15 | 凝固酶 | 4 |
| C | 19 | 凝固酶 | 4 |
| C | 20 | 凝固酶 | 4 |
| C | 25 | 凝固酶 | 4 |
| E | 6 | 新表面蛋白 | 9/10 |
| E | 7 | 新表面蛋白 | 9/10 |
| E | 11 | γ溶血素B和C亚基 | 1 |
| F | 1 | 新外毒素(外毒素2类似物) | 8 |
| F | 2 | 新外毒素(外毒素2类似物) | 8 |
| F | 3 | 新外毒素(外毒素2类似物) | 8 |
| F | 4 | 新外毒素(外毒素2类似物) | 8 |
| F | 5 | 新溶血素(YjfD) | 11 |
序列表
序列表<110>谢菲尔德大学<120>抗原多肽<130>toxin<140><141><160>32<170>PatentIn Ver.2.1<210>1<211>2260<212>DNA<213>Staphylococcus aureus<400>1gatcttaatg aaagagtgac tgatgcctta gcaattgcta gttgtatcaa tgcgcatccg 60tatgtcaaag gagaactttg cgtgtccgat gacttaacgt atacgacagg ttattttgcc 120gctgctaaaa ttggttacca tcgattattt gatattaaac cagttaatac gagatatgga 180ggcagaataa tatttgtgga cgattgtatt gatttaaatc attacatatc atttttagaa 240agcacaccga agcaagttgt ttatgaaacg gtataggggt tttagtatga catcaaaaga 300tattactcaa attagtgtca ttgctgcgat tttaaccatt ttggcagttt tgaaaatacc 360gtccattata ccaggattag attttcaatt atctgcaccg gcagcattat tgatattagc 420tttctttgga attaaaaagt actttttagg tggattatta tctagcctat tattactagt 480atttggcgta tttaatccaa ttaatgtgat tatctctatt atatttagag ttatagctat 540tgcagttgtt tatttattga aaataaatgt actatcatta gttttagcaa gtgtattagg 600cagtttggta tataggctac tattatctat tattttaaat ttacctgtgt gggtagtgtt 660gttaaacgcg attccaggcg taatattcac tttaattgta gctattcctt tatatctcac 720attgagaaaa agaatggcag tattactaag ataataaatc aaaacacggt cgtcacaatt 780actgttggcg accgtgtttt actagctatt tattgttttc agtttctttt gtatctaaca 840atttcacttt gtgattttcc caatcaattt catatgttga tttaaatgtt ctagttttaa 900agtttttata atttgcgcct gcccagtaga agccattcca acgaatttgg tataaatcca 960tttcacgttg ataagttact gtaattttag attttttagc gccatcttgt ctgtgtgata 1020gtacgcttaa aaattctgga ttgaagttac ttctagataa taatggcatt tggtgttgcg 1080ctatgaagtt ttggccagcg tatgcactgc tttgtctgcc agctaagaag agttcattac 1140catatgttgg gtggaagcta tctcttccat aaggtcccca accattattc ataattttat 1200gtgcttcaac tccccagcca acatttttat aatttgtgtt gcgacttaat gttgttctgt 1260aactttcttg tttataatta attgtttcag aaaaagctgt atttccatta agtccaccag 1320ataaaccatt agagatacta atgtcaccac caaatgtata gcctaaagta ttttgaactt 1380gaaactcttc attttgattt tttggtgcat aatcaacgac gtttactgaa tcattagatt 1440gtgagcttat agatacattg tatttagctc cccaatataa ttttgaaaag tcatagtcat 1500taggattagg tttcacaaag cctgagttaa tattcccagt agctttaagt actaaagtat 1560ctttatcata acttttatct ttgatgaaat taaatgttaa aatctgtgaa attttaaatt 1620tatcagaatc tgctgtggct gttgttttgt ataaagtaac tttgtcatcg acttttttta 1680cgctgactgg tgttatttta ccttcagcat tagcagtacc agaaagtaat aataatgcca 1740tagatgtagc aacggatgat ttgactaatt tattcatttt catatcaatt ctgtcctttc 1800accttgattt catgagtctt ccaattgacc tcgtatttca cagtatagtt tctatttaca 1860aatgcattat ggactctatg tccgtctaaa taactgttgc cataatgcgt tgatctttta 1920atggcatgag tgacatccat gtttcttccg taagtaattt caaattcgct tgtatcgctt 1980gaaccttttt catgagatac tgtggcgata aatgaagggt taaatccact ttgtacaaga 2040ggtggtaact cactgtctgg aacgaaataa tctctaggat ctttactatg aggtttgtag 2100cctacaaata aatcgctatc aaaggctgat ttttgacctg attcagtggc gaatgaattc 2160gctttgacgc cccataaaac actttttgag ttttgttgtt ctacttcact tacataattt 2220tgttgtgtat agctaatcga tttagaatag ttaaatgatc 2260<210>2<211>2902<212>DNA<213>Staphylococcus aureus<400>2gatcgtataa tcgaaacagc accaacggat tacttatctt ggggtgtcgg tgcagtcggt 60aaccctagat tcatcaatgt tgaaatcgta cacacacacg actatgcttc atttgcacgt 120tcaatgaata actatgctga ctatgcagct acacaattac aatattatgg tttaaaacca 180gacagtgctg agtatgatgg aaatggtaca gtatggactc actacgctgt aagtaaatat 240ttaggtggta ctgaccatgc cgatccacat ggatatttaa gaagtcataa ttatagttat 300gatcaattat atgacttaat taatgaaaaa tatttaataa aaatgggtaa agtggcgcca 360tggggtacgc aatctacaac tacccctact acaccatcaa aaccaacaac accgtcgaaa 420ccatcaactg gtaaattaac agttgctgca aacaatggtg tcgcacaaat caaaccaaca 480aatagtggtt tatatactac tgtatacgac aaaactggta aagcaactaa tgaagttcaa 540aaaacatttg ctgtatctaa aacagctaca ttaggtaatc aaaaattcta tcttgttcaa 600gattacaatt ctggtaataa atttggttgg gttaaagaag gcgatgtggt ttacaacaca 660gctaaatcac ctgtaaatgt aaatcaatca tattcaatca aacctggtac gaaactttat 720acagtacctt ggggtacatc taaacaagtt gctggtagtg tgtctggctc tggaaaccaa 780acatttaagg cttcaaagca acaacaaatt gataaatcaa tttatttata tggctctgtg 840aatggtaaat ctggttgggt aagtaaagca tatttagttg atactgctaa acctacgcct 900acaccaacac ctaagccatc aacacctaca acaaataata aattaacagt ttcatcatta 960aacggtgttg ctcaaattaa tgctaaaaac aatggcttat tcactacagt ttatgacaaa 1020actggtaagc caacgaaaga agttcaaaaa acatttgctg taacaaaaga agcaagttta 1080ggtggaaaca aattctactt agttaaagat tacaatagtc caactttaat tggttgggtt 1140aaacaaggtg acgttattta taacaatgca aaatcacctg taaatgtaat gcaaacatat 1200acagtaaaac caggcactaa attatattca gtaccttggg gcacttataa acaagaagct 1260ggtgcagttt ctggtacagg taaccaaact tttaaagcga ctaagcaaca acaaattgat 1320aaatctatct atttatttgg aactgtaaat ggtaaatctg gttgggtaag taaagcatat 1380ttagctgtac ctgctgcacc taaaaaagca gtagcacaac caaaaacagc tgtaaaagct 1440tatactgtta ctaaaccaca aacgactcaa acagttagca agattgctca agttaaacca 1500aacaacactg gtattcgtgc ttctgtttat gaaaaaacag cgaaaaacgg tgcgaaatat 1560gcagaccgta cgttctatgt aacaaaagag cgtgctcatg gtaatgaaac gtatgtatta 1620ttaaacaata caagccataa catcccatta ggttggttca atgtaaaaga cttaaatgtt 1680caaaacttag gcaaagaagt taaaacgact caaaaatata ctgttaataa atcaaataac 1740ggcttatcaa tggttccttg gggtactaaa aaccaagtca ttttaacagg caataacatt 1800gctcaaggta catttaatgc aacgaaacaa gtatctgtag gcaaagatgt ttatttatac 1860ggtactatta ataaccgcac tggttgggta aatgcaaaag atttaactgc accaactgct 1920gtgaaaccaa ctacatcagc tgccaaagat tataactaca cttatgtaat taaaaatggt 1980aatggttatt actatgtaac accaaattct gatacagcta aatactcatt aaaagcattt 2040aatgaacaac cattcgcagt tgttaaagaa caagtcatta atggacaaac ttggtactat 2100ggtaaattat ctaacggtaa attagcatgg attaaatcaa ctgatttagc taaagaatta 2160attaagtata atcaaacagg tatggcatta aaccaagttg ctcaaataca agctggttta 2220caatataaac cacaagtaca acgtgtacca ggtaagtgga caggtgctaa ctttaatgat 2280gttaagcatg caatggatac gaagcgttta gctcaagatc cagcattaaa atatcaattc 2340ttacgcttag accaaccaca aaatatttct attgataaaa ttaatcaatt cttaaaaggt 2400aaaggtgtat tagaaaacca aggtgctgca tttaacaaag ctgctcaaat gtatggcatt 2460aatgaagttt atcttatctc acatgcccta ttagaaacag gtaacggtac ttctcaatta 2520gcgaaaggtg cagatgtagt gaacaacaaa gttgtaacta actcaaacac gaaataccat 2580aacgtatttg gtattgctgc atatgataac gatcctttac gtgaaggtat taaatatgct 2640aaacaagctg gttgggacac agtatcaaaa gcaatcgttg gtggtgctaa attcatcggc 2700aactcatatg taaaagctgg tcaaaataca ctttacaaaa tgagatggaa tcctgcacat 2760ccaggaacac accaatatgc tacagatgta gattgggcta acatcaatgc taaaatcatc 2820aaaggctact atgataaaat tggcgaagtc ggcaaatact tcgacatccc acaatataaa 2880taagcaacat gaacatagga tc 2902<210>3<211>2792<212>DNA<213>Staphylococcus aureus<400>3gatcaactta atataatgaa ttcggcaaca gaagagcatc atcataaaga ttatattaaa 60ctatataatt taggtggcgg tgctgctaaa aaaattgcaa tagaggtttt attggggaag 120gataaagtca ttcagaaaaa atacgtgcat attttaccta gtaaagaagg gtacatgtta 180ccaattaata aaaatgtgta cgaagaatta gaaagaacga ttgagaacaa tggtcatgaa 240gctgatttga atgtacgtat gacttattat cataatgtaa gtcgcaaaca acaggaagtt 300atattaaaag gtcaaatcga ccgttttaat acttataata ataaagaaat ttatgatttg 360cagtttatct aaaaattgat ttaagagggt agttgtttat tgcgaaaaat atcattcaat 420tttaatgaaa taatggcgtc attactataa aatattactt tatgttgtaa tgcatttttc 480tataagatag aactaaaagg aggggcaaag atgcaaatta gacaaataca tcaacatgac 540tttgctcaag tggaccagtt aattagaacg gcatttgaaa atagtgaaca tggttatggt 600aatgaatcag agctagtaga ccaaattcgt ctaagtgata cgtatgacaa taccttagaa 660ttagtagctg ttcttcaaaa tgaagttgta gggcacggtt tactaagtga agtttatctt 720gataacgagg cacaacggga aattggatta gtgttagcac ctgtatctgt tgatattcat 780catcaaaata aaggtattgg gaagcgattg attcaagcat tagaacgaga agcaatatta 840aaaggatata attttatcag tgtattagga tggccgacgt attatgccaa tctaggatat 900caacgcgcaa gtatgtacga catttatcca ccatatgatg gtataccaga cgaagcgttt 960ttaattaaag aattaaaagt gaacagttta gcgggaaaaa caggtaccat aaattacaca 1020tctgcttttg aaaaaatatg atttcaagct aggattacat taggtagagt tcatattaat 1080aataaaaaat gtttgcaatc aaatcgtacg ttgtcgtttg taattcttaa aatagcaata 1140aataaaatgt ttgttagtaa agtattattg tggataataa aatatcgata caaattaatt 1200gctataatgc aattttagtg tataattcca ttaacagaga ttaaatatat ctttaaaggg 1260tatatagtta atataaaatg actttttaaa aagagggaat aaaatgaata tgaagaaaaa 1320agaaaaacac gcaattcgga aaaaatcgat tggcgtggct tcagtgcttg taggtacgtt 1380aatcggtttt ggactactca gcagtaaaga agcagatgca agtgaaaata gtgttacgca 1440atctgatagc gcaagtaacg aaagcaaaag taatgattca agtagcgtta gtgctgcacc 1500taaaacagac gacacaaacg tgagtgatac taaaacatcg tcaaacacta ataatggcga 1560aacgagtgtg gcgcaaaatc cagcacaaca ggaaacgaca caatcatcat caacaaatgc 1620aactacggaa gaaacgccgg taactggtga agctactact acgacaacga atcaagctaa 1680tacaccggca acaactcaat caagcaatac aaatgcggag gaattagtga atcaaacaag 1740taatgaaacg acttctaatg atactaatac agtatcatct gtaaattcac ctcaaaattc 1800tacaaatgcg gaaaatgttt caacaacgca agatacttca actgaagcaa caccttcaaa 1860caatgaatca gctccacaga gtacagatgc aagtaataaa gatgtagtta atcaagcggt 1920taatacaagt gcgcctagaa tgagagcatt tagtttagcg gcagtagctg cagatgcacc 1980ggcagctggc acagatatta cgaatcagtt gacgaatgtg acagttggta ttgactctgg 2040tacgactgtg tatccgcacc aagcaggtta tgtcaaactg aattatggtt tttcagtgcc 2100taattctgct gttaaaggtg acacattcaa aataactgta cctaaagaat taaacttaaa 2160tggtgtaact tcaactgcta aagtgccacc aattatggct ggagatcaag tattggcaaa 2220tggtgtaatc gatagtgatg gtaatgttat ttatacattt acagactatg taaatactaa 2280agatgatgta aaagcaactt tgaccatgcc cgcttatatt gaccctgaaa atgttaaaaa 2340gacaggtaat gtgacattgg ctactggcat aggtagtaca acagcaaaca aaacagtatt 2400agtagattat gaaaaatatg gtaagtttta taacttatct attaaaggta caattgacca 2460aatcgataaa acaaataata cgtatcgtca gacaatttat gtcaatccaa gtggagataa 2520cgttattgcg ccggttttaa caggtaattt aaaaccaaat acggatagta atgcattaat 2580agatcagcaa aatacaagta ttaaagtata taaagtagat aatgcagctg atttatctga 2640aagttacttt gtgaatccag aaaactttga ggatgtcact aatagtgtga atattacatt 2700cccaaatcca aatcaatata aagtagagtt taatacgcct gatgatcaaa ttacaacacc 2760gtatatagta gttgttaatg gtcatattga tc 2792<210>4<211>2478<212>DNA<213>Staphylococcus aureus<400>4gatcgaattg aacgaagcat ttgcttctca aacgattgca tctattaaag aagtaggtct 60agatatatca cgtacgaatg tgaatggtgg cgctattgct ttaggtcatc cattaggtgc 120tacaggcgca atgttaaccg cgcgtttact taatgaaatg ggtagacgtc ccgatagccg 180ttacggcatg gttacgatgt gtattggtgt cggcatgggt gcagctgcta tatttgaata 240tgtgcgttag aatggttgat tttggatgaa gcggattcgt tttgttattg aatgaagtag 300gctgaagttg aagccagttg aagttgaagc gggttgaagc aatttcgttt tattaatgaa 360gctgtgtgaa atatagtgat tgaacaaaaa agtggtttaa tgggatggtg gttatttccg 420ttttagaatt taacatttac acgtctaatt ttaatcattg ttttaaattt tatgaatcga 480agccctttga tttaataata tttgctaatg ctagtaactt atctgattgt tcatgtttaa 540aataaagaaa accactcaca tcagtgtgtg ttcgaactag acttgtaagt tccagttcgg 600cacgactttc taaagcaatt attattgctg tgattgtcgt atatcactta gatgtgcgtg 660gtttatttta ataggttagt aatatattag gtcatgttat gtttaagact ataatgaata 720aataatttag aaatatgctt ccgattgttc gatgctttaa ttcagttaga agcatcatag 780aatgcatgat tactgttgta aagatacgta atgttttgta ttgactgtat gtctttggat 840agagttacaa acttattttg ttactctagg cccatatgtc gcagtaccat ctgcatgtgt 900tgttacattg tatgcatttg ttttacttgg cttcttgtat gtcgggcgag ctccgtatga 960cacttgaccg tttgcatgtg ttgttacgtt gtatgcattt gttttgcttg gcttgttttg 1020tgttgggcga gcgccatatg atacttggcc gtttccatgt gttgttacgt tatatgcgtt 1080tgttttgctt ggcttgtttt gtgtcggacg agctccgtat gatacttggc cgtttgcatg 1140tgttgttaca ttgtatgcat tcgtttcgct tggcttcttg tatgtcggac gagctccgta 1200tgatacttga ccatttgcat gtgttgttac gttatatgca tttgtttctg atggcttatt 1260gaatcttggt ctcgcttcat atccaaatgt tccatcgttg tattcacgga tacctgtacc 1320agcatctcta tatttaacat atttaggtgt tttgttaaat tgcggtctcg gaccatattg 1380agaagcttct gttgtttcag ttgcttgagg tttaacttca atatcacttg attctccttg 1440agtacctttt aacgttgatt cagtaccttg tggttttatt tcaagtttag atgagctacc 1500ttcaagacct tctaaaatag ggttcgttaa cggtgggttt gtataattat tgcttaatga 1560tgggccgctt tgttccattg ttagaaaatc gggaccttga acgatttcac cttgtaccgt 1620tttattttcc atcgttggat attccggacc ttttacaatt tcacctgtaa ttgtgccctg 1680tggaatttta actaatggtt gtgcaactgg ttgtgttgtt tcttcagctt taccagccgt 1740agttttaacc tcttgttggt tatcaacttt aggtgcttga ggttcttcaa ctttcttctc 1800ttcttttact actggcgatt ttgtttcagt ttctccgtat tttttgacag ttttcttttt 1860ccaagaatca tctgcttctt taactgcttt tttcgtttct tcaactaatt tatcaaaatt 1920aggtttatta tcactatttg ttttatagtt atgtgttgta ggattatatt tcgttataga 1980tttcggtcta ttttgtttag tttccataaa gaaatcatca ataattgaat ttaagtcatc 2040aatcatttct tttttaatac gttcatttgt aattttatgt ggattgtctg tatctccaag 2100gattaagtcc agttttgctc gtaactcttt cgcgtgctcc ccataatcct tatcaccata 2160atatgataca actaatgtat caatttcaga tacgagatcg tatacttcct tagttgcttt 2220atcttcttct gctgcattaa aagttttcaa gtctgaattc ttatccttaa tatctttaac 2280ttctctgtga aaatcatcca gtgctctctt taatgcatcc tgtagttcat tgtattcttt 2340catcgaaagt tcttctaaat tatatttatg aaaattagcc atttttaaat ctgtacgagg 2400attttctttt ttataatttg cataccattg tttataatct tcatattgag atttctttct 2460ctccaaaaga tattgatc 2478<210>5<211>2070<212>DNA<213>Staphylococcus aureus<400>5tgacgctgct tttgtaaata catataattt ttccacttca tgatttaatt cgttcgcatg 60atctttgtaa tttctaccaa aagcaatcac attattcgga ggtgttactg gtggtaaaaa 120ttcaatgtca ttaaatgaaa ttttatagtc ttcagctttg ccgctatctt ctgctgctac 180aactgcttta cgtacttgtt cttgaaaatc taaagtatga ttttgttgta aaccagctaa 240caatgtttta ggatggaaat ctccttctgc aaagtcagca aatacttgtg ttaaatccca 300tacagcatct tcgcgtttta ctttaacgcc atatgaagtt ttgtcattat acttgaatga 360taagaatttc attcattctc aactcctcgt ctttatctta attcacatta taactttttt 420cgttatcaaa taacaaataa ataagtaaga caattttgaa aatgagttgt gttcattctg 480ctacaaggac tttgcactta atcgaaatta ttttttattc ttttgaaaat caaaatacta 540tagttgcaat gtaccaaatt tgaagaagta taaataacct ttaacttctt tattaagaat 600cgtttgaagc gtattttgat aatatttcat ctgtatctta tatttatttt ttaattgtgt 660accaatttct tcatctgtca tcccacggcg acgattaaat gcatcggttt tatagtctac 720aaaataatgc acaccatctt taacaaagat taagtcaatc ataccttgaa taattgagac 780gtcttcgtct ccttgtggca attggtcaac taatgcttgg ttaactacaa acggtaattc 840acgataaact tgctctgctt cagcaataat cgaatataac tcactattga taaatgtcat 900tatttcatcc atacggatat cttttttcgc atctgcttcg ataatatgtt tatcgattaa 960tccatcgata tactgatgta actcaacttc agatatgcgt tcttttttga atggtaaatg 1020ttgcatcact gtatgcatta acgtaccaat ttcattcgct tttcgtttac cttgttcact 1080tagaaattta ggtcgttcat acgttgaaaa accgatacga tattgcctta ctcgttcgta 1140acttgtgcca ctttcttctg tttcatattg tcttttcaat tcagaaacag attgttttga 1200gggcttttta gtatcattta catatggata tcgataatca agttggtgtt taatttgtgc 1260tttaacatct tcattaccat tttgcatagt ttctaattga ttaaccgaac gatattcatc 1320attatctaaa atggtttctg tagacacatc ttcaaagtac acaattgaaa tatttacatt 1380cggacgacta ctatcttcaa tttgtgctat atctttttca aattttaaat catctggaat 1440tgacgcagat tgatgtttag ataaaatact ataaataaga tggaacggat ttggtgaagt 1500taatcgttca ttgacagcaa tgtgctcacc agaaatagac aattgctcta gttctagtaa 1560tgatttatca tttttcactc taccaattaa ataaagttgt tctttcgctc ttgttaatgc 1620tacatagact aatcgcattt cttctgacac aagttctttt tcggcaacag ctctatatgc 1680aaccgaagct aaagatggaa atgccatttc tttatccaca tcaaaataat ccattccgag 1740accaaattgc tgatttaaaa taactggttg tttcaaatca cgtttattaa aatcttttga 1800caatccagaa taaatgacaa atggaaactc tagaccttta ctactatgaa ttgtcatcat 1860tctaacgaca ttatcgtttg gaccaactac attttcctca ccaaaatctt tgcctctttc 1920aatcaattca tcgataaaac gaataaattg atataaacct ctaaaacttg aattctcaaa 1980ctcgatagct ttattaaata aaccataaag atttgcacgt cgtccacgtc caccaataag 2040tccactaaag tattgaataa cataatgatc 2070<210>6<211>2394<212>DNA<213>Staphylococcus aureus<400>6gatcagattt attagacagt attccagata tacccacacc aaagccagaa aagacgttaa 60cacttggtaa aggtaatgga ttgttaagtg gattattaaa tgctgatggt aatgtatctt 120tgcctaaagc gggggaaacg ataaaagaac attggttgcc gatatctgta attgttggtg 180caatgggtgt actaatgatt tggttatcac gacgcaataa gttgaaaaat aaagcataat 240tatattgggg gaagagcatc tatatatttt tttaagtata taagacgtct tatttcccct 300taatttattg tgaagtatat gcaaaatgca atgaatagat tgtccatcat tttaacgtta 360taatgaattt aacgacttag aactacacaa gtaaaggaga atgaagatgt ctcgaaaaac 420ggcgctatta gttttggata tgcaagaagg tatagcgagt agtgtaccta gaataaaaaa 480tattattaaa gcgaatcaga gagcaattga agcagcaaga caacatcgaa taccagtcat 540tttcatacgt ttagtgttag ataagcattt taatgatgtc tcctcgagta ataaagtgtt 600ttcaacaatt aaagctcaag gatatgcgat tactgaagca gatgcatcta cacgaatact 660tgaagattta gcaccactag aagatgagcc gattatttct aagcgacgct ttagcgcatt 720tacaggtagt tacttggaag tttatttacg tgcaaatgat attaatcatt tagtattaac 780gggtgtctct acaagtggag ctgtattgag cacggcatta gaaagtgtag ataaagacta 840ttatattact gttttagaag atgctgttgg tgatagatca gatgataaac atgactttat 900tattgaacaa attttatcac gctcatgtga cattgaatcc gtagagtcat ggaaaagtag 960tttatagtta atataacgtc aattaaagct cggcagtaat gtttgagaat aagtacattt 1020gctcatattt ataaaatgtg tgagatggca attgaaacgg atatgatgag gaacatttga 1080acataaaata atatatttat ataaaacgac ccgaggcgtt cgaactgaat gcctcgggtt 1140taattgaata agaaatcgga cttatgaaca gaaatatgtt taagtccgaa ctccttgttt 1200atacttataa attttacggg tttaatataa tacttattta cctgtaatat atgataattc 1260ttcagcggca gctgcgttga tagttctatg agaaatgata cctaatcctt taacattgga 1320ttctgaaata acgatagaac catcactgtt aactttttca acaaatgcta catgaccgta 1380atgttgatct gcaccaaatt gtccagcctc aaatacaaca gcagcatgac gttttggtgt 1440atgacttact tgataatcac ggtattgagc tcgattattc caattatgtg catcacctaa 1500atcacctgag atagatgtac caaattgttt catacggtta tatacgtacc aagtacattg 1560gccatgtgga tatggcatac tatcagatac ctcacggaaa ggtttgaatt catctgatga 1620atcatcataa tccttgatag aacgttcata tttatctaaa tctggcatgc gttcatcgtc 1680aaactgagtt aattgatagt gtttaataat actgtttaat ttcttagcat agtttggatc 1740tgtagcatat gttttagata agtgtgatgt tgcatcttta taagaatcgg cttccgattt 1800ccatgttggt ttataaattg ttcgattgcc atcaatacca tttttaataa ggtcagagta 1860atcttttagt gattctttcg tgcttggata ttttcggaat ccagcattaa tactatacaa 1920ttgattacca tcagcttcta atgtgttaaa aggaacagaa ttcccttcaa aagcaccttt 1980gataccgaat aaattatggt ttggtgactt agctaaagca ctacgacctg agtcagattc 2040taagattgct tgggcaatca tgacagacgc ataaatatcg ttatcttgac caatgcgatg 2100tgcatcttta gcaattgatt tgacaaattg acgtgtatct tttgagtcaa caacgttaaa 2160ttgtccgcta tcatcattgt tagatatact aggatctgtt tcgaataatg atgttgcacg 2220tgtatccttt tgattaacat cgttattgaa tgattgagca ggtttagatt tatgtttcaa 2280ttcatcttgt gttggtaact gtggattctt tgtattagat ttttcatttt tgtctttttt 2340agattgagat gcataatctt tttgtgtttt ctttgcatct tcactgtatt gatc 2394<210>7<211>2033<212>DNA<213>Staphylococcus aureus<400>7gatctggaac aggtttcatt gtcggtaaaa atacaattgt taccaacaag catgtcgttg 60caggtatgga aattggtgca catattatag cgcatcccaa tggtgaatat aataatggcg 120gattttataa agttaaaaaa attgtccgtt attcaggtca agaagatatt gccattctac 180atgtggaaga taaagctgtt catccaaaaa acaggaattt taaagattac acaggcattt 240taaaaatagc atcagaagct aaagaaaatg aacgcatttc aattgttggc tatccagaac 300catatataaa taaatttcaa atgtatgagt caacaggaaa agtgctgtca gttaaaggca 360acatgattat tactgatgct ttcgtagaac caggcaactc aggttcagct gtatttaaca 420gtaaatacga agttgtaggt gttcactttg gtggaaacgg ccctggaaat aaaagtacaa 480aaggatatgg tgtttatttc tctcctgaaa ttaagaaatt cattgcagat aacacagata 540aataaatcct tacatagata aatgatttta aaaattaaca acaaactcaa caattcaaat 600catctctgtg attccattta ttcgaaatga ttaaaaaaaa taaaacttca aaaagctaac 660attataatta tacaaatact tagaggagca gaaaaatgaa taaaaatata atcatcaaaa 720gtattgcagc attgacgatt ttaacatcaa taactggtgt cggcacaaca atggttgaag 780gtattcaaca aacagccaaa gccgaaaata ctgttaaaca aattacaaat acaaatgttg 840caccatacag tggtgttaca tggatgggcg ctggaacagg atttgtagtt ggaaatcata 900caatcattac caataaacat gttacctatc acatgaaagt cggtgatgaa atcaaagcac 960atcctaatgg tttttataat aacggtggtg gactttataa agttactaag attgtagatt 1020atcctggtaa agaagatatt gcggttgtac aagttgaaga aaaatcaaca caaccaaaag 1080gtagaaaatt caaagatttc actagtaaat ttaatatagc atcagaagct aaagaaaatg 1140aacctatatc agtcattggt tatccaaatc ctaatggaaa taaactacaa atgtatgaat 1200caactggtaa agtattatca gtgaatggga atatagtgtc ttcggatgca attattcagc 1260ctggtagctc tggttcacct atattaaata gtaaacacga agctattggt gtaatctatg 1320ccggtaataa gccatcaggt gaaagcacaa gaggatttgc tgtttatttc tctcctgaaa 1380ttaagaaatt cattgcagat aatttagata aataattaaa acttagacat tcacccaatc 1440ctgacaaaat atactataac taacatttat taatatatat tgcattattt aatatgcatc 1500aaagccaatc aacgattgat tttcaccaac tcaattgttg attggtttta tttatgtatg 1560aatgaacaac tttttgacat cattaagaat ataaatgatt ttgaaagcat ttgaaagcta 1620caacatttct ataaaatttt tcaataacaa ttgcgccact aaaactcaaa atttccacca 1680ccaacatcca aattatcaac atcgcaacat aaccaaatgt tataataaat ctattacaca 1740aagagataaa ttacttatgc aaaggcggag gaatcacatg tctattactg aaaaacaacg 1800tcagcaacaa gctgaattac ataaaaaatt atggtcgatt gcgaatgatt taagagggaa 1860catggatgcg agtgaattcc gtaattacat tttaggcttg attttctatc gcttcttatc 1920tgaaaaagcc gaacaagaat atgcagatgc cttgtcaggt gaagacatca cgtatcaaga 1980agcatgggca gatgaagaat atcgtgaaga cttaaaagca gaattaattg atc 2033<210>8<211>2794<212>DNA<213>Staphylococcus aureus<400>8gatcaaacgt tgcttaactt ctttttaatg cttaaaaatt atttcaaagg cacatagaaa 60cgctatatta atctcatact cactcattat tttttgctta aattacttaa taatacttca 120ataattgtta aaaggggttt aatgtgatta tcttagaacg ccatctataa tgatgttgta 180tgattcaaat tacgtaaaaa gacaatcgaa tataatatag attggagcat acaattatga 240aaatgagaac aattgctaaa accagtttag cactagggct tttaacaaca ggcgcaatta 300cagtaacgac gcaatcggtc aaagcagaaa aaatacaatc aactaaagtt gacaaagtac 360caacgcttaa agcagagcga ttagcaatga taaacataac agcaggtgca aattcagcga 420caacacaagc agctaacaca agacaagaac gcacgcctaa actcgaaaag gcaccaaata 480ctaatgagga aaaaacctca gcttccaaaa tagaaaaaat atcacaacct aaacaagaag 540agcagaaaac gcttaatata tcagcaacgc cagcgcctaa acaagaacaa tcacaaacga 600caaccgaatc cacaacgccg aaaactaaag tgacaacacc tccatcaaca aacacgccac 660aaccaatgca atctactaaa tcagacacac cacaatctcc aaccataaaa caagcacaaa 720cagatatgac tcctaaatat gaagatttaa gagcgtatta tacaaaaccg agttttgaat 780ttgaaaagca gtttggattt atgctcaaac catggacgac ggttaggttt atgaatgtta 840ttccaaatag gttcatctat aaaatagctt tagttggaaa agatgagaaa aaatataaag 900atggacctta cgataatatc gatgtattta tcgttttaga agacaataaa tatcaattga 960aaaaatattc tgtcggtggc atcacgaaga ctaatagtaa aaaagttaat cacaaagtag 1020aattaagcat tactaaaaaa gataatcaag gtatgatttc acgcgatgtt tcagaataca 1080tgattactaa ggaagagatt tccttgaaag agcttgattt taaattgaga aaacaactta 1140ttgaaaaaca taatctttac ggtaacatgg gttcaggaac aatcgttatt aaaatgaaaa 1200acggtgggaa atatacgttt gaattacaca aaaaactgca agagcatcgt atggcagacg 1260tcatagatgg cactaatatt gataacattg aagtgaatat aaaataatca tgacattctc 1320taaatagaag ctgtcatcgg aaaaacaaga agttaagtga caacggttta catgttgctt 1380agcttctttt attatgcgta atgatgtaaa aagacgaata ttcatttgtt tgtaaaagtg 1440gcatttctat gtcttaaaag tgacgaaact tcaaatgtgc caagtgttga atcacatcaa 1500aatcattttt atttaacgaa cattatggat ttcttaattt acttaacgat gattcaaata 1560tagttaaaca aggtttaatg tgaatggagc aatacgccat ctataataaa gctgtatgat 1620tcaatgaatg taatcgaaca aatctaataa ttacgaatgg agcatacaac tatgaaaata 1680acaacgattg ctaaaacaag tttagcacta ggccttttaa caacaggtgt aatcacaacg 1740acaacgcaag cagcaaacgc gacaacacta tcttccacta aagtggaagc accacaatca 1800acaccgccct caactaaaat agaagcaccg caatcaaaac caaacgcgac aacaccgccc 1860tcaactaaag tagaagcacc gcaacaaaca gcaaatgcga caacaccgcc ttcaactaaa 1920gtgacaacac ctccatcaac aaacacgcca caaccaatgc aatctactaa atcagacaca 1980ccacaatcgc caaccacaaa acaagtacca acagaaataa atcctaaatt taaagattta 2040agagcgtatt atacgaaacc aagtttagaa tttaaaaatg agattggtat tattttaaaa 2100aaatggacga caataagatt tatgaatgtt gtcccagatt atttcatata taaaattgct 2160ttagttggta aagatgataa aaaatatggt gaaggagtac ataggaatgt cgatgtattt 2220gtcgttttag aagaaaataa ttacaatctg gaaaaatatt ctgtcggtgg tatcacaaag 2280agtaatagta aaaaagttga tcacaaagca ggagtaagaa ttactaagga agataataaa 2340ggtacaatct ctcatgatgt ttcagaattc aagattacta aagaacagat ttccttgaaa 2400gaacttgatt ttaaattgag aaaacaactt attgaaaaaa ataatctgta cggtaacgtt 2460ggttcaggta aaattgttat taaaatgaaa aacggtggaa agtacacgtt tgaattgcac 2520aaaaaattac aagaaaatcg catggcagat gtcatagatg gcactaatat tgataacatt 2580gaagtgaata taaaataatc atgacattct ctaaatagaa gctgtcatcg gaaaaacaag 2640aagttaagtg acaacggcct acatgttgct tagcttcttt tgttatgttc gatgatttga 2700gaacccgaat tttcgatggg tccaaatatg acgtggaaga gacctgaatt tatctgtaaa 2760tccctatcta tcgggtgtga agcacaacgg gatc 2794<210>9<211>505<212>DNA<213>Staphylococcus aureus<400>9gatcatagcg caccaaactc tcgtccaatt gattttgaaa tgaaaaagaa agatggaact 60caacagtttt atcattatgc aagttctgtt aaacctgcta gagttatttt cactgattca 120aaaccagaaa ttgaattagg attacaatca ggtcaatttt ggagaaaatt tgaagtttat 180gaaggtgaca aaaagttgcc aattaaatta gtatcatacg atactgttaa agattatgct 240tacattcgct tctctgtatc aaacggaaca aaagctgtta aaattgttag ttcaacacac 300ttcaataaca aagaagaaaa atacgattac acattaatgg aattcgcaca accaatttat 360aacagtgcag ataaattcaa aactgaagaa gattataaag ctgaaaaatt attagcgcca 420tataaaaaag cgaaaacact agaaagacaa gtttatgaat taaataaaat tcaagataaa 480cttcctgaaa aattaaaggc tgagt 505<210>10<211>673<212>DNA<213>Staphylococcus aureus<400>10gatcaaacta aaacacaaac tgctcataca gttaaaacag cacaaactgc tcaagaacaa 60aataaagttc aaacacctgt taaagatgtt gcaacagcga aatctgaaag caacaatcaa 120gctgtaagtg ataataaatc acaacaaact aacaaagtta caaaacataa cgaaacgcct 180aaacaagcat ctaaagctaa agaattacca aaaactggtt taacttcagt tgataacttt 240attagcacag ttgccttcgc aacacttgcc cttttaggtt cattatcttt attacttttc 300aaaagaaaag aatctaaata aatcatcgtc acactcataa cttaatatat tttttatttt 360aaattttatt taacctatgt catagatatt tcataatcta taacataggt tatttttttt 420ataaaataac gttgcaatta actaacattt caatgtcaat acaagtaatc aattgataat 480gattatcagt tgataatata caattaggag ttgtttctac aacatgaaca aacagcaaaa 540agaatttaaa tcattttatt caattagaaa gtcatcacta ggcgtgcatc tgtagcaatt 600agtacacttt tattattaat gtcaaatggc gaagcacaag ccagcagctt gaagaaaaca 660ggtggtccaa ttc 673<210>11<211>2238<212>DNA<213>Staphylococcus aureus<400>11gatcttcagc ttgatgtttt cgtttgatta aattggtaaa atagaaacgc aatccacaaa 60aatggcaagc actaaaataa tgtttggggg tgcttgtgct tttgtggatt gcggtcgatt 120atttatattg catgatttga ttaatttgat tgattatatt ggacatgatg gtgttggcgg 180gatgcgttgt tgctagtcgc gggctttgtc cactccacat atgtattaac tctttgtcgc 240cgatgtttgc tgcggctttt cttatgctac ttgttagctc attttgtatt ggataatctg 300ggatatcgcc ttcgtattgg gacatttctt cgataaacct attgttgata ccgcgtgcaa 360gctttccact aaacgctttt gtaatgactg tatctgtttc tttactattt ataattgcat 420ctcgcagtag ttctgatgca ttactgtctt gtgatgttaa aaatgcggtg cccatttgta 480ccccttctgc acctaagaca atacttgcca aaactcctct accatccata attccaccag 540cggcaatgac cggaattgaa acgacatcta caatttgtgg cactaaagat attgttccaa 600ccataggtaa ttgattttta ggttttaaaa atgaaccacg atgtccacct gcttcactac 660cttgagcaac gatagcatcc atacccgctt tttcattcgc aatagcttca tcaacacttg 720ttgctgtacc tataagtttg acattcgctg ctttcaacct gcttataatc tgttcgcttg 780gaattccaaa agtaaaacaa catacaggca cttgcttttt aattatcgta tcaatatgac 840acttaaattg ttgttcttcg gtaattttta caaccggctc ttctaaatgt aatgcgcgtc 900gataaggttt taaccatgca ttcatatttt caatttgact actggtatat gattgttgac 960ttggtacaaa gacatttacg ccaaaagaat ttgacgttaa ttggcgtaca taatctattt 1020catcttccaa ttgctgcgta ttaaagtaac ctgcgcctat tgtgcctaac ccaccactgt 1080tacttactga tgcaactaat ttcggtgtcg tacttcctgc catacctgct tgtataattg 1140gatattcaat acttaacatt tgagtaagtc gattcttatt ccacatagct gttcgctcct 1200tatatagata cgttgcgatt tttccgttgt tgaaattgaa tttgctgttg agaaagtttt 1260tctttttcct ttttatccat ctcatcttca atttccatac ctaataattc ttcaattaag 1320tcttcatgtg acactatcgc ttcagtacca ccaaattcgt ccaacacaat tgctaaatgt 1380tttctagaaa tagtcatctt acgtaatacc cattcagctt tattgtgttc attcacaaat 1440aatggcttag ctgaatagtt tgtaatttga ttttcttttt tattactcca agccaacaga 1500tatttagaat gaaacacccc aataatgtta tcaatatctc cctcgtacac tggatatcta 1560gtgtatggct tattcataac cgtttcataa acttcttcgt atgtcgcatt tgaagcaaat 1620gccgtcacat taattctagg tgttgtatct acatctttta cttttaaatt ttcaaaatta 1680atgacacctt ccaacctact cgtctcaatt tcatttaaag caccttcatg tccagcaatt 1740gctaacattg ttttaaattc ttcttttgaa aattgatgtt cttgaggttg gcccttagat 1800aaacttcgat taatactgtc cgtcaactta tttaaaagta atgtgatagg acggaacaca 1860atgacacaaa tattaataat tggatataca agccttgtta ttttatctgg aaatgttgca 1920gcgacagact tgggaatcac ttcggagatc aaaatgataa caactgttaa aacagctgat 1980gcaataccaa cgctaatccc ccaacgtaaa gccataattg taacaagtgt tggtaataaa 2040atattcgcga cattattccc aattagaatc gttgtaataa actcacttgg tttttcaagt 2100aactttacaa tgccttttgc ttttttatca cctttgtcag cttcagtttt aaattttgct 2160ttattggcag ccgttaatgc cgtctcgctt cctgaaaaga aaaacgaaat aaatatcaat 2220ataattatgg caatgatc 2238<210>12<211>7975<212>DNA<213>Staphylococcus aureus<400>12gatcaaacga caattattaa ttcgttaacg tttactgaaa cagtaccaaa tagaagttat 60gcaagagcaa gtgcgaatga aatcactagt aaaacagtta gtaatgtcag tcgtactgga 120aataatgcca atgtcacagt aactgttact tatcaagatg gaacaacatc aacagtgact 180gtacctgtaa agcatgtcat tccagaaatc gttgcacatt cgcattacac tgtacaaggc 240caagacttcc cagcaggtaa tggttctagt gcatcagatt actttaagtt atctaatggt 300agtgacattg cagatgcaac tattacatgg gtaagtggac aagcgccaaa taaagataat 360acacgtattg gtgaagatat aactgtaact gcacatatct taattgatgg cgaaacaacg 420ccgattacga aaacagcaac atataaagta gtaagaactg taccgaaaca tgtctttgaa 480acagccagag gtgttttata cccaggtgtt tcagatatgt atgatgcgaa acaatatgtt 540aagccagtaa ataattcttg gtcgacaaat gcgcaacata tgaatttcca atttgttgga 600acatatggtc ctaacaaaga tgttgtaggc atatctactc gtcttattag agtgacatat 660gataatagac aaacagaaga tttaactatt ttatctaaag ttaaacctga cccacctaga 720attgacgcaa actctgtgac atataaagca ggtcttacaa accaagaaat taaagttaat 780aacgtattaa ataactcgtc agtaaaatta tttaaagcag ataatacacc attaaatgtc 840acaaatatta ctcatggtag cggttttagt tcggttgtga cagtaagtga cgcgttacca 900aatggcggaa ttaaagcaaa atcttcaatt tcaatgaaca atgtgacgta tacgacgcaa 960gacgaacatg gtcaagttgt tacagtaaca agaaatgaat ctgttgattc aaatgacagt 1020gcaacagtaa cagtgacacc acaattacaa gcaactactg aaggcgctgt atttattaaa 1080ggtggcgacg gttttgattt cggacacgta gaaagattta ttcaaaaccc gccacatggg 1140gcaacggttg catggcatga tagtccagat acatggaaga atacagtcgg taacactcat 1200aaaactgcgg ttgtaacatt acctaatggt caaggtacgc gtaatgttga agttccagtc 1260aaagtttatc cagttgctaa tgcaaaggcg ccatcacgtg atgtgaaagg tcaaaatttg 1320actaatggaa cggatgcgat gaactacatt acatttgatc caaatacaaa cacaaatggt 1380atcactgcag catgggcaaa tagacaacaa ccaaataacc aacaagcagg cgtgcaacat 1440ttaaatgtcg atgtcacata tccaggtatt tcagctgcta aacgagttcc tgttactgtt 1500aatgtatatc aatttgaatt ccctcaaact acttatacga caacggttgg aggcacttta 1560gcaagtggta cgcaagcatc aggatatgca catatgcaaa atgctactgg tttaccaaca 1620gatggattta cgtataaatg gaatcgtgat actacaggta caaatgacgc aaactggtca 1680gctatgaata aaccgaatgt ggctaaagtc gttaacgcaa aatatgacgt catctataac 1740ggacatactt ttgcaacatc tttaccagcg aaatttgtag taaaagatgt gcaaccagcg 1800aaaccaactg tgactgaaac agcggcagga gcgattacaa ttgcacctgg agcaaaccaa 1860acagtgaata cacatgccgg taacgtaacg acatacgctg ataaattagt tattaaacgt 1920aatggtaacg ttgtgacgac atttacacgt cgcaataata cgagtccatg ggtgaaagaa 1980gcatctgcag caactgtagc aggtattgct ggaactaata atggtattac tgttgcagca 2040ggtactttca accctgctga tacaattcaa gttgttgcaa cgcaaggaag cggagagaca 2100gtgagtgatg agcaacgtag tgatgatttc acagttgtcg caccacaacc gaaccaagcg 2160actactaaga tttggcaaaa tggtcatatt gatatcacgc ctaataatcc atcaggacat 2220ttaattaatc caactcaagc aatggatatt gcttacactg aaaaagtggg taatggtgca 2280gaacatagta agacaattaa tgttgttcgt ggtcaaaata atcaatggac aattgcgaat 2340aagcctgact atgtaacgtt agatgcacaa actggtaaag tgacgttcaa tgccaatact 2400ataaaaccaa attcatcaat cacaattact ccgaaagcag gtacaggtca ctcagtaagt 2460agtaatccaa gtacattaac tgcaccggca gctcatactg tcaacacaac tgaaattgtg 2520aaagattatg gttcaaatgt aacagcagct gaaattaaca atgcagttca agttgctaat 2580aaacgtactg caacgattaa aaatggcaca gcaatgccta ctaatttagc tggtggtagc 2640acaacgacga ttcctgtgac agtaacttac aatgatggta gtactgaaga agtacaagag 2700tccattttca caaaagcgga taaacgtgag ttaatcacag ctaaaaatca tttagatgat 2760ccagtaagca ctgaaggtaa aaagccaggt acaattacgc agtacaataa tgcaatgcat 2820aatgcgcaac aacaaatcaa tactgcgaaa acagaagcac aacaagtgat taataatgag 2880cgtgcaacac cacaacaagt ttctgacgca ctaactaaag ttcgtgcagc acaaactaag 2940attgatcaag ctaaagcatt acttcaaaat aaagaagata atagccaatt agtaacgtct 3000aaaaataact tacaaagttc tgtgaaccaa gtaccatcaa ctgctggtat gacgcaacaa 3060agtattgata actataatgc gaagaagcgt gaagcagaaa ctgaaataac tgcagctcaa 3120cgtgttattg acaatggcga tgcaactgca caacaaattt cagatgaaaa acatcgtgtc 3180gataacgcat taacagcatt aaaccaagcg aaacatgatt taactgcaga tacacatgcc 3240ttagagcaag cagtgcaaca attgaatcgc acaggtacaa cgactggtaa gaagccggca 3300agtattactg cttacaataa ttcgattcgt gcacttcaaa gtgacttaac aagtgctaaa 3360aatagcgcta atgctattat tcaaaagcca ataagaacag tacaagaagt gcaatctgcg 3420ttaacaaatg taaatcgtgt caatgagcga ttaacgcaag caattaatca attagtacct 3480ttagctgata atagtgcttt aaaaactgct aagacgaaac ttgatgaaga aatcaataaa 3540tcagtaacta ctgatggtat gacacaatca tcaatccaag catatgaaaa tgctaaacgt 3600gcgggtcaaa cagaatcaac aaatgcacaa aatgttatta acaatggtga tgcgactgac 3660caacaaattg ccgcagaaaa aacaaaagta gaagaaaaat ataatagctt aaaacaagca 3720attgctggat taactccaga cttggcacca ttacaaactg caaaaactca gttgcaaaat 3780gatattgatc agccaacgag tacgactggt atgacaagcg catctattgc agcatttaat 3840gaaaaacttt cagcagctag aactaaaatt caagaaattg atcgtgtatt agcctcacat 3900ccagatgttg cgacaatacg tcaaaacgtg acagcagcga atgccgctaa atcagcactt 3960gatcaagcac gtaatggctt aacagtcgat aaagcgcctt tagaaaatgc gaaaaatcaa 4020ctacaatata gtattgacac gcaaacaagt acaactggta tgacacaaga ctctataaat 4080gcatacaatg cgaagttaac agctgcacgt aataagattc aacaaatcaa tcaagtatta 4140gcaggttcac cgactgtaga acaaattaat acaaatacgt ctacagcaaa tcaagctaaa 4200tctgatttag atcatgcacg tcaagcttta acaccagata aagcgccgct tcaaactgcg 4260aaaacgcaat tagaacaaag cattaatcaa ccaacggata caacaggtat gacgaccgct 4320tcgttaaatg cgtacaacca aaaattacaa gcagcgcgtc aaaagttaac tgaaattaat 4380caagtgttga atggcaaccc aactgtccaa aatatcaatg ataaagtgac agaggcaaac 4440caagctaagg atcaattaaa tacagcacgt caaggtttaa cattagatag acagccagcg 4500ttaacaacat tacatggtgc atctaactta aaccaagcac aacaaaataa tttcacgcaa 4560caaattaatg ctgctcaaaa tcatgctgcg cttgaaacaa ttaagtctaa cattacggct 4620ttaaatactg cgatgacgaa attaaaagac agtgttgcgg ataataatac aattaaatca 4680gatcaaaatt acactgacgc aacaccagct aataaacaag cgtatgataa tgcagttaat 4740gcggctaaag gtgtcattgg agaaacgact aatccaacga tggatgttaa cacagtgaac 4800caaaaagcag catctgttaa atcgacgaaa gatgctttag atggtcaaca aaacttacaa 4860cgtgcgaaaa cagaagcaac aaatgcgatt acgcatgcaa gtgatttaaa ccaagcacaa 4920aagaatgcat taacacaaca agtgaatagt gcacaaaacg tgcaagcagt aaatgatatt 4980aaacaaacga ctcaaagctt aaatactgct atgacaggtt taaaacgtgg cgttgctaat 5040cataaccaag tcgtacaaag tgataattat gtcaacgcag atactaataa gaaaaatgat 5100tacaacaatg catacaacca tgcgaatgac attattaatg gtaatgcaca acatccagtt 5160ataacaccaa gtgatgttaa caatgcttta tcaaatgtca caagtaaaga acatgcattg 5220aatggtgaag ctaagttaaa tgctgcgaaa caagaagcga atactgcatt aggtcattta 5280aacaatttaa ataatgcaca acgtcaaaac ttacaatcgc aaattaatgg tgcgcatcaa 5340attgatgcag ttaatacaat taagcaaaat gcaacaaact tgaatagtgc aatgggtaac 5400ttaagacaag ctgttgcaga taaagatcaa gtgaaacgta cagaagatta tgcggatgca 5460gatacagcta aacaaaatgc atataacagt gcagtttcaa gtgccgaaac aatcattaat 5520caaacaacaa atccaacgat gtctgttgat gatgttaatc gtgcaacttc agctgttact 5580tctaataaaa atgcattaaa tggttatgaa aaattagcac aatctaaaac agatgctgca 5640agagcaattg atgcattacc acatttaaat aatgcacaaa aagcagatgt taaatctaaa 5700attaatgctg catcaaatat tgctggcgta aatactgtta aacaacaagg tacagattta 5760aatacagcga tgggtaactt gcaaggtgca atcaatgatg aacaaacgac gcttaatagt 5820caaaactatc aagatgcgac acctagtaag aaaacagcat acacaaatgc ggtacaagct 5880gcgaaagata ttttaaataa atcaaatggt caaaataaaa cgaaagatca agttactgaa 5940gcgatgaatc aagtgaattc tgctaaaaat aacttagatg gtacgcgttt attagatcaa 6000gcgaagcaaa cagcaaaaca gcagttaaat aatatgacgc atttaacaac tgcacaaaaa 6060acgaatttaa caaaccaaat taatagtggt actactgtcg ctggtgttca aacggttcaa 6120tcaaatgcca atacattaga tcaagccatg aatacgttaa gacaaagtat tgccaacaaa 6180gatgcgacta aagcaagtga agattacgta gatgctaata atgataagca aacagcatat 6240aacaacgcag tagctgctgc tgaaacgatt attaatgcta atagtaatcc agaaatgaat 6300ccaagtacga ttacacaaaa agcagagcaa gtgaatagtt ctaaaacggc acttaacggt 6360gatgaaaact tagctgctgc aaaacaaaat gcgaaaacgt acttaaacac attgacaagt 6420attacagatg ctcaaaagaa caatttgatt agtcaaatta ctagtgcgac aagagtgagt 6480ggtgttgata ctgtaaaaca aaatgcgcaa catctagacc aagctatggc tagcttacag 6540aatggtatta acaacgaatc tcaagtgaaa tcatctgaga aatatcgtga tgctgataca 6600aataaacaac aagagtatga taatgctatt actgcagcga aagcgatttt aaataaatcg 6660acaggtccaa acactgcgca aaatgcagtt gaagcagcat tacaacgtgt taataatgcg 6720aaagatgcat tgaatggtga tgcaaaatta attgcagctc aaaacgcagc gaaacaacat 6780ttaggtactt taacgcatat cactacagct caacgtaatg atttaacaaa tcaaatttca 6840caagctacaa acttagctgg tgttgaatct gttaaacaaa atgcgaatag tttagatggt 6900gctatgggta acttacaaac ggctatcaac gataagtcag gaacattagc gagccaaaac 6960ttcttggatg ctgatgagca aaaacgtaat gcatacaatc aagctgtatc agcagccgaa 7020accattttaa ataaacaaac tggaccgaat acagcgaaaa cagcagtcga acaagcactt 7080aataatgtta ataatgcgaa acatgcatta aatggtacgc aaaacttaaa caatgcgaaa 7140caagcagcga ttacagcaat caatggcgca tctgatttaa atcaaaaaca aaaagatgca 7200ttaaaagcac aagctaatgg tgctcaacgc gtatctaatg cacaagatgt acagcacaat 7260gcgactgaac tgaacacggc aatgggcaca ttaaaacatg ccatcgcaga taagacgaat 7320acgttagcaa gcagtaaata tgttaatgcc gatagcacta aacaaaatgc ttacacaact 7380aaagttacca atgctgaaca tattattagc ggtacgccaa cggttgttac gacaccttca 7440gaagtaacag ctgcagctaa tcaagtaaac agcgcgaaac aagaattaaa tggtgacgaa 7500agattacgtg aagcaaaaca aaacgccaat actgctattg atgcattaac acaattaaat 7560acacctcaaa aagctaaatt aaaagaacaa gtgggacaag ccaatagatt agaagacgta 7620caaactgttc aaacaaatgg acaagcattg aacaatgcaa tgaaaggctt aagagatagt 7680attgctaacg aaacaacagt caaaacaagt caaaactata cagacgcaag tccgaataac 7740caatcaacat ataatagcgc tgtgtcaaat gcgaaaggta tcattaatca aactaacaat 7800ccgactatgg atactagtgc gattacccaa gctacaacac aagtgaataa tgctaaaaat 7860ggtttaaacg gtgctgaaaa cttaagaaat gcacaaaaca ctgctaagca aaacttaaat 7920acattatcac acttaacaaa taaccaaaaa tctgccatct catcacaaat tgatc 7975<210>13<211>2001<212>DNA<213>Staphylococcus aureus<400>13gatcatggca ttgtatttaa tgcaagtcta cctttgtaca aagatgccat ccatcaaaaa 60ggatcaatgc gcagtaatga caatggtgat gatatgagta tgatggtggg tacagtgctg 120agtggctttg aatatcgagc gcaaaaagaa aagtatgata acttatataa attcttcaaa 180gaaaatgaaa agaaatatca atatacaggc tttacaaaag aggcaattaa caagacacaa 240aatgtcggat ataaaaatga atatttttat attacatact cttctagaag tttaaaagaa 300tatcgaaagt attatgaacc actgattcga aaaaatgata aagaatttaa agaaggaatg 360gaacgagcaa gaaaagaagt gaattacgct gcaaatacag atgctgttgc tacacttttt 420tctactaaga aaaactttac taaagacaat acagtagatg atgtaatcga actaagtgat 480aaattatata atttaaaaaa taaaccagat aaatctacaa tcacaataca aatagggaaa 540cccactatta atactaagaa agccttttat gatgataatc gtccaataga atatggggtg 600cacagtaaag atgaataaaa ttaatgatag ggatttaaca gaattaagta gttactgggt 660ttatcaaaat attgatataa aaaaagaatt taaagttaat ggaaaaaggt ttaaacaagt 720agacagttat aatgatgata agaatagtaa tttgaatggt gctgctgata ttaaaatata 780tgagttatta gatgataaaa gtaaaccaac tggtcaacag acaataattt atcaaggaac 840atctaatgag gcaattaatc caaataatcc attaaaatca tcggggtttg gagatgattg 900gctccaaaat gctaaattaa tgaataatga taatgaaagc acagattatt taaagcaaac 960agatcaatta tcaaatcaat ataaaataaa gttagaagat gcagatagat tatcaaatag 1020tgatttttta aaaaaatata gaatggaatc aagtaacttc aaaaacaaaa ccattgtggc 1080ggatggcggt aattcggaag gcggtgcagg agcaaaatat caaggagcga aacatccgaa 1140tgaaaaagtt gttgctactg actcagcaat gattccttat gctgcttggc agaaatttgc 1200tagaccacgc tttgataata tgattagttt taatagtacc aacgatttat taacatggtt 1260acaagatcca ttcatcaaag atatgccagg aaaacgcgtt aacattaatg atggtgtgcc 1320caggttagat actttaatag acagccatgt aggttataaa aggaagttaa atagaaaaga 1380taacacatac gatactgtac cactaatcaa aataaagtcg gtaaaagata cagaaattaa 1440aaatggaaaa aaagtaaaaa agactattaa cataacatta gatatggatg ggcgaattcc 1500aataaatgtt tggacaggag attcgattgc acgttctgga agaggaactt taattaaact 1560taatttagaa aatcttgatg cgttgagtaa actgattact ggtgaaacaa gtggtatgtt 1620agcagaatgc gtaatctttt taaatgaaag ttttaacatc tcagaaaatg aaaataaaaa 1680ttttgcagat agaaagaaac aattatcaga aggatttaag gataagatta acttatttca 1740gttagaagaa atggaaagaa ctttaattag taaaataaac tcacttgaag aagttgcaga 1800tgaaacaata gaaagtatta gtgctgttaa acacttatta cctgattttg cattggatgc 1860attaaaagaa agaattaatg agttgtttaa aggtataaaa tcttttatag aaaaagtgta 1920tgatagtata gataatgaaa ttttagaaat tttcaaaaat atagatcacg acttcagaga 1980tggagtatct gaagaaatga t 2001<210>14<211>106<212>PRT<213>Staphylococcus aureus<400>14Asp Gln Thr Lys Thr Gln Thr Ala His Thr Val Lys Thr Ala Gln Thr1 5 10 15Ala Gln Glu Gln Asn Lys Val Gln Thr Pro Val Lys Asp Val Ala Thr
20 25 30Ala Lys Ser Glu Ser Asn Asn Gln Ala Val Ser Asp Asn Lys Ser Gln
35 40 45Gln Thr Asn Lys Val Thr Lys His Asn Glu Thr Pro Lys Gln Ala Ser
50 55 60Lys Ala Lys Glu Leu Pro Lys Thr Gly Leu Thr Ser Val Asp Asn Phe65 70 75 80Ile Ser Thr Val Ala Phe Ala Thr Leu Ala Leu Leu Gly Ser Leu Ser
85 90 95Leu Leu Leu Phe Lys Arg Lys Glu Ser Lys
100 105<210>15<211>960<212>PRT<213>Staphylococcus aureus<400>15Asp Arg Ile Ile Glu Thr Ala Pro Thr Asp Tyr Leu Ser Trp Gly Val1 5 10 15Gly Ala Val Gly Asn Pro Arg Phe Ile Asn Val Glu Ile Val His Thr
20 25 30His Asp Tyr Ala Ser Phe Ala Arg Ser Met Asn Asn Tyr Ala Asp Tyr
35 40 45Ala Ala Thr Gln Leu Gln Tyr Tyr Gly Leu Lys Pro Asp Ser Ala Glu
50 55 60Tyr Asp Gly Asn Gly Thr Val Trp Thr His Tyr Ala Val Ser Lys Tyr65 70 75 80Leu Gly Gly Thr Asp His Ala Asp Pro His Gly Tyr Leu Arg Ser His
85 90 95Asn Tyr Ser Tyr Asp Gln Leu Tyr Asp Leu Ile Asn Glu Lys Tyr Leu
100 105 110Ile Lys Met Gly Lys Val Ala Pro Trp Gly Thr Gln Ser Thr Thr Thr
115 120 125Pro Thr Thr Pro Ser Lys Pro Thr Thr Pro Ser Lys Pro Ser Thr Gly
130 135 140Lys Leu Thr Val Ala Ala Asn Asn Gly Val Ala Gln Ile Lys Pro Thr145 150 155 160Asn Ser Gly Leu Tyr Thr Thr Val Tyr Asp Lys Thr Gly Lys Ala Thr
165 170 175Asn Glu Val Gln Lys Thr Phe Ala Val Ser Lys Thr Ala Thr Leu Gly
180 185 190Asn Gln Lys Phe Tyr Leu Val Gln Asp Tyr Asn Ser Gly Asn Lys Phe
195 200 205Gly Trp Val Lys Glu Gly Asp Val Val Tyr Asn Thr Ala Lys Ser Pro
210 215 220Val Asn Val Asn Gln Ser Tyr Ser Ile Lys Pro Gly Thr Lys Leu Tyr225 230 235 240Thr Val Pro Trp Gly Thr Ser Lys Gln Val Ala Gly Ser Val Ser Gly
245 250 255Ser Gly Asn Gln Thr Phe Lys Ala Ser Lys Gln Gln Gln Ile Asp Lys
260 265 270Ser Ile Tyr Leu Tyr Gly Ser Val Asn Gly Lys Ser Gly Trp Val Ser
275 280 285Lys Ala Tyr Leu Val Asp Thr Ala Lys Pro Thr Pro Thr Pro Thr Pro
290 295 300Lys Pro Ser Thr Pro Thr Thr Asn Asn Lys Leu Thr Val Ser Ser Leu305 310 315 320Asn Gly Val Ala Gln Ile Asn Ala Lys Asn Asn Gly Leu Phe Thr Thr
325 330 335Val Tyr Asp Lys Thr Gly Lys Pro Thr Lys Glu Val Gln Lys Thr Phe
340 345 350Ala Val Thr Lys Glu Ala Ser Leu Gly Gly Asn Lys Phe Tyr Leu Val
355 360 365Lys Asp Tyr Asn Ser Pro Thr Leu Ile Gly Trp Val Lys Gln Gly Asp
370 375 380Val Ile Tyr Asn Asn Ala Lys Ser Pro Val Asn Val Met Gln Thr Tyr385 390 395 400Thr Val Lys Pro Gly Thr Lys Leu Tyr Ser Val Pro Trp Gly Thr Tyr
405 410 415Lys Gln Glu Ala Gly Ala Val Ser Gly Thr Gly Asn Gln Thr Phe Lys
420 425 430Ala Thr Lys Gln Gln Gln Ile Asp Lys Ser Ile Tyr Leu Phe Gly Thr
435 440 445Val Asn Gly Lys Ser Gly Trp Val Ser Lys Ala Tyr Leu Ala Val Pro
450 455 460Ala Ala Pro Lys Lys Ala Val Ala Gln Pro Lys Thr Ala Val Lys Ala465 470 475 480Tyr Thr Val Thr Lys Pro Gln Thr Thr Gln Thr Val Ser Lys Ile Ala
485 490 495Gln Val Lys Pro Asn Asn Thr Gly Ile Arg Ala Ser Val Tyr Glu Lys
500 505 510Thr Ala Lys Asn Gly Ala Lys Tyr Ala Asp Arg Thr Phe Tyr Val Thr
515 520 525Lys Glu Arg Ala His Gly Asn Glu Thr Tyr Val Leu Leu Asn Asn Thr
530 535 540Ser His Asn Ile Pro Leu Gly Trp Phe Asn Val Lys Asp Leu Asn Val545 550 555 560Gln Asn Leu Gly Lys Glu Val Lys Thr Thr Gln Lys Tyr Thr Val Asn
565 570 575Lys Ser Asn Asn Gly Leu Ser Met Val Pro Trp Gly Thr Lys Asn Gln
580 585 590Val Ile Leu Thr Gly Asn Asn Ile Ala Gln Gly Thr Phe Asn Ala Thr
595 600 605Lys Gln Val Ser Val Gly Lys Asp Val Tyr Leu Tyr Gly Thr Ile Asn
610 615 620Asn Arg Thr Gly Trp Val Asn Ala Lys Asp Leu Thr Ala Pro Thr Ala625 630 635 640Val Lys Pro Thr Thr Ser Ala Ala Lys Asp Tyr Asn Tyr Thr Tyr Val
645 650 655Ile Lys Asn Gly Asn Gly Tyr Tyr Tyr Val Thr Pro Asn Ser Asp Thr
660 665 670Ala Lys Tyr Ser Leu Lys Ala Phe Asn Glu Gln Pro Phe Ala Val Val
675 680 685Lys Glu Gln Val Ile Asn Gly Gln Thr Trp Tyr Tyr Gly Lys Leu Ser
690 695 700Asn Gly Lys Leu Ala Trp Ile Lys Ser Thr Asp Leu Ala Lys Glu Leu705 710 715 720Ile Lys Tyr Asn Gln Thr Gly Met Ala Leu Asn Gln Val Ala Gln Ile
725 730 735Gln Ala Gly Leu Gln Tyr Lys Pro Gln Val Gln Arg Val Pro Gly Lys
740 745 750Trp Thr Gly Ala Asn Phe Asn Asp Val Lys His Ala Met Asp Thr Lys
755 760 765Arg Leu Ala Gln Asp Pro Ala Leu Lys Tyr Gln Phe Leu Arg Leu Asp
770 775 780Gln Pro Gln Asn Ile Ser Ile Asp Lys Ile Asn Gln Phe Leu Lys Gly785 790 795 800Lys Gly Val Leu Glu Asn Gln Gly Ala Ala Phe Asn Lys Ala Ala Gln
805 810 815Met Tyr Gly Ile Asn Glu Val Tyr Leu Ile Ser His Ala Leu Leu Glu
820 825 830Thr Gly Asn Gly Thr Ser Gln Leu Ala Lys Gly Ala Asp Val Val Asn
835 840 845Asn Lys Val Val Thr Asn Ser Asn Thr Lys Tyr His Asn Val Phe Gly
850 855 860Ile Ala Ala Tyr Asp Asn Asp Pro Leu Arg Glu Gly Ile Lys Tyr Ala865 870 875 880Lys Gln Ala Gly Trp Asp Thr Val Ser Lys Ala Ile Val Gly Gly Ala
885 890 895Lys Phe Ile Gly Asn Ser Tyr Val Lys Ala Gly Gln Asn Thr Leu Tyr
900 905 910Lys Met Arg Trp Asn Pro Ala His Pro Gly Thr His Gln Tyr Ala Thr
915 920 925Asp Val Asp Trp Ala Asn Ile Asn Ala Lys Ile Ile Lys Gly Tyr Tyr
930 935 940Asp Lys Ile Gly Glu Val Gly Lys Tyr Phe Asp Ile Pro Gln Tyr Lys945 950 955 960<210>16<211>386<212>PRT<213>Staphylococcus aureus<400>16Asp Gln Tyr Ser Glu Asp Ala Lys Lys Thr Gln Lys Asp Tyr Ala Ser1 5 10 15Gln Ser Lys Lys Asp Lys Asn Glu Lys Ser Asn Thr Lys Asn Pro Gln
20 25 30Leu Pro Thr Gln Asp Glu Leu Lys His Lys Ser Lys Pro Ala Gln Ser
35 40 45Phe Asn Asn Asp Val Asn Gln Lys Asp Thr Arg Ala Thr Ser Leu Phe
50 55 60Glu Thr Asp Pro Ser Ile Ser Asn Asn Asp Asp Ser Gly Gln Phe Asn65 70 75 80Val Val Asp Ser Lys Asp Thr Arg Gln Phe Val Lys Ser Ile Ala Lys
85 90 95Asp Ala His Arg Ile Gly Gln Asp Asn Asp Ile Tyr Ala Ser Val Met
100 105 110Ile Ala Gln Ala Ile Leu Glu Ser Asp Ser Gly Arg Ser Ala Leu Ala
115 120 125Lys Ser Pro Asn His Asn Leu Phe Gly Ile Lys Gly Ala Phe Glu Gly
130 135 140Asn Ser Val Pro Phe Asn Thr Leu Glu Ala Asp Gly Asn Gln Leu Tyr145 150 155 160Ser Ile Asn Ala Gly Phe Arg Lys Tyr Pro Ser Thr Lys Glu Ser Leu
165 170 175Lys Asp Tyr Ser Asp Leu Ile Lys Asn Gly Ile Asp Gly Asn Arg Thr
180 185 190Ile Tyr Lys Pro Thr Trp Lys Ser Glu Ala Asp Ser Tyr Lys Asp Ala
195 200 205Thr Ser His Leu Ser Lys Thr Tyr Ala Thr Asp Pro Asn Tyr Ala Lys
210 215 220Lys Leu Asn Ser Ile Ile Lys His Tyr Gln Leu Thr Gln Phe Asp Asp225 230 235 240Glu Arg Met Pro Asp Leu Asp Lys Tyr Glu Arg Ser Ile Lys Asp Tyr
245 250 255Asp Asp Ser Ser Asp Glu Phe Lys Pro Phe Arg Glu Val Ser Asp Ser
260 265 270Met Pro Tyr Pro His Gly Gln Cys Thr Trp Tyr Val Tyr Asn Arg Met
275 280 285Lys Gln Phe Gly Thr Ser Ile Ser Gly Asp Leu Gly Asp Ala His Asn
290 295 300Trp Asn Asn Arg Ala Gln Tyr Arg Asp Tyr Gln Val Ser His Thr Pro305 310 315 320Lys Arg His Ala Ala Val Val Phe Glu Ala Gly Gln Phe Gly Ala Asp
325 330 335Gln His Tyr Gly His Val Ala Phe Val Glu Lys Val Asn Ser Asp Gly
340 345 350Ser Ile Val Ile Ser Glu Ser Asn Val Lys Gly Leu Gly Ile Ile Ser
355 360 365His Arg Thr Ile Asn Ala Ala Ala Ala Glu Glu Leu Ser Tyr Ile Thr
370 375 380Gly Lys385<210>17<211>325<212>PRT<213>Staphylococcus aureus<400>17Met Lys Met Asn Lys Leu Val Lys Ser Ser Val Ala Thr Ser Met Ala1 5 10 15Leu Leu Leu Leu Ser Gly Thr Ala Asn Ala Glu Gly Lys Ile Thr Pro
20 25 30Val Ser Val Lys Lys Val Asp Asp Lys Val Thr Leu Tyr Lys Thr Thr
35 40 45Ala Thr Ala Asp Ser Asp Lys Phe Lys Ile Ser Gln Ile Leu Thr Phe
50 55 60Asn Phe Ile Lys Asp Lys Ser Tyr Asp Lys Asp Thr Leu Val Leu Lys65 70 75 80Ala Thr Gly Asn Ile Asn Ser Gly Phe Val Lys Pro Asn Pro Asn Asp
85 90 95Tyr Asp Phe Ser Lys Leu Tyr Trp Gly Ala Lys Tyr Asn Val Ser Ile
100 105 110Ser Ser Gln Ser Asn Asp Ser Val Asn Val Val Asp Tyr Ala Pro Lys
115 120 125Asn Gln Asn Glu Glu Phe Gln Val Gln Asn Thr Leu Gly Tyr Thr Phe
130 135 140Gly Gly Asp Ile Ser Ile Ser Asn Gly Leu Ser Gly Gly Leu Asn Gly145 150 155 160Asn Thr Ala Phe Ser Glu Thr Ile Asn Tyr Lys Gln Glu Ser Tyr Arg
165 170 175Thr Thr Leu Ser Arg Asn Thr Asn Tyr Lys Asn Val Gly Trp Gly Val
180 185 190Glu Ala His Lys Ile Met Asn Asn Gly Trp Gly Pro Tyr Gly Arg Asp
195 200 205Ser Phe His Pro Thr Tyr Gly Asn Glu Leu Phe Leu Ala Gly Arg Gln
210 215 220Ser Ser Ala Tyr Ala Gly Gln Asn Phe Ile Ala Gln His Gln Met Pro225 230 235 240Leu Leu Ser Arg Ser Asn Phe Asn Pro Glu Phe Leu Ser Val Leu Ser
245 250 255His Arg Gln Asp Gly Ala Lys Lys Ser Lys Ile Thr Val Thr Tyr Gln
260 265 270Arg Glu Met Asp Leu Tyr Gln Ile Arg Trp Asn Gly Phe Tyr Trp Ala
275 280 285Gly Ala Asn Tyr Lys Asn Phe Lys Thr Arg Thr Phe Lys Ser Thr Tyr
290 295 300Glu Ile Asp Trp Glu Asn His Lys Val Lys Leu Leu Asp Thr Lys Glu305 310 315 320Thr Glu Asn Asn Lys
325<210>18<211>157<212>PRT<213>Staphylococcus aureus<400>18Ser Phe Asn Tyr Ser Lys Ser Ile Ser Tyr Thr Gln Gln Asn Tyr Val1 5 10 15Ser Glu Val Glu Gln Gln Asn Ser Lys Ser Val Leu Trp Gly Val Lys
20 25 30Ala Asn Ser Phe Ala Thr Glu Ser Gly Gln Lys Ser Ala Phe Asp Ser
35 40 45Asp Leu Phe Val Gly Tyr Lys Pro His Ser Lys Asp Pro Arg Asp Tyr
50 55 60Phe Val Pro Asp Ser Glu Leu Pro Pro Leu Val Gln Ser Gly Phe Asn65 70 75 80Pro Ser Phe Ile Ala Thr Val Ser His Glu Lys Gly Ser Ser Asp Thr
85 90 95Ser Glu Phe Glu Ile Thr Tyr Gly Arg Asn Met Asp Val Thr His Ala
100 105 110Ile Lys Arg Ser Thr His Tyr Gly Asn Ser Tyr Leu Asp Gly His Arg
115 120 125Val His Asn Ala Phe Val Asn Arg Asn Tyr Thr Val Lys Tyr Glu Val
130 135 140Asn Trp Lys Thr His Glu Ile Lys Val Lys Gly Gln Asn145 150 155<210>19<211>345<212>PRT<213>Staphylococcus aureus<400>19Ile Ile Ala Ile Ile Ile Leu Ile Phe Ile Ser Phe Phe Phe Ser Gly1 5 10 15Ser Glu Thr Ala Leu Thr Ala Ala Asn Lys Ala Lys Phe Lys Thr Glu
20 25 30Ala Asp Lys Gly Asp Lys Lys Ala Lys Gly Ile Val Lys Leu Leu Glu
35 40 45Lys Pro Ser Glu Phe Ile Thr Thr Ile Leu Ile Gly Asn Asn Val Ala
50 55 60Asn Ile Leu Leu Pro Thr Leu Val Thr Ile Met Ala Leu Arg Trp Gly65 70 75 80Ile Ser Val Gly Ile Ala Ser Ala Val Leu Thr Val Val Ile Ile Leu
85 90 95Ile Ser Glu Val Ile Pro Lys Ser Val Ala Ala Thr Phe Pro Asp Lys
100 105 110Ile Thr Arg Leu Val Tyr Pro Ile Ile Asn Ile Cys Val Ile Val Phe
115 120 125Arg Pro Ile Thr Leu Leu Leu Asn Lys Leu Thr Asp Ser Ile Asn Arg
130 135 140Ser Leu Ser Lys Gly Gln Pro Gln Glu His Gln Phe Ser Lys Glu Glu145 150 155 160Phe Lys Thr Met Leu Ala Ile Ala Gly His Glu Gly Ala Leu Asn Glu
165 170 175Ile Glu Thr Ser Arg Leu Glu Gly Val Ile Asn Phe Glu Asn Leu Lys
180 185 190Val Lys Asp Val Asp Thr Thr Pro Arg Ile Asn Val Thr Ala Phe Ala
195 200 205Ser Asn Ala Thr Tyr Glu Glu Val Tyr Glu Thr Val Met Asn Lys Pro
210 215 220Tyr Thr Arg Tyr Pro Val Tyr Glu Gly Asp Ile Asp Asn Ile Ile Gly225 230 235 240Val Phe His Ser Lys Tyr Leu Leu Ala Trp Ser Asn Lys Lys Glu Asn
245 250 255Gln Ile Thr Asn Tyr Ser Ala Lys Pro Leu Phe Val Asn Glu His Asn
260 265 270Lys Ala Glu Trp Val Leu Arg Lys Met Thr Ile Ser Arg Lys His Leu
275 280 285Ala Ile Val Leu Asp Glu Phe Gly Gly Thr Glu Ala Ile Val Ser His
290 295 300Glu Asp Leu Ile Glu Glu Leu Leu Gly Met Glu Ile Glu Asp Glu Met305 310 315 320Asp Lys Lys Glu Lys Glu Lys Leu Ser Gln Gln Gln Ile Gln Phe Gln
325 330 335Gln Arg Lys Asn Arg Asn Val Ser Ile
340 345<210>20<211>133<212>PRT<213>Staphylococcus aureus<400>20Met Asn Lys Gln Gln Lys Glu Phe Lys Ser Phe Tyr Ser Ile Arg Lys1 5 10 15Ser Ser Leu Gly Val Ala Ser Val Ala Ile Ser Thr Leu Leu Leu Leu
20 25 30Met Ser Asn Gly Glu Ala Gln Ala Ala Ala Glu Glu Thr Gly Gly Thr
35 40 45Asn Thr Glu Ala Gln Pro Lys Thr Glu Ala Val Ala Ser Pro Thr Thr
50 55 60Thr Ser Glu Lys Ala Pro Glu Thr Lys Pro Val Ala Asn Ala Val Ser65 70 75 80Val Ser Asn Lys Glu Val Glu Ala Pro Thr Ser Glu Thr Lys Glu Ala
85 90 95Lys Glu Val Lys Glu Val Lys Ala Pro Lys Glu Thr Lys Glu Val Lys
100 105 110Pro Ala Ala Lys Ala Thr Asn Asn Thr Tyr Pro Ile Leu Asn Gln Glu
115 120 125Leu Ile Arg Ser Asp
130<210>21<211>205<212>PRT<213>Staphylococcus aureus<400>21Asp His Gly Ile Val Phe Asn Ala Ser Leu Pro Leu Tyr Lys Asp Ala1 5 10 15Ile His Gln Lys Gly Ser Met Arg Ser Asn Asp Asn Gly Asp Asp Met
20 25 30Ser Met Met Val Gly Thr Val Leu Ser Gly Phe Glu Tyr Arg Ala Gln
35 40 45Lys Glu Lys Tyr Asp Asn Leu Tyr Lys Phe Phe Lys Glu Asn Glu Lys
50 55 60Lys Tyr Gln Tyr Thr Gly Phe Thr Lys Glu Ala Ile Asn Lys Thr Gln65 70 75 80Asn Val Gly Tyr Lys Asn Glu Tyr Phe Tyr Ile Thr Tyr Ser Ser Arg
85 90 95Ser Leu Lys Glu Tyr Arg Lys Tyr Tyr Glu Pro Leu Ile Arg Lys Asn
100 105 110Asp Lys Glu Phe Lys Glu Gly Met Glu Arg Ala Arg Lys Glu Val Asn
115 120 125Tyr Ala Ala Asn Thr Asp Ala Val Ala Thr Leu Phe Ser Thr Lys Lys
130 135 140Asn Phe Thr Lys Asp Asn Thr Val Asp Asp Val Ile Glu Leu Ser Asp145 150 155 160Lys Leu Tyr Asn Leu Lys Asn Lys Pro Asp Lys Ser Thr Ile Thr Ile
165 170 175Gln Ile Gly Lys Pro Thr Ile Asn Thr Lys Lys Ala Phe Tyr Asp Asp
180 185 190Asn Arg Pro Ile Glu Tyr Gly Val His Ser Lys Asp Glu
195 200 205<210>22<211>510<212>PRT<213>Staphylococcus aureus<400>22Asp His Tyr Val Ile Gln Tyr Phe Ser Gly Leu Ile Gly Gly Arg Gly1 5 10 15Arg Arg Ala Asn Leu Tyr Gly Leu Phe Asn Lys Ala Ile Glu Phe Glu
20 25 30Asn Ser Ser Phe Arg Gly Leu Tyr Gln Phe Ile Arg Phe Ile Asp Glu
35 40 45Leu Ile Glu Arg Gly Lys Asp Phe Gly Glu Glu Asn Val Val Gly Pro
50 55 60Asn Asp Asn Val Val Arg Met Met Thr Ile His Ser Ser Lys Gly Leu65 70 75 80Glu Phe Pro Phe Val Ile Tyr Ser Gly Leu Ser Lys Asp Phe Asn Lys
85 90 95Arg Asp Leu Lys Gln Pro Val Ile Leu Asn Gln Gln Phe Gly Leu Gly
100 105 110Met Asp Tyr Phe Asp Val Asp Lys Glu Met Ala Phe Pro Ser Leu Ala
115 120 125Ser Val Ala Tyr Arg Ala Val Ala Glu Lys Glu Leu Val Ser Glu Glu
130 135 140Met Arg Leu Val Tyr Val Ala Leu Thr Arg Ala Lys Glu Gln Leu Tyr145 150 155 160Leu Ile Gly Arg Val Lys Asn Asp Lys Ser Leu Leu Glu Leu Glu Gln
165 170 175Leu Ser Ile Ser Gly Glu His Ile Ala Val Asn Glu Arg Leu Thr Ser
180 185 190Pro Asn Pro Phe His Leu Ile Tyr Ser Ile Leu Ser Lys His Gln Ser
195 200 205Ala Ser Ile Pro Asp Asp Leu Lys Phe Glu Lys Asp Ile Ala Gln Ile
210 215 220Glu Asp Ser Ser Arg Pro Asn Val Asn Ile Ser Ile Val Tyr Phe Glu225 230 235 240Asp Val Ser Thr Glu Thr Ile Leu Asp Asn Asp Glu Tyr Arg Ser Val
245 250 255Asn Gln Leu Glu Thr Met Gln Asn Gly Asn Glu Asp Val Lys Ala Gln
260 265 270Ile Lys His Gln Leu Asp Tyr Arg Tyr Pro Tyr Val Asn Asp Thr Lys
275 280 285Lys Pro Ser Lys Gln Ser Val Ser Glu Leu Lys Arg Gln Tyr Glu Thr
290 295 300Glu Glu Ser Gly Thr Ser Tyr Glu Arg Val Arg Gln Tyr Arg Ile Gly305 310 315 320Phe Ser Thr Tyr Glu Arg Pro Lys Phe Leu Ser Glu Gln Gly Lys Arg
325 330 335Lys Ala Asn Glu Ile Gly Thr Leu Met His Thr Val Met Gln His Leu
340 345 350Pro Phe Lys Lys Glu Arg Ile Ser Glu Val Glu Leu His Gln Tyr Ile
355 360 365Asp Gly Leu Ile Asp Lys His Ile Ile Glu Ala Asp Ala Lys Lys Asp
370 375 380Ile Arg Met Asp Glu Ile Met Thr Phe Ile Asn Ser Glu Leu Tyr Ser385 390 395 400Ile Ile Ala Glu Ala Glu Gln Val Tyr Arg Glu Leu Pro Phe Val Val
405 410 415Asn Gln Ala Leu Val Asp Gln Leu Pro Gln Gly Asp Glu Asp Val Ser
420 425 430Ile Ile Gln Gly Met Ile Asp Leu Ile Phe Val Lys Asp Gly Val His
435 440 445Tyr Phe Val Asp Tyr Lys Thr Asp Ala Phe Asn Arg Arg Arg Gly Met
450 455 460Thr Asp Glu Glu Ile Gly Thr Gln Leu Lys Asn Lys Tyr Lys Ile Gln465 470 475 480Met Lys Tyr Tyr Gln Asn Thr Leu Gln Thr Ile Leu Asn Lys Glu Val
485 490 495Lys Gly Tyr Leu Tyr Phe Phe Lys Phe Gly Thr Leu Gln Leu
500 505 510<210>23<211>124<212>PRT<213>Staphylococcus aureus<400>23Met Lys Phe Leu Ser Phe Lys Tyr Asn Asp Lys Thr Ser Tyr Gly Val1 5 10 15Lys Val Lys Arg Glu Asp Ala Val Trp Asp Leu Thr Gln Val Phe Ala
20 25 30Asp Phe Ala Glu Gly Asp Phe His Pro Lys Thr Leu Leu Ala Gly Leu
35 40 45Gln Gln Asn His Thr Leu Asp Phe Gln Glu Gln Val Arg Lys Ala Val
50 55 60Val Ala Ala Glu Asp Ser Gly Lys Ala Glu Asp Tyr Lys Ile Ser Phe65 70 75 80Asn Asp Ile Glu Phe Leu Pro Pro Val Thr Pro Pro Asn Asn Val Ile
85 90 95Ala Phe Gly Arg Asn Tyr Lys Asp His Ala Asn Glu Leu Asn His Glu
100 105 110Val Glu Lys Leu Tyr Val Phe Thr Lys Ala Ala Ser
115 120<210>24<211>180<212>PRT<213>Staphylococcus aureus<400>24Ser Gly Thr Gly Phe Ile Val Gly Lys Asn Thr Ile Val Thr Asn Lys1 5 10 15His Val Val Ala Gly Met Glu Ile Gly Ala His Ile Ile Ala His Pro
20 25 30Asn Gly Glu Tyr Asn Asn Gly Gly Phe Tyr Lys Val Lys Lys Ile Val
35 40 45Arg Tyr Ser Gly Gln Glu Asp Ile Ala Ile Leu His Val Glu Asp Lys
50 55 60Ala Val His Pro Lys Asn Arg Asn Phe Lys Asp Tyr Thr Gly Ile Leu65 70 75 80Lys Ile Ala Ser Glu Ala Lys Glu Asn Glu Arg Ile Ser Ile Val Gly
85 90 95Tyr Pro Glu Pro Tyr Ile Asn Lys Phe Gln Met Tyr Glu Ser Thr Gly
100 105 110Lys Val Leu Ser Val Lys Gly Asn Met Ile Ile Thr Asp Ala Phe Val
115 120 125Glu Pro Gly Asn Ser Gly Ser Ala Val Phe Asn Ser Lys Tyr Glu Val
130 135 140Val Gly Val His Phe Gly Gly Asn Gly Pro Gly Asn Lys Ser Thr Lys145 150 155 160Gly Tyr Gly Val Tyr Phe Ser Pro Glu Ile Lys Lys Phe Ile Ala Asp
165 170 175Asn Thr Asp Lys
180<210>25<211>239<212>PRT<213>Staphylococcus aureus<400>25Met Asn Lys Asn Ile Ile Ile Lys Ser Ile Ala Ala Leu Thr Ile Leu1 5 10 15Thr Ser Ile Thr Gly Val Gly Thr Thr Met Val Glu Gly Ile Gln Gln
20 25 30Thr Ala Lys Ala Glu Asn Thr Val Lys Gln Ile Thr Asn Thr Asn Val
35 40 45Ala Pro Tyr Ser Gly Val Thr Trp Met Gly Ala Gly Thr Gly Phe Val
50 55 60Val Gly Asn His Thr Ile Ile Thr Asn Lys His Val Thr Tyr His Met65 70 75 80Lys Val Gly Asp Glu Ile Lys Ala His Pro Asn Gly Phe Tyr Asn Asn
85 90 95Gly Gly Gly Leu Tyr Lys Val Thr Lys Ile Val Asp Tyr Pro Gly Lys
100 105 110Glu Asp Ile Ala Val Val Gln Val Glu Glu Lys Ser Thr Gln Pro Lys
115 120 125Gly Arg Lys Phe Lys Asp Phe Thr Ser Lys Phe Asn Ile Ala Ser Glu
130 135 140Ala Lys Glu Asn Glu Pro Ile Ser Val Ile Gly Tyr Pro Asn Pro Asn145 150 155 160Gly Asn Lys Leu Gln Met Tyr Glu Ser Thr Gly Lys Val Leu Ser Val
165 170 175Asn Gly Asn Ile Val Ser Ser Asp Ala Ile Ile Gln Pro Gly Ser Ser
180 185 190Gly Ser Pro Ile Leu Asn Ser Lys His Glu Ala Ile Gly Val Ile Tyr
195 200 205Ala Gly Asn Lys Pro Ser Gly Glu Ser Thr Arg Gly Phe Ala Val Tyr
210 215 220Phe Ser Pro Glu Ile Lys Lys Phe Ile Ala Asp Asn Leu Asp Lys225 230 235<210>26<211>470<212>PRT<213>Staphylococcus aureus<400>26Met Gly Cys Thr Val Lys Met Asn Lys Ile Asn Asp Arg Asp Leu Thr1 5 10 15Glu Leu Ser Ser Tyr Trp Val Tyr Gln Asn Ile Asp Ile Lys Lys Glu
20 25 30Phe Lys Val Asn Gly Lys Arg Phe Lys Gln Val Asp Ser Tyr Asn Asp
35 40 45Asp Lys Asn Ser Asn Leu Asn Gly Ala Ala Asp Ile Lys Ile Tyr Glu
50 55 60Leu Leu Asp Asp Lys Ser Lys Pro Thr Gly Gln Gln Thr Ile Ile Tyr65 70 75 80Gln Gly Thr Ser Asn Glu Ala Ile Asn Pro Asn Asn Pro Leu Lys Ser
85 90 95Ser Gly Phe Gly Asp Asp Trp Leu Gln Asn Ala Lys Leu Met Asn Asn
100 105 110Asp Asn Glu Ser Thr Asp Tyr Leu Lys Gln Thr Asp Gln Leu Ser Asn
115 120 125Gln Tyr Lys Ile Lys Leu Glu Asp Ala Asp Arg Leu Ser Asn Ser Asp
130 135 140Phe Leu Lys Lys Tyr Arg Met Glu Ser Ser Asn Phe Lys Asn Lys Thr145 150 155 160Ile Val Ala Asp Gly Gly Asn Ser Glu Gly Gly Ala Gly Ala Lys Tyr
165 170 175Gln Gly Ala Lys His Pro Asn Glu Lys Val Val Ala Thr Asp Ser Ala
180 185 190Met Ile Pro Tyr Ala Ala Trp Gln Lys Phe Ala Arg Pro Arg Phe Asp
195 200 205Asn Met Ile Ser Phe Asn Ser Thr Asn Asp Leu Leu Thr Trp Leu Gln
210 215 220Asp Pro Phe Ile Lys Asp Met Pro Gly Lys Arg Val Asn Ile Asn Asp225 230 235 240Gly Val Pro Arg Leu Asp Thr Leu Ile Asp Ser His Val Gly Tyr Lys
245 250 255Arg Lys Leu Asn Arg Lys Asp Asn Thr Tyr Asp Thr Val Pro Leu Ile
260 265 270Lys Ile Lys Ser Val Lys Asp Thr Glu Ile Lys Asn Gly Lys Lys Val
275 280 285Lys Lys Thr Ile Asn Ile Thr Leu Asp Met Asp Gly Arg Ile Pro Ile
290 295 300Asn Val Trp Thr Gly Asp Ser Ile Ala Arg Ser Gly Arg Gly Thr Leu305 310 315 320Ile Lys Leu Asn Leu Glu Asn Leu Asp Ala Leu Ser Lys Leu Ile Thr
325 330 335Gly Glu Thr Ser Gly Met Leu Ala Glu Cys Val Ile Phe Leu Asn Glu
340 345 350Ser Phe Asn Ile Ser Glu Asn Glu Asn Lys Asn Phe Ala Asp Arg Lys
355 360 365Lys Gln Leu Ser Glu Gly Phe Lys Asp Lys Ile Asn Leu Phe Gln Leu
370 375 380Glu Glu Met Glu Arg Thr Leu Ile Ser Lys Ile Asn Ser Leu Glu Glu385 390 395 400Val Ala Asp Glu Thr Ile Glu Ser Ile Ser Ala Val Lys His Leu Leu
405 410 415Pro Asp Phe Ala Leu Asp Ala Leu Lys Glu Arg Ile Asn Glu Leu Phe
420 425 430Lys Gly Ile Lys Ser Phe Ile Glu Lys Val Tyr Asp Ser Ile Asp Asn
435 440 445Glu Ile Leu Glu Ile Phe Lys Asn Ile Asp His Asp Phe Arg Asp Gly
450 455 460Val Ser Glu Glu Met Met465 470<210>27<211>306<212>PRT<213>Staphylococcus aureus<400>27Met Lys Lys Lys Asp Gly Thr Gln Gln Phe Tyr His Tyr Ala Ser Ser1 5 10 15Val Lys Pro Ala Arg Val Ile Phe Thr Asp Ser Lys Pro Glu Ile Glu
20 25 30Leu Gly Leu Gln Ser Gly Gln Phe Trp Arg Lys Phe Glu Val Tyr Glu
35 40 45Gly Asp Lys Lys Leu Pro Ile Lys Leu Val Ser Tyr Asp Thr Val Lys
50 55 60Asp Tyr Ala Tyr Ile Arg Phe Ser Val Ser Asn Gly Thr Lys Ala Val65 70 75 80Lys Ile Val Ser Ser Thr His Phe Asn Asn Lys Glu Glu Lys Tyr Asp
85 90 95Tyr Thr Leu Met Glu Phe Ala Gln Pro Ile Tyr Asn Ser Ala Asp Lys
100 105 110Phe Lys Thr Glu Glu Asp Tyr Lys Ala Glu Lys Leu Leu Ala Pro Tyr
115 120 125Lys Lys Ala Lys Thr Leu Glu Arg Gln Val Tyr Glu Leu Asn Lys Ile
130 135 140Gln Asp Lys Leu Pro Glu Lys Leu Lys Ala Glu Tyr Lys Lys Lys Leu145 150 155 160Glu Asp Thr Lys Lys Ala Leu Asp Glu Gln Val Lys Ser Ala Ile Thr
165 170 175Glu Phe Gln Asn Val Gln Pro Thr Asn Glu Lys Met Thr Asp Leu Gln
180 185 190Asp Thr Lys Tyr Val Val Tyr Glu Ser Val Glu Asn Asn Glu Ser Met
195 200 205Met Asp Thr Phe Val Lys His Pro Ile Lys Thr Gly Met Leu Asn Gly
210 215 220Lys Lys Tyr Met Val Met Glu Thr Thr Asn Asp Asp Tyr Trp Lys Asp225 230 235 240Phe Met Val Glu Gly Gln Arg Val Arg Thr Ile Ser Lys Asp Ala Lys
245 250 255Asn Asn Thr Arg Thr Ile Ile Phe Pro Tyr Val Glu Gly Lys Thr Leu
260 265 270Tyr Asp Ala Ile Val Lys Val His Val Lys Thr Ile Asp Tyr Asp Gly
275 280 285Gln Tyr His Val Arg Ile Val Asp Lys Glu Ala Phe Thr Lys Ala His
290 295 300Thr Asp305<210>28<211>2659<212>PRT<213>Staphylococcus aureus<400>28Asp Gln Thr Thr Ile Ile Asn Ser Leu Thr Phe Thr Glu Thr Val Pro1 5 10 15Asn Arg Ser Tyr Ala Arg Ala Ser Ala Asn Glu Ile Thr Ser Lys Thr
20 25 30Val Ser Asn Val Ser Arg Thr Gly Asn Asn Ala Asn Val Thr Val Thr
35 40 45Val Thr Tyr Gln Asp Gly Thr Thr Ser Thr Val Thr Val Pro Val Lys
50 55 60His Val Ile Pro Glu Ile Val Ala His Ser His Tyr Thr Val Gln Gly65 70 75 80Gln Asp Phe Pro Ala Gly Asn Gly Ser Ser Ala Ser Asp Tyr Phe Lys
85 90 95Leu Ser Asn Gly Ser Asp Ile Ala Asp Ala Thr Ile Thr Trp Val Ser
100 105 110Gly Gln Ala Pro Asn Lys Asp Asn Thr Arg Ile Gly Glu Asp Ile Thr
115 120 125Val Thr Ala His Ile Leu Ile Asp Gly Glu Thr Thr Pro Ile Thr Lys
130 135 140Thr Ala Thr Tyr Lys Val Val Arg Thr Val Pro Lys His Val Phe Glu145 150 155 160Thr Ala Arg Gly Val Leu Tyr Pro Gly Val Ser Asp Met Tyr Asp Ala
165 170 175Lys Gln Tyr Val Lys Pro Val Asn Asn Ser Trp Ser Thr Asn Ala Gln
180 185 190His Met Asn Phe Gln Phe Val Gly Thr Tyr Gly Pro Asn Lys Asp Val
195 200 205Val Gly Ile Ser Thr Arg Leu Ile Arg Val Thr Tyr Asp Asn Arg Gln
210 215 220Thr Glu Asp Leu Thr Ile Leu Ser Lys Val Lys Pro Asp Pro Pro Arg225 230 235 240Ile Asp Ala Asn Ser Val Thr Tyr Lys Ala Gly Leu Thr Asn Gln Glu
245 250 255Ile Lys Val Asn Asn Val Leu Asn Asn Ser Ser Val Lys Leu Phe Lys
260 265 270Ala Asp Asn Thr Pro Leu Asn Val Thr Asn Ile Thr His Gly Ser Gly
275 280 285Phe Ser Ser Val Val Thr Val Ser Asp Ala Leu Pro Asn Gly Gly Ile
290 295 300Lys Ala Lys Ser Ser Ile Ser Met Asn Asn Val Thr Tyr Thr Thr Gln305 310 315 320Asp Glu His Gly Gln Val Val Thr Val Thr Arg Asn Glu Ser Val Asp
325 330 335Ser Asn Asp Ser Ala Thr Val Thr Val Thr Pro Gln Leu Gln Ala Thr
340 345 350Thr Glu Gly Ala Val Phe Ile Lys Gly Gly Asp Gly Phe Asp Phe Gly
355 360 365His Val Glu Arg Phe Ile Gln Asn Pro Pro His Gly Ala Thr Val Ala
370 375 380Trp His Asp Ser Pro Asp Thr Trp Lys Asn Thr Val Gly Asn Thr His385 390 395 400Lys Thr Ala Val Val Thr Leu Pro Asn Gly Gln Gly Thr Arg Asn Val
405 410 415Glu Val Pro Val Lys Val Tyr Pro Val Ala Asn Ala Lys Ala Pro Ser
420 425 430Arg Asp Val Lys Gly Gln Asn Leu Thr Asn Gly Thr Asp Ala Met Asn
435 440 445Tyr Ile Thr Phe Asp Pro Asn Thr Asn Thr Asn Gly Ile Thr Ala Ala
450 455 460Trp Ala Asn Arg Gln Gln Pro Asn Asn Gln Gln Ala Gly Val Gln His465 470 475 480Leu Asn Val Asp Val Thr Tyr Pro Gly Ile Ser Ala Ala Lys Arg Val
485 490 495Pro Val Thr Val Asn Val Tyr Gln Phe Glu Phe Pro Gln Thr Thr Tyr
500 505 510Thr Thr Thr Val Gly Gly Thr Leu Ala Ser Gly Thr Gln Ala Ser Gly
515 520 525Tyr Ala His Met Gln Asn Ala Thr Gly Leu Pro Thr Asp Gly Phe Thr
530 535 540Tyr Lys Trp Asn Arg Asp Thr Thr Gly Thr Asn Asp Ala Asn Trp Ser545 550 555 560Ala Met Asn Lys Pro Asn Val Ala Lys Val Val Asn Ala Lys Tyr Asp
565 570 575Val Ile Tyr Asn Gly His Thr Phe Ala Thr Ser Leu Pro Ala Lys Phe
580 585 590Val Val Lys Asp Val Gln Pro Ala Lys Pro Thr Val Thr Glu Thr Ala
595 600 605Ala Gly Ala Ile Thr Ile Ala Pro Gly Ala Asn Gln Thr Val Asn Thr
610 615 620His Ala Gly Asn Val Thr Thr Tyr Ala Asp Lys Leu Val Ile Lys Arg625 630 635 640Asn Gly Asn Val Val Thr Thr Phe Thr Arg Arg Asn Asn Thr Ser Pro
645 650 655Trp Val Lys Glu Ala Ser Ala Ala Thr Val Ala Gly Ile Ala Gly Thr
660 665 670Asn Asn Gly Ile Thr Val Ala Ala Gly Thr Phe Asn Pro Ala Asp Thr
675 680 685Ile Gln Val Val Ala Thr Gln Gly Ser Gly Glu Thr Val Ser Asp Glu
690 695 700Gln Arg Ser Asp Asp Phe Thr Val Val Ala Pro Gln Pro Asn Gln Ala705 710 715 720Thr Thr Lys Ile Trp Gln Asn Gly His Ile Asp Ile Thr Pro Asn Asn
725 730 735Pro Ser Gly His Leu Ile Asn Pro Thr Gln Ala Met Asp Ile Ala Tyr
740 745 750Thr Glu Lys Val Gly Asn Gly Ala Glu His Ser Lys Thr Ile Asn Val
755 760 765Val Arg Gly Gln Asn Asn Gln Trp Thr Ile Ala Asn Lys Pro Asp Tyr
770 775 780Val Thr Leu Asp Ala Gln Thr Gly Lys Val Thr Phe Asn Ala Asn Thr785 790 795 800Ile Lys Pro Asn Ser Ser Ile Thr Ile Thr Pro Lys Ala Gly Thr Gly
805 810 815His Ser Val Ser Ser Asn Pro Ser Thr Leu Thr Ala Pro Ala Ala His
820 825 830Thr Val Asn Thr Thr Glu Ile Val Lys Asp Tyr Gly Ser Asn Val Thr
835 840 845Ala Ala Glu Ile Asn Asn Ala Val Gln Val Ala Asn Lys Arg Thr Ala
850 855 860Thr Ile Lys Asn Gly Thr Ala Met Pro Thr Asn Leu Ala Gly Gly Ser865 870 875 880Thr Thr Thr Ile Pro Val Thr Val Thr Tyr Asn Asp Gly Ser Thr Glu
885 890 895Glu Val Gln Glu Ser Ile Phe Thr Lys Ala Asp Lys Arg Glu Leu Ile
900 905 910Thr Ala Lys Asn His Leu Asp Asp Pro Val Ser Thr Glu Gly Lys Lys
915 920 925Pro Gly Thr Ile Thr Gln Tyr Asn Asn Ala Met His Asn Ala Gln Gln
930 935 940Gln Ile Asn Thr Ala Lys Thr Glu Ala Gln Gln Val Ile Asn Asn Glu945 950 955 960Arg Ala Thr Pro Gln Gln Val Ser Asp Ala Leu Thr Lys Val Arg Ala
965 970 975Ala Gln Thr Lys Ile Asp Gln Ala Lys Ala Leu Leu Gln Asn Lys Glu
980 985 990Asp Asn Ser Gln Leu Val Thr Ser Lys Asn Asn Leu Gln Ser Ser Val
995 1000 1005Asn Gln Val Pro Ser Thr Ala Gly Met Thr Gln Gln Ser Ile Asp Asn1010 1015 1020Tyr Asn Ala Lys Lys Arg Glu Ala Glu Thr Glu Ile Thr Ala Ala Gln1025 1030 1035 1040Arg Val Ile Asp Asn Gly Asp Ala Thr Ala Gln Gln Ile Ser Asp Glu
1045 1050 1055Lys His Arg Val Asp Asn Ala Leu Thr Ala Leu Asn Gln Ala Lys His
1060 1065 1070Asp Leu Thr Ala Asp Thr His Ala Leu Glu Gln Ala Val Gln Gln Leu
1075 1080 1085Asn Arg Thr Gly Thr Thr Thr Gly Lys Lys Pro Ala Ser Ile Thr Ala1090 1095 1100Tyr Asn Asn Ser Ile Arg Ala Leu Gln Ser Asp Leu Thr Ser Ala Lys1105 1110 1115 1120Asn Ser Ala Asn Ala Ile Ile Gln Lys Pro Ile Arg Thr Val Gln Glu
1125 1130 1135Val Gln Ser Ala Leu Thr Asn Val Asn Arg Val Asn Glu Arg Leu Thr
1140 1145 1150Gln Ala Ile Asn Gln Leu Val Pro Leu Ala Asp Asn Ser Ala Leu Lys
1155 1160 1165Thr Ala Lys Thr Lys Leu Asp Glu Glu Ile Asn Lys Ser Val Thr Thr1170 1175 1180Asp Gly Met Thr Gln Ser Ser Ile Gln Ala Tyr Glu Asn Ala Lys Arg1185 1190 1195 1200Ala Gly Gln Thr Glu Ser Thr Asn Ala Gln Asn Val Ile Asn Asn Gly
1205 1210 1215Asp Ala Thr Asp Gln Gln Ile Ala Ala Glu Lys Thr Lys Val Glu Glu
1220 1225 1230Lys Tyr Asn Ser Leu Lys Gln Ala Ile Ala Gly Leu Thr Pro Asp Leu
1235 1240 1245Ala Pro Leu Gln Thr Ala Lys Thr Gln Leu Gln Asn Asp Ile Asp Gln1250 1255 1260Pro Thr Ser Thr Thr Gly Met Thr Ser Ala Ser Ile Ala Ala Phe Asn1265 1270 1275 1280Glu Lys Leu Ser Ala Ala Arg Thr Lys Ile Gln Glu Ile Asp Arg Val
1285 1290 1295Leu Ala Ser His Pro Asp Val Ala Thr Ile Arg Gln Asn Val Thr Ala
1300 1305 1310Ala Asn Ala Ala Lys Ser Ala Leu Asp Gln Ala Arg Asn Gly Leu Thr
1315 1320 1325Val Asp Lys Ala Pro Leu Glu Asn Ala Lys Asn Gln Leu Gln Tyr Ser1330 1335 1340Ile Asp Thr Gln Thr Ser Thr Thr Gly Met Thr Gln Asp Ser Ile Asn1345 1350 1355 1360Ala Tyr Asn Ala Lys Leu Thr Ala Ala Arg Asn Lys Ile Gln Gln Ile
1365 1370 1375Asn Gln Val Leu Ala Gly Ser Pro Thr Val Glu Gln Ile Asn Thr Asn
1380 1385 1390Thr Ser Thr Ala Asn Gln Ala Lys Ser Asp Leu Asp His Ala Arg Gln
1395 1400 1405Ala Leu Thr Pro Asp Lys Ala Pro Leu Gln Thr Ala Lys Thr Gln Leu1410 1415 1420Glu Gln Ser Ile Asn Gln Pro Thr Asp Thr Thr Gly Met Thr Thr Ala1425 1430 1435 1440Ser Leu Asn Ala Tyr Asn Gln Lys Leu Gln Ala Ala Arg Gln Lys Leu
1445 1450 1455Thr Glu Ile Asn Gln Val Leu Asn Gly Asn Pro Thr Val Gln Asn Ile
1460 1465 1470Asn Asp Lys Val Thr Glu Ala Asn Gln Ala Lys Asp Gln Leu Asn Thr
1475 1480 1485Ala Arg Gln Gly Leu Thr Leu Asp Arg Gln Pro Ala Leu Thr Thr Leu1490 1495 1500His Gly Ala Ser Asn Leu Asn Gln Ala Gln Gln Asn Asn Phe Thr Gln1505 1510 1515 1520Gln Ile Asn Ala Ala Gln Asn His Ala Ala Leu Glu Thr Ile Lys Ser
1525 1530 1535Asn Ile Thr Ala Leu Asn Thr Ala Met Thr Lys Leu Lys Asp Ser Val
1540 1545 1550Ala Asp Asn Asn Thr Ile Lys Ser Asp Gln Asn Tyr Thr Asp Ala Thr
1555 1560 1565Pro Ala Asn Lys Gln Ala Tyr Asp Asn Ala Val Asn Ala Ala Lys Gly1570 1575 1580Val Ile Gly Glu Thr Thr Asn Pro Thr Met Asp Val Asn Thr Val Asn1585 1590 1595 1600Gln Lys Ala Ala Ser Val Lys Ser Thr Lys Asp Ala Leu Asp Gly Gln
1605 1610 1615Gln Asn Leu Gln Arg Ala Lys Thr Glu Ala Thr Asn Ala Ile Thr His
1620 1625 1630Ala Ser Asp Leu Asn Gln Ala Gln Lys Asn Ala Leu Thr Gln Gln Val
1635 1640 1645Asn Ser Ala Gln Asn Val Gln Ala Val Asn Asp Ile Lys Gln Thr Thr1650 1655 1660Gln Ser Leu Asn Thr Ala Met Thr Gly Leu Lys Arg Gly Val Ala Asn1665 1670 1675 1680His Asn Gln Val Val Gln Ser Asp Asn Tyr Val Asn Ala Asp Thr Asn
1685 1690 1695Lys Lys Asn Asp Tyr Asn Asn Ala Tyr Asn His Ala Asn Asp Ile Ile
1700 1705 1710Asn Gly Asn Ala Gln His Pro Val Ile Thr Pro Ser Asp Val Asn Asn
1715 1720 1725Ala Leu Ser Asn Val Thr Ser Lys Glu His Ala Leu Asn Gly Glu Ala1730 1735 1740Lys Leu Asn Ala Ala Lys Gln Glu Ala Asn Thr Ala Leu Gly His Leu1745 1750 1755 1760Asn Asn Leu Asn Asn Ala Gln Arg Gln Asn Leu Gln Ser Gln Ile Asn
1765 1770 1775Gly Ala His Gln Ile Asp Ala Val Asn Thr Ile Lys Gln Asn Ala Thr
1780 1785 1790Asn Leu Asn Ser Ala Met Gly Asn Leu Arg Gln Ala Val Ala Asp Lys
1795 1800 1805Asp Gln Val Lys Arg Thr Glu Asp Tyr Ala Asp Ala Asp Thr Ala Lys1810 1815 1820Gln Asn Ala Tyr Asn Ser Ala Val Ser Ser Ala Glu Thr Ile Ile Asn1825 1830 1835 1840Gln Thr Thr Asn Pro Thr Met Ser Val Asp Asp Val Asn Arg Ala Thr
1845 1850 1855Ser Ala Val Thr Ser Asn Lys Asn Ala Leu Asn Gly Tyr Glu Lys Leu
1860 1865 1870Ala Gln Ser Lys Thr Asp Ala Ala Arg Ala Ile Asp Ala Leu Pro His
1875 1880 1885Leu Asn Asn Ala Gln Lys Ala Asp Val Lys Ser Lys Ile Asn Ala Ala1890 1895 1900Ser Asn Ile Ala Gly Val Asn Thr Val Lys Gln Gln Gly Thr Asp Leu1905 1910 1915 1920Asn Thr Ala Met Gly Asn Leu Gln Gly Ala Ile Asn Asp Glu Gln Thr
1925 1930 1935Thr Leu Asn Ser Gln Asn Tyr Gln Asp Ala Thr Pro Ser Lys Lys Thr
1940 1945 1950Ala Tyr Thr Asn Ala Val Gln Ala Ala Lys Asp Ile Leu Asn Lys Ser
1955 1960 1965Asn Gly Gln Asn Lys Thr Lys Asp Gln Val Thr Glu Ala Met Asn Gln1970 1975 1980Val Asn Ser Ala Lys Asn Asn Leu Asp Gly Thr Arg Leu Leu Asp Gln1985 1990 1995 2000Ala Lys Gln Thr Ala Lys Gln Gln Leu Asn Asn Met Thr His Leu Thr
2005 2010 2015Thr Ala Gln Lys Thr Asn Leu Thr Asn Gln Ile Asn Ser Gly Thr Thr
2020 2025 2030Val Ala Gly Val Gln Thr Val Gln Ser Asn Ala Asn Thr Leu Asp Gln
2035 2040 2045Ala Met Asn Thr Leu Arg Gln Ser Ile Ala Asn Lys Asp Ala Thr Lys2050 2055 2060Ala Ser Glu Asp Tyr Val Asp Ala Asn Asn Asp Lys Gln Thr Ala Tyr2065 2070 2075 2080Asn Asn Ala Val Ala Ala Ala Glu Thr Ile Ile Asn Ala Asn Ser Asn
2085 2090 2095Pro Glu Met Asn Pro Ser Thr Ile Thr Gln Lys Ala Glu Gln Val Asn
2100 2105 2110Ser Ser Lys Thr Ala Leu Asn Gly Asp Glu Asn Leu Ala Ala Ala Lys
2115 2120 2125Gln Asn Ala Lys Thr Tyr Leu Asn Thr Leu Thr Ser Ile Thr Asp Ala2130 2135 2140Gln Lys Asn Asn Leu Ile Ser Gln Ile Thr Ser Ala Thr Arg Val Ser2145 2150 2155 2160Gly Val Asp Thr Val Lys Gln Asn Ala Gln His Leu Asp Gln Ala Met
2165 2170 2175Ala Ser Leu Gln Asn Gly Ile Asn Asn Glu Ser Gln Val Lys Ser Ser
2180 2185 2190Glu Lys Tyr Arg Asp Ala Asp Thr Asn Lys Gln Gln Glu Tyr Asp Asn
2195 2200 2205Ala Ile Thr Ala Ala Lys Ala Ile Leu Asn Lys Ser Thr Gly Pro Asn2210 2215 2220Thr Ala Gln Asn Ala Val Glu Ala Ala Leu Gln Arg Val Asn Asn Ala2225 2230 2235 2240Lys Asp Ala Leu Asn Gly Asp Ala Lys Leu Ile Ala Ala Gln Asn Ala
2245 2250 2255Ala Lys Gln His Leu Gly Thr Leu Thr His Ile Thr Thr Ala Gln Arg
2260 2265 2270Asn Asp Leu Thr Asn Gln Ile Ser Gln Ala Thr Asn Leu Ala Gly Val
2275 2280 2285Glu Ser Val Lys Gln Asn Ala Asn Ser Leu Asp Gly Ala Met Gly Asn2290 2295 2300Leu Gln Thr Ala Ile Asn Asp Lys Ser Gly Thr Leu Ala Ser Gln Asn2305 2310 2315 2320Phe Leu Asp Ala Asp Glu Gln Lys Arg Asn Ala Tyr Asn Gln Ala Val
2325 2330 2335Ser Ala Ala Glu Thr Ile Leu Asn Lys Gln Thr Gly Pro Asn Thr Ala
2340 2345 2350Lys Thr Ala Val Glu Gln Ala Leu Asn Asn Val Asn Asn Ala Lys His
2355 2360 2365Ala Leu Asn Gly Thr Gln Asn Leu Asn Asn Ala Lys Gln Ala Ala Ile2370 2375 2380Thr Ala Ile Asn Gly Ala Ser Asp Leu Asn Gln Lys Gln Lys Asp Ala2385 2390 2395 2400Leu Lys Ala Gln Ala Asn Gly Ala Gln Arg Val Ser Asn Ala Gln Asp
2405 2410 2415Val Gln His Asn Ala Thr Glu Leu Asn Thr Ala Met Gly Thr Leu Lys
2420 2425 2430His Ala Ile Ala Asp Lys Thr Asn Thr Leu Ala Ser Ser Lys Tyr Val
2435 2440 2445Asn Ala Asp Ser Thr Lys Gln Asn Ala Tyr Thr Thr Lys Val Thr Asn2450 2455 2460Ala Glu His Ile Ile Ser Gly Thr Pro Thr Val Val Thr Thr Pro Ser2465 2470 2475 2480Glu Val Thr Ala Ala Ala Asn Gln Val Asn Ser Ala Lys Gln Glu Leu
2485 2490 2495Asn Gly Asp Glu Arg Leu Arg Glu Ala Lys Gln Asn Ala Asn Thr Ala
2500 2505 2510Ile Asp Ala Leu Thr Gln Leu Asn Thr Pro Gln Lys Ala Lys Leu Lys
2515 2520 2525Glu Gln Val Gly Gln Ala Asn Arg Leu Glu Asp Val Gln Thr Val Gln2530 2535 2540Thr Asn Gly Gln Ala Leu Asn Asn Ala Met Lys Gly Leu Arg Asp Ser2545 2550 2555 2560Ile Ala Asn Glu Thr Thr Val Lys Thr Ser Gln Asn Tyr Thr Asp Ala
2565 2570 2575Ser Pro Asn Asn Gln Ser Thr Tyr Asn Ser Ala Val Ser Asn Ala Lys
2580 2585 2590Gly Ile Ile Asn Gln Thr Asn Asn Pro Thr Met Asp Thr Ser Ala Ile
2595 2600 2605Thr Gln Ala Thr Thr Gln Val Asn Asn Ala Lys Asn Gly Leu Asn Gly2610 2615 2620Ala Glu Asn Leu Arg Asn Ala Gln Asn Thr Ala Lys Gln Asn Leu Asn2625 2630 2635 2640Thr Leu Ser His Leu Thr Asn Asn Gln Lys Ser Ala Ile Ser Ser Gln
2645 2650 2655Ile Asp Arg<210>29<211>496<212>PRT<213>Staphylococcus aureus<400>29Met Asn Met Lys Lys Lys Glu Lys His Ala Ile Arg Lys Lys Ser Ile1 5 10 15Gly Val Ala Ser Val Leu Val Gly Thr Leu Ile Gly Phe Gly Leu Leu
20 25 30Ser Ser Lys Glu Ala Asp Ala Ser Glu Asn Ser Val Thr Gln Ser Asp
35 40 45Ser Ala Ser Asn Glu Ser Lys Ser Asn Asp Ser Ser Ser Val Ser Ala
50 55 60Ala Pro Lys Thr Asp Asp Thr Asn Val Ser Asp Thr Lys Thr Ser Ser65 70 75 80Asn Thr Asn Asn Gly Glu Thr Ser Val Ala Gln Asn Pro Ala Gln Gln
85 90 95Glu Thr Thr Gln Ser Ser Ser Thr Asn Ala Thr Thr Glu Glu Thr Pro
100 105 110Val Thr Gly Glu Ala Thr Thr Thr Thr Thr Asn Gln Ala Asn Thr Pro
115 120 125Ala Thr Thr Gln Ser Ser Asn Thr Asn Ala Glu Glu Leu Val Asn Gln
130 135 140Thr Ser Asn Glu Thr Thr Phe Asn Asp Thr Asn Thr Val Ser Ser Val145 150 155 160Asn Ser Pro Gln Asn Ser Thr Asn Ala Glu Asn Val Ser Thr Thr Gln
165 170 175Asp Thr Ser Thr Glu Ala Thr Pro Ser Asn Asn Glu Ser Ala Pro Gln
180 185 190Ser Thr Asp Ala Ser Asn Lys Asp Val Val Asn Gln Ala Val Asn Thr
195 200 205Ser Ala Pro Arg Met Arg Ala Phe Ser Leu Ala Ala Val Ala Ala Asp
210 215 220Ala Pro Ala Ala Gly Thr Asp Ile Thr Asn Gln Leu Thr Asn Val Thr225 230 235 240Val Gly Ile Asp Ser Gly Thr Thr Val Tyr Pro His Gln Ala Gly Tyr
245 250 255Val Lys Leu Asn Tyr Gly Phe Ser Val Pro Asn Ser Ala Val Lys Gly
260 265 270Asp Thr Phe Lys Ile Thr Val Pro Lys Glu Leu Asn Leu Asn Gly Val
275 280 285Thr Ser Thr Ala Lys Val Pro Pro Ile Met Ala Gly Asp Gln Val Leu
290 295 300Ala Asn Gly Val Ile Asp Ser Asp Gly Asn Val Ile Tyr Thr Phe Thr305 310 315 320Asp Tyr Val Asn Thr Lys Asp Asp Val Lys Ala Thr Leu Thr Met Pro
325 330 335Ala Tyr Ile Asp Pro Glu Asn Val Lys Lys Thr Gly Asn Val Thr Leu
340 345 350Ala Thr Gly Ile Gly Ser Thr Thr Ala Asn Lys Thr Val Leu Val Asp
355 360 365Tyr Glu Lys Tyr Gly Lys Phe Tyr Asn Leu Ser Ile Lys Gly Thr Ile
370 375 380Asp Gln Ile Asp Lys Thr Asn Asn Thr Tyr Arg Gln Thr Ile Tyr Val385 390 395 400Asn Pro Ser Gly Asp Asn Val Ile Ala Pro Val Leu Thr Gly Asn Leu
405 410 415Lys Pro Asn Thr Asp Ser Asn Ala Leu Ile Asp Gln Gln Asn Thr Ser
420 425 430Ile Lys Val Tyr Lys Val Asp Asn Ala Ala Asp Leu Ser Glu Ser Tyr
435 440 445Phe Val Asn Pro Glu Asn Phe Glu Asp Val Thr Asn Ser Val Asn Ile
450 455 460Thr Phe Pro Asn Pro Asn Gln Tyr Lys Val Glu Phe Asn Thr Pro Asp465 470 475 480Asp Gln Ile Thr Thr Pro Tyr Ile Val Val Val Asn Gly His Ile Asp
485 490 495<210>30<211>541<212>PRT<213>Staphylococcus aureus<400>30Asp Gln Tyr Leu Leu Glu Arg Lys Lys Ser Gln Tyr Glu Asp Tyr Lys1 5 10 15Gln Trp Tyr Ala Asn Tyr Lys Lys Glu Asn Pro Arg Thr Asp Leu Lys
20 25 30Met Ala Asn Phe His Lys Tyr Asn Leu Glu Glu Leu Ser Met Lys Glu
35 40 45Tyr Asn Glu Leu Gln Asp Ala Leu Lys Arg Ala Leu Asp Asp Phe His
50 55 60Arg Glu Val Lys Asp Ile Lys Asp Lys Asn Ser Asp Leu Lys Thr Phe65 70 75 80Asn Ala Ala Glu Glu Asp Lys Ala Thr Lys Glu Val Tyr Asp Leu Val
85 90 95Ser Glu Ile Asp Thr Leu Val Val Ser Tyr Tyr Gly Asp Lys Asp Tyr
100 105 110Gly Glu His Ala Lys Glu Leu Arg Ala Lys Leu Asp Leu Ile Leu Gly
115 120 125Asp Thr Asp Asn Pro His Lys Ile Thr Asn Glu Arg Ile Lys Lys Glu
130 135 140Met Ile Asp Asp Leu Asn Ser Ile Ile Asp Asp Phe Phe Met Glu Thr145 150 155 160Lys Gln Asn Arg Pro Lys Ser Ile Thr Lys Tyr Asn Pro Thr Thr His
165 170 175Asn Tyr Lys Thr Asn Ser Asp Asn Lys Pro Asn Phe Asp Lys Leu Val
180 185 190Glu Glu Thr Lys Lys Ala Val Lys Glu Ala Asp Asp Ser Trp Lys Lys
195 200 205Lys Thr Val Lys Lys Tyr Gly Glu Thr Glu Thr Lys Ser Pro Val Val
210 215 220Lys Glu Glu Lys Lys Val Glu Glu Pro Gln Ala Pro Lys Val Asp Asn225 230 235 240Gln Gln Glu Val Lys Thr Thr Ala Gly Lys Ala Glu Glu Thr Thr Gln
245 250 255Pro Val Ala Gln Pro Leu Val Lys Ile Pro Gln Gly Thr Ile Thr Gly
260 265 270Glu Ile Val Lys Gly Pro Glu Tyr Pro Thr Met Glu Asn Lys Thr Val
275 280 285Gln Gly Glu Ile Val Gln Gly Pro Asp Phe Leu Thr Met Glu Gln Ser
290 295 300Gly Pro Ser Leu Ser Asn Asn Tyr Thr Asn Pro Pro Leu Thr Asn Pro305 310 315 320Ile Leu Glu Gly Leu Glu Gly Ser Ser Ser Lys Leu Glu Ile Lys Pro
325 330 335Gln Gly Thr Glu Ser Thr Leu Lys Gly Thr Gln Gly Glu Ser Ser Asp
340 345 350Ile Glu Val Lys Pro Gln Ala Thr Glu Thr Thr Glu Ala Ser Gln Tyr
355 360 365Gly Pro Arg Pro Gln Phe Asn Lys Thr Pro Lys Tyr Val Lys Tyr Arg
370 375 380Asp Ala Gly Thr Gly Ile Arg Glu Tyr Asn Asp Gly Thr Phe Gly Tyr385 390 395 400Glu Ala Arg Pro Arg Phe Asn Lys Pro Ser Glu Thr Asn Ala Tyr Asn
405 410 415Val Thr Thr His Ala Asn Gly Gln Val Ser Tyr Gly Ala Arg Pro Thr
420 425 430Tyr Lys Lys Pro Ser Glu Thr Asn Ala Tyr Asn Val Thr Thr His Ala
435 440 445Asn Gly Gln Val Ser Tyr Gly Ala Arg Pro Thr Gln Asn Lys Pro Ser
450 455 460Lys Thr Asn Ala Tyr Asn Val Thr Thr His Gly Asn Gly Gln Val Ser465 470 475 480Tyr Gly Ala Arg Gln Ala Gln Asn Lys Pro Ser Lys Thr Asn Ala Tyr
485 490 495Asn Val Thr Thr His Ala Asn Gly Gln Val Ser Tyr Gly Ala Arg Pro
500 505 510Thr Tyr Lys Lys Pro Ser Lys Thr Asn Ala Tyr Asn Val Thr Thr His
515 520 525Ala Asp Gly Thr Ala Thr Tyr Gly Pro Arg Val Thr Lys
530 535 540<210>31<211>356<212>PRT<213>Staphylococcus aureus<400>31Met Lys Met Arg Thr Ile Ala Lys Thr Ser Leu Ala Leu Gly Leu Leu1 5 10 15Thr Thr Gly Ala Ile Thr Val Thr Thr Gln Ser Val Lys Ala Glu Lys
20 25 30Ile Gln Ser Thr Lys Val Asp Lys Val Pro Thr Leu Lys Ala Glu Arg
35 40 45Leu Ala Met Ile Asn Ile Thr Ala Gly Ala Asn Ser Ala Thr Thr Gln
50 55 60Ala Ala Asn Thr Arg Gln Glu Arg Thr Pro Lys Leu Glu Lys Ala Pro65 70 75 80Asn Thr Asn Glu Glu Lys Thr Ser Ala Ser Lys Ile Glu Lys Ile Ser
85 90 95Gln Pro Lys Gln Glu Glu Gln Lys Thr Leu Asn Ile Ser Ala Thr Pro
100 105 110Ala Pro Lys Gln Glu Gln Ser Gln Thr Thr Thr Glu Ser Thr Thr Pro
115 120 125Lys Thr Lys Val Thr Thr Pro Pro Ser Thr Asn Thr Pro Gln Pro Met
130 135 140Gln Ser Thr Lys Ser Asp Thr Pro Gln Ser Pro Thr Ile Lys Gln Ala145 150 155 160Gln Thr Asp Met Thr Pro Lys Tyr Glu Asp Leu Arg Ala Tyr Tyr Thr
165 170 175Lys Pro Ser Phe Glu Phe Glu Lys Gln Phe Gly Phe Met Leu Lys Pro
180 185 190Trp Thr Thr Val Arg Phe Met Asn Val Ile Pro Asn Arg Phe Ile Tyr
195 200 205Lys Ile Ala Leu Val Gly Lys Asp Glu Lys Lys Tyr Lys Asp Gly Pro
210 215 220Tyr Asp Asn Ile Asp Val Phe Ile Val Leu Glu Asp Asn Lys Tyr Gln225 230 235 240Leu Lys Lys Tyr Ser Val Gly Gly Ile Thr Lys Thr Asn Ser Lys Lys
245 250 255Val Asn His Lys Val Glu Leu Ser Ile Thr Lys Lys Asp Asn Gln Gly
260 265 270Met Ile Ser Arg Asp Val Ser Glu Tyr Met Ile Thr Lys Glu Glu Ile
275 280 285Ser Leu Lys Glu Leu Asp Phe Lys Leu Arg Lys Gln Leu Ile Glu Lys
290 295 300His Asn Leu Tyr Gly Asn Met Gly Ser Gly Thr Ile Val Ile Lys Met305 310 315 320Lys Asn Gly Gly Lys Tyr Thr Phe Glu Leu His Lys Lys Leu Gln Glu
325 330 335His Arg Met Ala Asp Val Ile Asp Gly Thr Asn Ile Asp Asn Ile Glu
340 345 350Val Asn Ile Lys
355<210>32<211>313<212>PRT<213>Staphylococcus aureus<400>32Met Glu His Thr Thr Met Lys Ile Thr Thr Ile Ala Lys Thr Ser Leu1 5 10 15Ala Leu Gly Leu Leu Thr Thr Gly Val Ile Thr Thr Thr Thr Gln Ala
20 25 30Ala Asn Ala Thr Thr Leu Ser Ser Thr Lys Val Glu Ala Pro Gln Ser
35 40 45Thr Pro Pro Ser Thr Lys Ile Glu Ala Pro Gln Ser Lys Pro Asn Ala
50 55 60Thr Thr Pro Pro Ser Thr Lys Val Glu Ala Pro Gln Gln Thr Ala Asn65 70 75 80Ala Thr Thr Pro Pro Ser Thr Lys Val Thr Thr Pro Pro Ser Thr Asn
85 90 95Thr Pro Gln Pro Met Gln Ser Thr Lys Ser Asp Thr Pro Gln Ser Pro
100 105 110Thr Thr Lys Gln Val Pro Thr Glu Ile Asn Pro Lys Phe Lys Asp Leu
115 120 125Arg Ala Tyr Tyr Thr Lys Pro Ser Leu Glu Phe Lys Asn Glu Ile Gly
130 135 140Ile Ile Leu Lys Lys Trp Thr Thr Ile Arg Phe Met Asn Val Val Pro145 150 155 160Asp Tyr Phe Ile Tyr Lys Ile Ala Leu Val Gly Lys Asp Asp Lys Lys
165 170 175Tyr Gly Glu Gly Val His Arg Asn Val Asp Val Phe Val Val Leu Glu
180 185 190Glu Asn Asn Tyr Asn Leu Glu Lys Tyr Ser Val Gly Gly Ile Thr Lys
195 200 205Ser Asn Ser Lys Lys Val Asp His Lys Ala Gly Val Arg Ile Thr Lys
210 215 220Glu Asp Asn Lys Gly Thr Ile Ser His Asp Val Ser Glu Phe Lys Ile225 230 235 240Thr Lys Glu Gln Ile Ser Leu Lys Glu Leu Asp Phe Lys Leu Arg Lys
245 250 255Gln Leu Ile Glu Lys Asn Asn Leu Tyr Gly Asn Val Gly Ser Gly Lys
260 265 270Ile Val Ile Lys Met Lys Asn Gly Gly Lys Tyr Thr Phe Glu Leu His
275 280 285Lys Lys Leu Gln Glu Asn Arg Met Ala Asp Val Ile Asp Gly Thr Asn
290 295 300Ile Asp Asn Ile Glu Val Asn Ile Lys305 310
Claims (49)
1.包含一个DNA序列的分离的核酸分子，所述DNA序列选自由以下所构成的组：
(i)SEQ ID NO：1-13中所示的DNA序列；
(ii)与上述(i)中确定的SEQ ID NO：1-13所示序列杂交并编码由一种病原微生物表达的多肽的DNA序列；和
(iii)由(i)和(ii)中所限定的DNA序列的遗传密码所导致的简并的DNA序列。
2.如权利要求1所述的分离的核酸分子，其是基因组DNA。
3.如权利要求1或2所述的分离的核酸分子，所述核酸分子在严格的杂交条件下与SEQ ID NO：1-13所示的序列退火。
4.一种载体，其包含如权利要求1-3任一项所述的核酸分子。
5.如权利要求4所述的载体，其适于重组表达由所述核酸编码的多肽。
6.如权利要求4或5所述的载体，其是一种适合原核基因表达的表达载体。
7.如权利要求4或5所述的载体，其中所述载体是一种适合真核基因表达的表达载体。
8.如权利要求4至7任一项所述的载体，其中载体的适用性包括提供启动子序列。
9.如权利要求8所述的载体，其中启动子序列提供细胞特异性的，可诱导的或组成性的表达。
10.一种鉴别抗原多肽的方法，包括：
(i)提供一个核酸文库，其编码一种病原微生物的基因或部分基因序列；
(ii)转化/转染所述文库到一种宿主细胞中；
(iii)将由所述基因/部分基因序列表达的多肽与从感染或曾经感染所述病原微生物的动物得到的自体抗血清接触；和
(iv)纯化编码与所述自身抗血清结合的多肽或部分多肽的核酸。
11.如权利要求10所述的方法，其中所述文库包含一种病原微生物的基因组DNA。
12.如权利要求10或11所述的方法，其中所述病原微生物是细菌。
13.如权利要求10至12任何一项所述的方法，其中所述细菌微生物选自以下：金黄色葡萄球菌；表皮葡萄球菌；粪肠球菌；结核分枝杆菌；B族链球菌；肺炎链球菌；幽门螺杆菌；淋病奈瑟氏球菌；A族链球菌；布氏疏螺旋体；粗球孢菌；荚膜组织胞浆菌；B型脑膜炎奈瑟氏球菌；弗氏志贺氏菌；大肠杆菌；流感嗜血菌。
14.如权利要求13所述的方法，其中所述病原微生物是金黄色葡萄球菌。
15.如权利要求13所述的方法，其中所述病原微生物是表皮葡萄球菌。
16.如权利要求10至15任何一项所述的方法，其中所述核酸文库是λ文库。
17.由如权利要求10至16任何一项所述的方法鉴定的多肽。
18.如权利要求17所述的多肽，其选自由SEQ ID NO：14-19组成的组中。
19.一种制备如权利要求17或18所述多肽的方法，包括：
(i)提供一种细胞及细胞培养条件，所述细胞被权利要求4至9任何一项所述的载体转化/转染；和
(ii)从所述细胞中或其生长环境中纯化所述多肽。
20.如权利要求19所述的方法，其中所述载体编码并因此为所述重组多肽提供一种促进所述多肽纯化的分泌信号。
21.由权利要求4至9任何一项所述的载体转化或转染的细胞。
22.如权利要求21所述的细胞，其是一种原核细胞。
23.如权利要求21所述的细胞，其是选自真菌细胞、昆虫细胞、两栖动物细胞、哺乳动物细胞、植物细胞的一种真核细胞。
24.一种含有权利要求16或17所述的至少一种多肽的疫苗。
25.权利要求24所述的疫苗，其进一步包含一种载体和/或佐剂。
26.一种免疫动物抵抗一种病原微生物的方法，所述方法包含给该动物施用前述任一权利要求所述的至少一种多肽或其一部分，或前述任一权利要求所述的疫苗。
27.如权利要求26所述的方法，其中所述动物是人。
28.如权利要求26或27所述的方法，其中所述疫苗或抗原多肽是通过直接静脉注射，肌肉内注射或皮下注射给予的。
29.如权利要求25或26所述的方法，其中所述疫苗或抗原多肽是口服给予的。
30.如权利要求26至29任何一项所述的方法，其中所述疫苗是抵抗葡萄球菌属细菌的疫苗。
31.如权利要求30所述的方法，其中所述疫苗是抵抗金黄色葡萄球菌的疫苗。
32.如权利要求30所述的方法，其中所述疫苗是抵抗表皮葡萄球菌的疫苗。
33.一种抗体或至少是其一个有效部分，其至少结合权利要求16或17所述的多肽的一个选择部分。
34.如权利要求33所述的抗体，其是一种单克隆抗体。
35.如权利要求33或34所述的抗体，其中所述的有效部分包括Fab片段。
36.如权利要求33至35任何一项所述的抗体，其是一种嵌合抗体。
37.如权利要求33至35任何一项所述的抗体，其是一种人源化抗体。
38.如权利要求33至37任何一项所述的抗体，其中所述抗体被提供一种标志，标记或标签。
39.如权利要求38所述的抗体，其中所述抗体被提供一种选自放射性标记，荧光标记，附加表位的标志。
40.权利要求34至39任何一项所述的抗体，所述抗体以融合多肽的形式产生。
41.一种适合于表达权利要求34至40任何一项所述的抗体的载体。
42.一种用权利要求41所述的载体转化或转染的细胞。
43.一种生产权利要求34或40所述的抗体的方法，包括：
i)提供一种用权利要求41所述的载体转化或转染的细胞及细胞培养条件；和
ii)从所述细胞或其生长环境中纯化所述抗体。
44.一种产生权利要求34所述的抗体的杂交瘤细胞系。
45.权利要求33至40任何一项所述的抗体在制备用于治疗与金黄色葡萄球菌相关的败血症、食物中毒或皮肤损害的药物中的用途。
46.权利要求33至40任何一项所述的抗体在制备用于治疗与表皮葡萄球菌相关的败血症、腹膜炎或心内膜炎的药物中的用途。
47.制备一种产生权利要求34所述的单克隆抗体的杂交瘤细胞系的方法，其步骤包括：
i)用一种免疫原免疫一种有免疫活性的哺乳动物，所述免疫原包含至少一种具有SEQ ID NO：14-19的氨基酸序列的多肽或其片段；
ii)将被免疫的具有免疫活性的哺乳动物的淋巴细胞与骨髓瘤细胞融合形成杂交瘤细胞；
iii)筛选由步骤(ii)中的杂交瘤细胞产生的、具有结合(i)中氨基酸序列的活性的单克隆抗体；
iv)培养杂交瘤细胞使其增殖和/或分泌所述单克隆抗体；和
v)从培养上清液中回收单克隆抗体。
48.权利要求47所述的方法，其中所述免疫活性哺乳动物是小鼠。
49.权利要求47所述的方法，其中所述免疫活性哺乳动物是大鼠。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0014907.0 | 2000-06-20 | ||
| GBGB0014907.0A GB0014907D0 (en) | 2000-06-20 | 2000-06-20 | Antigenic polypeptides |
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| Application Number | Title | Priority Date | Filing Date |
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| CN2010105100192A Division CN102021184A (zh) | 2000-06-20 | 2001-06-20 | 抗原多肽 |
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| Publication Number | Publication Date |
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| CN1437653A true CN1437653A (zh) | 2003-08-20 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN2010105100192A Pending CN102021184A (zh) | 2000-06-20 | 2001-06-20 | 抗原多肽 |
| CN01811545A Pending CN1437653A (zh) | 2000-06-20 | 2001-06-20 | 抗原多肽 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN2010105100192A Pending CN102021184A (zh) | 2000-06-20 | 2001-06-20 | 抗原多肽 |
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|---|---|
| US (3) | US20030186275A1 (zh) |
| EP (4) | EP2287316A1 (zh) |
| JP (2) | JP2004500883A (zh) |
| CN (2) | CN102021184A (zh) |
| AT (2) | ATE524194T1 (zh) |
| AU (4) | AU2001274248B2 (zh) |
| BR (1) | BR0111823A (zh) |
| CA (2) | CA2805216A1 (zh) |
| DE (1) | DE60132893T2 (zh) |
| GB (1) | GB0014907D0 (zh) |
| HK (1) | HK1051873A1 (zh) |
| NO (1) | NO20025838L (zh) |
| WO (1) | WO2001098499A1 (zh) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102695724A (zh) * | 2009-05-18 | 2012-09-26 | 维尔茨堡尤利乌斯·马克西米利安大学 | 指向金黄葡萄球菌表位isaa或isab的抗体或其片段 |
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| AT410798B (de) * | 2001-01-26 | 2003-07-25 | Cistem Biotechnologies Gmbh | Verfahren zur identifizierung, isolierung und herstellung von antigenen gegen ein spezifisches pathogen |
| GB0107661D0 (en) | 2001-03-27 | 2001-05-16 | Chiron Spa | Staphylococcus aureus |
| WO2002102829A2 (en) * | 2001-06-15 | 2002-12-27 | Inhibitex, Inc. | Cross-reactive monoclonal and polyclonal antibodies which recognize surface proteins from coagulase-negative staphylococci and staphylococcus aureus |
| ATE542829T1 (de) * | 2001-08-02 | 2012-02-15 | Univ Sheffield | Impfstoff |
| AU2003254555A1 (en) * | 2002-07-26 | 2004-02-23 | Intercell Ag | S. aureus antigene |
| EP1622933A2 (en) * | 2003-04-22 | 2006-02-08 | Intercell AG | H. pylori antigens |
| PT1651166E (pt) * | 2003-07-24 | 2010-04-23 | Merck Sharp & Dohme | Polipeptidos para indução de uma resposta imunitária de protecção contra staphylococcus aureus |
| AU2005214061B2 (en) * | 2004-02-18 | 2010-02-04 | Merck Sharp & Dohme Corp. | Polypeptides for inducing a protective immune response against Staphylococcus aureus |
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| KR100871330B1 (ko) * | 1998-08-31 | 2008-12-01 | 더 프로보스트 펠로우스 앤드 스콜라스 오브 더 칼리지 오브 더 홀리 앤드 언디바이디드 트리니티 오브 퀸 엘리자베스 니어 더블린 | 응고효소 음성 포도상구균 유래의 폴리펩타이드 및폴리뉴클레오타이드 |
| GB0107661D0 (en) * | 2001-03-27 | 2001-05-16 | Chiron Spa | Staphylococcus aureus |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102695724A (zh) * | 2009-05-18 | 2012-09-26 | 维尔茨堡尤利乌斯·马克西米利安大学 | 指向金黄葡萄球菌表位isaa或isab的抗体或其片段 |
| CN102695724B (zh) * | 2009-05-18 | 2016-08-24 | 维尔茨堡尤利乌斯·马克西米利安大学 | 指向金黄葡萄球菌表位isaa或isab的抗体或其片段 |
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