CN115720521A - 用于预防金黄色葡萄球菌感染的组合物和方法 - Google Patents

Abstract

本发明涉及包含至少一种金黄色葡萄球菌(Staphylococcus aureus)抗原的免疫原性组合物，其中所述抗原是与SEQ ID NO：8的SdrH样多肽、SEQ ID NO：4的Nuc或SEQ ID NO：12的LukG具有至少80％同一性的多肽，包含与所述抗原中的至少一种选择性结合的多克隆抗体的免疫治疗组合物以及鉴定赋予受试者针对金黄色葡萄球菌引起的疾病的保护作用的抗原的体外方法。

Description

用于预防金黄色葡萄球菌感染的组合物和方法

技术领域

本发明涉及包含金黄色葡萄球菌(Staphylococcus aureus)抗原的免疫原性组合物。本发明还涉及免疫原性组合物用于赋予受试者针对金黄色葡萄球菌引起的疾病的保护作用的用途。

金黄色葡萄球菌是人感染的主要原因，导致多种病理，包括皮肤和软组织感染、骨髓炎、心内膜炎和败血症。特别是，金黄色葡萄球菌是与外来装置(例如，导管)和植入物(例如，假体)相关的大部分感染的原因，因为金黄色葡萄球菌能够在这些材料的表面形成生物膜。因为这些感染可能是慢性的或全身性的，在某些情况下会导致假体关节感染、植入失败甚至死亡，所以这些感染问题特别严重。例如，对一家大型血液透析中心的金黄色葡萄球菌感染进行的回顾性分析发现，在血液透析患者中金黄色葡萄球菌感染率接近18％，并且与10％的死亡率相关，其中绝大多数感染与血管导管相关(Fitzgerald等人，2011年)。

虽然金黄色葡萄球菌感染通常用抗生素疗法进行治疗，但出现了耐抗生素的金黄色葡萄球菌(包括耐甲氧西林(MRSA)和耐万古霉素(VRSA)的菌株)，使得传统抗生素的使用变得复杂。此外，虽然万古霉素目前是治疗MRSA菌血症和心内膜炎的金标准，但由于万古霉素组织穿透性差、不良副作用和杀菌活性慢，所以这种抗生素并不理想(Gould，2008)。在骨科植入物的情况下，最常需要进行再次手术(revision surgery)(Darouiche，2004)。然而，这种策略成本高且具有侵入性，以及通常在技术上比最初的植入手术更难，需要更大范围的手术，并且与受试者较低的生活质量结果相关。

预防金黄色葡萄球菌感染的有效疫苗的开发代表了一种对当前治疗方法的有希望替代方案，目前各种针对金黄色葡萄球菌的疫苗正在I、II或III期临床试验中进行评价，尽管尚未有成功的III期试验完成。迄今为止，疫苗开发主要集中在金黄色葡萄球菌分泌的α毒素(Hla)和/或荚膜多糖上。虽然靶向α毒素的疫苗已被证明对感染具有保护作用，其中该毒素负责大部分致病作用(例如，肺炎，描述于Bubeck和Schneewind，2008)，但该疫苗还不足以预防亚-致死感染(Adlam等，1977)。此外，鉴于荚膜多糖的可变性，以及大量的耐甲氧西林的金黄色葡萄球菌菌株是无荚膜的事实，仅有荚膜多糖的用途是受限的。各种单独或组合的金黄色葡萄球菌蛋白质也在评估中，包括IsdB蛋白质，其被证明可以在患有金黄色葡萄球菌感染的受试者中诱导抗体，尽管这不足以提供针对未来感染的保护作用(Zorman等人，2013)。临床试验进一步表明，与安慰剂接受者相比，接种IsdB疫苗没有效果，在某些情况下甚至是有害的(McNeely等人，2014年)。

由于目前的策略不能令人满意，因此仍然需要改进的免疫原性组合物，其包含金黄色葡萄球菌抗原或针对所述抗原产生的多克隆抗体。特别地，需要能够预防和/或治疗金黄色葡萄球菌感染的新型免疫原性和免疫治疗组合物，例如，其包含能够诱导针对金黄色葡萄球菌感染的保护性抗体的抗原或包含此类抗体本身。还需要新的方法来鉴定赋予受试者针对金黄色葡萄球菌引起的疾病的保护作用的抗原。特别是，鉴于临床试验的高成本和持续时间，需要一种可以用作与保护作用相关(correlate of protection)的改进的测定法，用于评估疫苗反应。

本发明通过提供免疫原性组合物、免疫治疗组合物和体外鉴定抗原的方法来满足这些和其他需要，所述抗原赋予受试者针对金黄色葡萄球菌引起的疾病的保护作用。

特别地，本发明提供了包含至少一种金黄色葡萄球菌抗原的免疫原性组合物，其中所述抗原是与SEQ ID NO：8的SdrH样多肽、SEQ ID NO：4的Nuc或SEQ ID NO：12的LukG具有至少80％同一性的多肽。

根据一个特定的方面，免疫原性组合物包含与SEQ ID NO：8的SdrH样多肽具有至少80％同一性的抗原和与SEQ ID NO：12的LukG具有至少80％同一性的抗原。

与现有抗原(如IsdB)相比，本发明的免疫原性组合物中包含的一种或多种抗原有利地提供出人意料的、改进的免疫原性特性(例如，免疫原性反应的水平、质量和/或范围)。

优选地，免疫原性组合物包含呈单独多肽形式的、或呈一种或多种融合多肽形式的、或呈单独多肽和融合多肽形式的金黄色葡萄球菌抗原。

优选地，免疫原性组合物进一步包含药学上可接受的赋形剂。

优选地，免疫原性组合物用作赋予受试者针对金黄色葡萄球菌引起的疾病的保护作用的疫苗。

本发明进一步涉及免疫治疗组合物，其包含与至少一种如本文定义的抗原选择性结合的多克隆抗体，其中所述抗体促进吞噬细胞对金黄色葡萄球菌的摄取和杀死。

优选地，免疫治疗组合物进一步包含药学上可接受的赋形剂。

优选地，免疫治疗组合物用作被动免疫治疗，以赋予受试者针对由金黄色葡萄球菌引起的疾病的保护作用。

优选地，所述金黄色葡萄球菌是耐甲氧西林金黄色葡萄球菌(MRSA)或甲氧西林易感的金黄色葡萄球菌(MSSA)。

优选地，所述受试者具有骨关节装置，优选具有骨关节植入物，更优选具有全关节置换假体。

优选地，本文提供的所述免疫原性或免疫治疗组合物用于与一种或多种对金黄色葡萄球菌感染有效的抗生素联合使用。

本发明进一步涉及鉴定抗原的体外方法，所述抗原赋予受试者针对金黄色葡萄球菌引起的疾病的保护作用，所述方法包括：

a)将包含金黄色葡萄球菌的溶液与包含针对金黄色葡萄球菌抗原产生的抗体的溶液一起孵育，优选在35℃下孵育1小时，从而获得混合悬浮液，

b)使巨噬细胞与步骤a)的混合悬浮液接触，

c)从巨噬细胞中去除混合悬浮液并添加补充有抗生素的新鲜培养基以杀死细胞外的金黄色葡萄球菌细菌，和

d)评估所述巨噬细胞对金黄色葡萄球菌细菌的内化和杀死，其中当所述抗原诱导对金黄色葡萄球菌的内化和杀死增加同时保留了巨噬细胞的活力时，所述抗原视为赋予了针对金黄色葡萄球菌引起的疾病的保护作用。

与之前的方法(其尤其使用多形核嗜中性粒细胞)相比，本发明人开发了新的OPA测定法，用于鉴定能够产生促进对金黄色葡萄球菌的摄取和杀死的抗体的目标疫苗抗原。事实上，多形核嗜中性粒细胞显示出非常强的杀菌活性(“杀死”)，这尤其使得其无法评价最终是否产生了“促进”抗体(即，其促进细菌的摄取，但随后导致细菌在细胞内生长而不是被杀死)。有利地，巨噬细胞具有比多形核嗜中性粒细胞低得多的杀菌(“杀死”)活性，因为巨噬细胞具有较低的活性氧合成和抗微生物肽的水平。此外，在骨关节假体感染的特定背景下，开发基于巨噬细胞的测定法特别有利，因为在感染的病理生理学中，循环的血液中传播的金黄色葡萄球菌必须通过脾脏和/或肺中存在的巨噬细胞从血流中清除，而不是通过多形核嗜中性粒细胞清除，从而减少菌血症的持续时间和建立假体感染的可能性。

优选地，所述巨噬细胞是永生化巨噬细胞系，优选是J774.2细胞系。

优选地，通过将在步骤c)之后3小时的内化在巨噬细胞中的细菌量与在步骤c)之后6小时的内化在巨噬细胞中的细菌量进行比较，以在步骤d)中评估对金黄色葡萄球菌细菌的杀死。

具体实施方式

在更详细地描述本发明之前，应当注意的是，除非上下文另有说明，本文所用的术语“一(a)”和“一种(an)”在其表示所提及化合物或步骤的“至少一个”、“至少第一个”、“一个或更多个”或“多个”的意义上使用。本文所用的术语“和/或”包括“和”、“或”和“由所述术语连接的元件的所有或任何其他组合”的含义。术语“包含(comprising)”、“具有(having)”、“包括(including)”或“含有(containing)”(以及任何形式的所述术语，例如，如“包含(contains)”或“含有(contain)”)是开放式的，不排除额外的、未列举的元件或方法步骤。相反，本文使用的术语“由……组成”不包括任何其他组分(超出痕量级)或步骤。

如上所述，根据第一方面，本发明涉及包含至少一种金黄色葡萄球菌抗原的免疫原性组合物，其中所述抗原是与SEQ ID NO：8的SdrH样多肽、SEQ ID NO：4的Nuc或SEQ IDNO：12的LukG具有至少80％同一性的多肽。

如本文所用，术语“免疫原性的”是指组合物在已引入具有免疫原性的组分的受试者中诱导或刺激可测量的B细胞介导的免疫反应的能力。例如，在本发明的组合物能够在受试者中诱导或刺激免疫反应的意义上说，本发明的组合物是免疫原型的，所述免疫反应可以是先天的和/或特异性的(即，针对包含在所述免疫原性组合物中的至少一种金黄色葡萄球菌多肽)、体液的和/或细胞的(例如，抗体和/或细胞因子的产生和/或细胞毒性T细胞，B、T淋巴细胞，抗原提呈细胞，辅助T细胞，树突细胞，NK细胞等的活化)。免疫原性组合物通常在施用的受试者中产生保护性反应。具体而言，本发明的组合物是免疫原性的，因为其诱导识别至少一种金黄色葡萄球菌多肽的抗体，增加吞噬细胞对金黄色葡萄球菌的摄取和杀死。然而，所述组合物还可以诱导一种或多种额外的免疫反应。

具体而言，发明人在此出人意料地表明，SdrH样多肽、Nuc和LukG抗原中的每一个都能够诱导增加吞噬细胞对金黄色葡萄球菌的摄取和杀死的抗体。在本文中在基于巨噬细胞的模型中首次产生具有这种活性的抗体，表明当本文所述的抗原存在于免疫原性组合物中时诱导出针对金黄色葡萄球菌感染的保护作用。实际上，此处使用本发明的抗原获得的结果与使用IsdB获得的结果(之前显示具有有害影响(因为可能有利于金黄色葡萄球菌感染))形成显著对比，证实这种基于巨噬细胞的模型在评估抗原时的针对性(pertinence)。在动物模型中获得的体内结果进一步显示，与单独使用佐剂和/或使用对照抗原(如葡萄球菌激酶)所观察到的相比，这些抗原能够在更大程度上减少肾脏中的金黄色葡萄球菌的细菌生长，这进一步证实这些抗原有能力诱导针对金黄色葡萄球菌感染的保护作用。因此，根据一个特定方面，免疫原性组合物包含至少一种金黄色葡萄球菌抗原，其诱导针对所述抗原的抗体，所述抗体增加通过细菌的吞噬作用对金黄色葡萄球菌的摄取和杀死，其中所述抗原是与SEQ ID NO：8的SdrH样多肽、SEQ ID NO：4的Nuc或SEQ ID NO：12的LukG具有至少80％同一性的多肽。

如本文所用，术语“金黄色葡萄球菌抗原”是指存在于金黄色葡萄球菌物种中、或从金黄色葡萄球菌物种中获得的多肽，或其能够被抗体结合的片段(例如，表位)，其中所述抗原选自“SdrH样”多肽、Nuc和LukG以及其一种或多种的组合。通常，这种抗原含有一个或多个B表位。在本发明的上下文中，该术语涵盖天然的金黄色葡萄球菌抗原(例如，全长抗原)或其修饰的形式(例如，片段或变体)。尤其可以从自然界中的金黄色葡萄球菌来源中发现、分离和获得“天然”的金黄色葡萄球菌抗原。此类来源包括从已感染或曾暴露于金黄色葡萄球菌的受试者中收集的生物样品(例如，血液、血浆、血清、唾液、痰、组织切片、活检标本等)、培养细胞以及在保藏机构(例如，ATCC或TB机构)、文库可获得的、或文献中描述的重组材料(例如，金黄色葡萄球菌分离株、金黄色葡萄球菌基因组等)。

“SdrH样”抗原或多肽是细胞壁锚定的丝氨酸-天冬氨酸重复家族蛋白质，其含有宿主附着结构域MSCRAMM(识别粘附基质分子的微生物表面成分(microbial surfacecomponents recognizing adhesive matrix molecules))。“SdrH样”多肽可以包含SEQ IDNO：7或8的序列，其分别可以由SEQ ID NO：5或6的核苷酸序列编码。在本发明的上下文中，“SdrH样”多肽优选具有SEQ ID NO：8的序列。

“Nuc”抗原(也称为微球菌核酸酶或热核酸酶)是一种细胞外核酸酶。在细胞膜上被信号肽酶切割后，Nuc可以加工成两种活性形式：NucA或NucB。Nuc可以尤其包含SEQ IDNO：3或4的序列，其可以由SEQ ID NO：1或2的核苷酸序列编码。在本发明的上下文中，Nuc优选具有SEQ ID NO：4的序列。

“LukG”抗原(也称为LukA)与“LukH”(也称为LukB)形成异二聚体。这种异二聚体LukGH是一种形成孔的杀白细胞素，其至少部分介导金黄色葡萄球菌杀死免疫细胞，例如人类单核细胞、巨噬细胞和多形核细胞。LukG可以包含SEQ ID NO：11或12的序列，其分别可以由SEQ ID NO：9或10的核苷酸序列编码。在本发明的上下文中，LukG优选具有SEQ ID NO：12的序列。

虽然LukG与LukH形成异二聚体，优选地所述免疫原性组合物包含LukG而不存在LukH。事实上，本发明人惊奇地发现，当单独使用LukG时(即，在没有LukH的情况下)，LukG可以诱导增加吞噬细胞对金黄色葡萄球菌的摄取和杀死的抗体。这与之前的研究完全相反，之前的研究表明必须使用LukGH异二聚体以产生抗体。特别是，Badarau等人，2016年发现，针对单独的LukG或LukH产生的单克隆抗体几乎没有、甚至没有中和LukGH毒素的能力。因此，根据一个优选的方面，虽然免疫原性组合物可以既包含LukG又包含LukH，但其优选包含LukG而不包含LukH。

技术人员将理解，由于遗传密码的简并性，有许多核苷酸序列可以编码如本文所述的多肽。特别地，给定核苷酸序列内的密码子使用可以适应于在金黄色葡萄球菌以外的生物(例如，大肠杆菌)中优化表达相应多肽。

修饰的金黄色葡萄球菌抗原(例如，变体)通常在一个或多个位置不同于本文具体公开的多肽或天然多肽，例如通过一个或多个氨基酸取代、插入、添加和/或缺失、非天然排列以及其任何组合。氨基酸取代可以是等效的或不等效的。优选地，取代是用“等效”氨基酸进行的，即结构与原始氨基酸相似的任何氨基酸，因此不太可能改变抗原的生物活性。下表1中列出了此类取代的示例：

表1.使用等效氨基酸的取代

当考虑到有几种修饰时，所述修饰可能涉及连续和/或不连续的残基。修饰可以通过本领域技术人员已知的多种方式产生，例如定点诱变、PCR诱变、DNA改组和通过合成技术(例如，产生编码所需多肽变体的合成核酸分子)。

无论金黄色葡萄球菌抗原的来源(例如，天然的或修饰的)如何，本发明的免疫原性组合物中包含的抗原保留了相应天然抗原(更优选B表位)的一个或多个免疫原性部分。鉴定抗原的合适的免疫原性部分的方法是本领域公知的。

如本文所用，术语“多肽”是指氨基酸残基的聚合物，其包含通过共价肽键键合的至少10个或更多个氨基酸，优选至少20个或更多个氨基酸。多肽可以是线性的、分支的或环状的以及可以包含天然存在的和/或氨基酸类似物。多肽可以被化学修饰(例如，被糖基化、脂化、乙酰化、切割、通过二硫键桥交联和/或磷酸化的)。多肽可以包含额外的元件，例如标签(例如，his、myc、Flag等)和/或靶向肽(例如，信号肽、跨膜结构域等)。优选地，本发明的免疫原性组合物中包含的至少一种多肽不包含信号肽。优选地，本发明的免疫原性组合物中包含的至少一种多肽不包含标签。应当理解，术语“多肽”涵盖蛋白质(通常用于包含50个或更多个氨基酸残基的多肽)、寡肽和肽(通常用于包含少于50个氨基酸残基的多肽)。因此，每种多肽可以由特定氨基酸表征并由特定核酸序列编码，例如本文提供的核酸序列。

因此，当氨基酸序列是多肽的最终氨基酸序列的一部分时，多肽“包含”氨基酸序列。这种多肽在某些情况下可以具有多达数百个额外的氨基酸残基(例如，标签肽、靶向肽等)。当多肽不包含除所述氨基酸序列之外的任何氨基酸时，多肽“由”所述氨基酸序列“组成”。

术语“百分比(％)同一性”是指两个多肽或核酸分子之间的氨基酸与氨基酸的对应性、或核苷酸与核苷酸的对应性。两个分子之间的同一性的百分比是序列共有的相同位置的数量的函数，考虑了为了最佳比对而必须引入的空位数量和每个空位的长度。本发明上下文中所指的百分比同一性是在待比较的序列进行最佳比对之后确定的，其因此可以包含一个或多个插入、缺失、截短和/或取代。可以通过本领域技术人员公知的任何序列分析方法计算出该百分比同一性。特别地，百分比同一性可以在待比较序列的全长上对其整体进行全局比对之后确定。除了手动比较之外，还可以使用Needleman和Wunsch(1970)的算法确定全局比对。

对于核苷酸序列，可以使用本领域技术人员公知的任何软件进行序列比较，例如Needle软件。使用的参数可以主要如下：“空位开放”等于10.0，“空位延伸”等于0.5以及EDNAFULL矩阵(NCBI EMBOSS版本NUC4.4)。

对于氨基酸序列，可以使用本领域技术人员公知的任何软件进行序列比较，例如Needle软件。使用的参数可以主要如下：“空位开放”等于10.0、“空位延伸”等于0.5以及BLOSUM62矩阵。

优选地，在本发明的上下文中限定的百分比同一性通过将序列在其全长上进行比较的全局比对来确定。

本发明涵盖与本文公开的多肽具有基本序列同一性的多肽序列，优选包括使用上述方法与本文提供的多肽序列具有至少50％的序列同一性，优选至少60％、70％、75％、80％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％或更高的序列同一性。根据一个优选的实施方案，该多肽与金黄色葡萄球菌亚种的金黄色葡萄球菌Mu50(登录号BA000017.4)的SdrH样多肽、Nuc或LukG具有至少80％的同一性。优选地，该多肽与SEQ ID NO：8的SdrH样多肽、SEQ ID NO：4的Nuc或SEQ ID NO：12的LukG具有至少80％的同一性，甚至更优选具有至少85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或更高的同一性。优选地，该多肽与SEQ ID NO：8的SdrH样多肽、SEQ ID NO：4的Nuc或SEQ ID NO：12的LukG具有100％的同一性。

本文提供的免疫原性组合物可以包含本文提供的多肽的任何组合。作为一个非限制性示例，该组合物可以包含与SEQ ID NO：4的Nuc具有至少80％同一性的多肽和与SEQ IDNO：12的LukG具有至少80％同一性的多肽。或者，该组合物可以包含与SEQ ID NO：4的Nuc具有至少80％同一性的多肽和与SEQ ID NO：8的SdrH样多肽具有至少80％同一性的多肽。或者，该组合物可以包含与SEQ ID NO：8的SdrH样多肽具有至少80％同一性的多肽和与SEQID NO：12的LukG具有至少80％同一性的抗原。或者，该组合物可以包含与SEQ ID NO：4的Nuc具有至少80％同一性的多肽、与SEQ ID NO：12的LukG具有至少80％同一性的多肽以及与SEQ ID NO：8的SdrH样多肽具有至少80％同一性的多肽。优选地，免疫原性组合物包含与SEQ ID NO：8的SdrH样多肽具有至少80％同一性的抗原和与SEQ ID NO：12的LukG具有至少80％同一性的抗原。

本文提供的抗原有利地诱导增加吞噬细胞对金黄色葡萄球菌的摄取和杀死的抗体。因此，本发明的免疫原性组合物有利地包含至少一种金黄色葡萄球菌抗原，其诱导增加吞噬细胞对金黄色葡萄球菌的摄取和杀死的抗体，其中所述抗原是与SEQ ID NO：8的SdrH样多肽、SEQ ID NO：4的Nuc或SEQ ID NO：12的LukG具有至少80％同一性的多肽。不受理论限制，抗体可以促进金黄色葡萄球菌细菌的吞噬作用、或抗体依赖性细胞毒性(ADCC)或促进两者。在一种情况下，调理抗体的抗原结合部分与靶抗原结合，而调理抗体的Fc部分与吞噬细胞上的Fc受体结合。在其他情况下，调理抗体的抗原结合部分与靶抗原结合，而调理抗体的Fc部分与免疫效应细胞结合(例如，通过其Fc结构域)，从而触发通过结合的效应细胞(例如，单核细胞、嗜中性粒细胞和自然杀死细胞)的靶细胞裂解。

当多个多肽存在于免疫原性组合物中时，本文提供的免疫原性组合物可以包含呈单独多肽形式的、或呈一种或多种融合多肽形式的、或呈单独多肽和融合多肽形式的金黄色葡萄球菌抗原。如本文所用，术语“融合多肽”是指通过将两个或更多个多肽序列连接在一起而产生的多肽。本发明所涵盖的融合多肽包括嵌合基因构建体的翻译产物，所述嵌合基因构建体将编码一种或多种抗原或其片段或突变体的DNA序列与编码第二多肽的DNA序列连接以形成单个开放阅读框。换言之，“融合多肽”是指通过肽键或通过几种肽连接在一起的两个或更多个蛋白质的重组蛋白。

当免疫原性组合物中包含两个或更多个多肽时，本文提供的免疫原性组合物可以进一步包含相同或不同量的每种组分。作为非限制性示例，每剂可以施用总量为50μg的抗原。应当理解，所述一种或多种金黄色葡萄球菌抗原的最佳量可以由本领域技术人员确定。

本发明的另一方面是，本文提供的免疫原性组合物用于赋予受试者针对金黄色葡萄球菌引起的疾病的保护作用的疫苗的用途。所述组合物包含足量的所述一种或多种抗原以便具有治疗效果。优选地，将所述疫苗施用于不存在金黄色葡萄球菌感染的受试者，从而在所述受试者中诱导针对金黄色葡萄球菌的保护性体液或细胞免疫反应。或者，可以将所述疫苗施用于已经发生金黄色葡萄球菌感染但处于足够早期的受试者，从而使得对疫苗产生的免疫反应有效地抑制金黄色葡萄球菌感染的进一步扩散。当金黄色葡萄球菌菌血症(SAB)已经发生但尚未引起更严重的感染时(例如，血流感染(bloodstream infection)或败血症)，情况尤其如此。

所述免疫原性组合物或疫苗可以作为单一剂量施用。或者，所述免疫原性组合物或疫苗可以在一段时间内以多剂量施用。特别地，可以适当地重复施用疫苗以保持保护作用。

所述免疫原性组合物或疫苗还可以包含一种或多种佐剂，其用于增强免疫反应的幅度、质量和/或持续时间。免疫原性组合物和疫苗的佐剂是本领域公知的。作为非限制性示例，所述佐剂包括不完全或完全弗氏佐剂、单甘油酯和脂肪酸(例如，一油清(mono-olein)、油酸和大豆油的混合物)、无机盐如铝盐(例如，氢氧化铝、磷酸铝、硫酸铝)或磷酸钙凝胶、油乳液和基于表面活性剂的制剂(例如，MF59(微流体化的洗涤剂稳定的水包油乳液)、QS21(纯化的皂苷)、AS02[SBAS2](水包油乳液+MPL+QS-21)、MPL-SE、Montanide ISA-51和ISA-720(稳定的油包水乳液))、颗粒佐剂(例如，病毒体(结合流感血凝素的单层脂质体载体)、AS04(含MPL的[SBAS4]铝盐)、ISCOMS(皂苷和脂质的结构复合物)、聚丙交酯共乙交酯(PLG))、天然和合成微生物衍生物(例如，单磷酰脂质A(MPL)、Detox(MPL+M.Phlei细胞壁骨架)、AGP[RC-529](合成酰化单糖)、Detox-PC、DC Chol(能够自组织成脂质体的类脂免疫刺激剂)、OM-174(脂质A衍生物)、CpG基序(含有免疫刺激的CpG基序的合成寡核苷酸)、提供无毒佐剂作用的遗传修饰的细菌毒素，如修饰的LT和CT)、内源性人免疫调节剂(例如，hGM-CSF或hIL-12(可以作为蛋白质或编码质粒施用的细胞因子)、Immudaptin(C3d串联阵列)、MoGM-CSF、TiterMax-G、CRL-1005、GERBU、TERamide、PSC97B、Adjumer、PG-026、GSK-I、GcMAF、B-alethine、MPC-026、Adjuvax、CpG ODN、Betafectin、矾和MF59)以及惰性载体(如金颗粒)。优选地，佐剂是无机盐，优选在上文列出的那些之中，更优选是氢氧化铝和/或磷酸铝。优选地，将佐剂配制成湿凝胶悬浮液，可购自InvivoGen的

和Adju-

佐剂是这种情况。优选地，抗原(Ag)与佐剂的比率为0.4至3的mg Ag：mg铝(Al)。

在另一方面，本发明涉及免疫治疗组合物，其包含选择性结合至少一种如本文提供的金黄色葡萄球菌抗原(例如，与SdrH样多肽、Nuc或LukG具有至少80％同一性的多肽)的抗体，其中所述抗体促进吞噬细胞对金黄色葡萄球菌的摄取和杀死。

如本文所用，表述“免疫治疗组合物”是指包含免疫分子(例如，抗体，以及任选的额外的免疫分子)并提供被动免疫的组合物。“被动免疫”更特别地指在不施用抗原的情况下赋予受试者的任何免疫力。被动免疫通常是暂时的和短期的(例如，提供数周或数月的免疫力)。

如本文所用，术语“抗体”是指至少包含抗原结合片段或抗原结合结构域并且选择性结合靶抗原的任何多肽。因此，免疫治疗组合物可以尤其包含与一种或多种金黄色葡萄球菌抗原结合的抗体或包含抗体CDR结构域的多肽。在某些情况下，尽管存在一定程度的交叉反应，但应理解与靶抗原结合的抗体仍具有选择性。通常，当结合常数K_A高于10^-6M时，抗体与抗原之间的结合视为是特异性的。包含在本文提供的免疫治疗组合物中的抗体可以是多克隆的、单克隆的、单特异性的、多特异性的、人的、人源化的、单链的、嵌合的、合成的、重组的或保留选择性抗原结合的此类抗体的任何片段，包括但不限于Fab、F(ab')₂、Fv和scFv片段。抗体可以是整个免疫球蛋白的任何类型(例如，IgG、IgE、IgM、IgD、IgA和IgY)、类别(例如，IgG₁、IgG₂、IgG₃、IgG₄、IgA₁和IgA₂)或亚类。优选地，本文提供的抗体是多克隆的。因此，根据优选的实施方案，本发明的免疫治疗组合物包含选择性结合至少一种本文提供的抗原的多克隆抗体，其中所述抗体促进吞噬细胞对金黄色葡萄球菌的摄取和杀死。

如本文所用，术语“多克隆抗体”更特别地指能够与相同或不同抗原上的几种不同特异性的抗原决定簇结合或反应的抗体分子的混合物。因此，多克隆抗体来源于不同的B细胞谱系。多克隆抗体的抗原特异性可变性位于构成多克隆抗体的各个抗体的可变区，特别是互补决定区CDR1、CDR2和CDR3。多克隆抗体可以通过使用靶抗原或其部分免疫动物(如马、牛、鸟、兔、小鼠或大鼠)，利用展示技术(例如，噬菌体、酵母或核糖体展示)或杂交瘤技术制备。多克隆抗体制剂可以从免疫动物的血液、乳汁、初乳或卵中分离出来，通常除了包含对靶抗原特异的抗体之外还包含对靶抗原不特异的抗体。可以从多克隆抗体制剂中纯化出对靶抗原特异的抗体，或者可以使用多克隆抗体制剂而无需进一步纯化。因此，本文所用的术语“多克隆抗体”既指其中已富集了特异于靶抗原的抗体的抗体制剂，也指未被纯化的制剂。多克隆抗体可以以分离的形式、溶液(例如，动物抗血清)或宿主细胞(例如，杂交瘤)提供。根据特定方面，免疫治疗组合物可以是多克隆抗血清。本领域技术人员已知许多用于富集针对特定抗原的抗体的多克隆抗体的技术。在某个方面，可以从已经用本文提供的抗原攻击过的动物或第二受试者中亲和纯化出一种或多种抗体。可以使用如WO 2004/061104中提供的适用于预防性和治疗性施用的高度特异性的多克隆抗体的重组生产，其通过全文引用并入本文。重组多克隆抗体(rpAb)可以作为单一制剂从生产的生物反应器中纯化，而无需对构成重组多克隆蛋白的各个成分进行单独处理、制造、纯化或表征。或者，在某些情况下，可以设想多克隆抗体是通过混合多种单克隆抗体来制备。

本发明的免疫治疗组合物可用于治疗目的，例如用于治疗暴露至金黄色葡萄球菌后的受试者。免疫治疗组合物也可在预期或可能暴露至金黄色葡萄球菌之前进行预防性使用(例如，在骨科手术、肾透析之前)。所述免疫治疗组合物可以有利地用于预防或治疗携带相应抗原(例如，“SdrH样”多肽、Nuc和/或LukG)的金黄色葡萄球菌菌株的感染。可以根据需要重复施用，用于在给定时间段内或在特定事件之前(例如，手术之前)提供被动免疫。

优选地，通过被动免疫发生所述感染的预防或治疗。因此，根据一个优选的实施方案，本文提供的免疫治疗组合物用作被动免疫治疗，用于赋予受试者针对由金黄色葡萄球菌引起的疾病的保护作用。在这方面，免疫治疗组合物可以是多克隆组合物。在具体的实施方案中，免疫治疗组合物是多克隆抗血清，优选是从动物亲和纯化的，所述动物已经被“SdrH样”多肽、Nuc和/或LukG抗原攻击。

优选地，本发明的包含至少一种金黄色葡萄球菌抗原的免疫原性组合物、或包含针对所述至少一种金黄色葡萄球菌抗原产生的抗体，优选多克隆抗体的免疫治疗组合物，进一步包含至少一种药学上可接受的赋形剂。术语“药学上可接受的赋形剂”在本文中定义为与药物组合物相容、不会在患者中产生不想要的副作用并且通常被视为是无毒的组分或组分的组合。药学上可接受的赋形剂最常涉及促进组合物的施用、增加产品保质期或功效，或改善组合物的溶解度或稳定性。在某些情况下，赋形剂本身也可以具有治疗作用。所述一种或多种赋形剂的选择还可以取决于所期望的施用途径。在本发明的上下文中，药学上可接受的赋形剂可以尤其包含一种或多种稀释剂、佐剂、抗氧化剂、防腐剂、缓冲剂和增溶剂。作为非限制性示例，药学上可接受的赋形剂可以包含水、盐水、磷酸盐缓冲盐水、糖(如蔗糖或右旋糖)、甘油、乙醇、丙二醇、聚山梨醇酯80、聚(乙烯)乙二醇300和400(PEG 300和400)、PEG化的蓖麻油(例如，Cremophor EL)、泊洛沙姆407和188、脂肪乳剂、脂质、PEG化的磷脂、聚合物基质、生物相容性聚合物、脂质球、囊泡、脂质体、玉米淀粉、明胶、乳糖、蔗糖、微晶纤维素、高岭土、甘露醇、磷酸二钙、硫酸钙、氯化钠、海藻酸、交联羧甲基纤维素钠、羟基乙酸淀粉钠及其组合。

用于制备含有抗原(即多肽)的免疫原性组合物、或含有抗体作为活性成分的免疫治疗组合物的方法在本领域中也是公知的。制剂可包括适用于鼻、局部、口服(包括颊和舌下)和/或肠胃外施用的那些。制剂可以方便地以单位剂型存在。可以与载体材料组合以产生单一剂型的活性成分的量可以根据受试者和/或特定的施用方式而变化。可以与载体材料组合以产生单一剂型的活性成分的量将通常是产生治疗效果的化合物的量。通常，此类组合物被制备为可注射的(作为液体溶液或悬浮液)，然而也可以制备为在注射前适于溶解或悬浮在液体中的固体形式。该制剂也可以是乳化的。活性成分通常与赋形剂混合，如以上列出的一种或多种。

如本文所用，术语“金黄色葡萄球菌”是指金黄色葡萄球菌种的任何菌株。该术语涵盖实验室菌株以及临床分离株。根据优选的实施方案，金黄色葡萄球菌对一种或多种抗生素具有耐药性，优选是耐甲氧西林的金黄色葡萄球菌(MRSA)。术语“耐甲氧西林”是指细菌菌株对甲氧西林的杀菌作用缺乏易感性。通常位于葡萄球菌染色体盒(StaphylococcalChromosomal Cassette)(SCC)内的mecA或mecC基因尤其赋予对甲氧西林的耐药性。MRSA菌株也对可能除了所谓的“第五代头孢菌素”之外的所有β内酰胺类试剂具有天然耐药性，在第五代头孢菌素中头孢洛林和头孢比普罗是首选的可用试剂。MRSA菌株还可以包含对其他抗生素(例如，糖肽、脂肽、莫匹罗星、喹诺酮类、氨基糖苷类、大环内酯类、利福平等)的耐药性。或者，金黄色葡萄球菌可以是对甲氧西林敏感的金黄色葡萄球菌(MSSA)。对甲氧西林敏感的菌株易感于甲氧西林和其他不被金黄色葡萄球菌中常见的A类β内酰胺酶水解的β内酰胺(尤其是苯甲异噁唑青霉素、邻氯青霉素、萘夫西林、头孢菌素、碳青霉烯类、青霉素/β内酰胺抑制剂组合)的杀菌作用，但可以包含对其他抗生素的耐药性。

如本文所用的表述“赋予针对金黄色葡萄球菌引起的疾病的保护作用”是指预防或延迟金黄色葡萄球菌相关疾病或感染的发作和/或建立。作为非限制性示例，所述金黄色葡萄球菌疾病或感染可以是皮肤或软组织感染(SSTI)、伤口感染、菌血症、心内膜炎、肺炎、骨髓炎、中毒性休克综合征、感染性心内膜炎、毛囊炎、疖、痈、脓疱病、大疱性脓疱病、蜂窝组织炎、葡萄球菌病(botryomyosis)、烫伤性皮肤综合征、中枢神经系统感染、感染性和炎性眼病、骨髓炎或其他关节或骨骼感染、呼吸道感染、尿路感染、化脓性关节炎、败血症或坏疽。特别地，如本文所述，所述金黄色葡萄球菌相关的疾病或感染可以与受试者中的外来装置或植入物的存在相关。

“患者”或“受试者”可以是无分年龄的任何人个体。具体而言，受试者可以是成人或儿童。术语“成人”在本文中是指至少16岁的个体。术语“儿童”包括0-1岁的婴儿和1-8岁、8-12岁和12-16岁的儿童。术语“儿童”还包括出生至28天的新生儿和28至364天的后新生儿(post-neonatal)。组合物可以施用于成人或儿童，包括新生儿。本发明的组合物特别有利地用于预防或治疗受试者中的与金黄色葡萄球菌相关的疾病，所述受试者因任何原因，更优选因心脏或骨科手术将要住院或已经住院，或将要进行或已经进行透析治疗(例如，肾透析)。在优选的实施方案中，受试者携带外来装置或植入物。作为非限制性示例，所述受试者可以携带一种或多种以下装置或植入物：静脉内导管、血管假体、血管内支架、脑脊液分流器、人工心脏瓣膜、导尿管、关节假体、骨科固定装置、心脏起搏器或除颤器、腹膜透析导管、宫内节育装置、胆道支架、胰岛素施用导管、假牙、乳房植入物、隐形眼镜或任何其他外来装置或植入物。优选地，所述受试者具有骨关节装置，优选骨关节植入物，更优选整体或部分关节假体，甚至更优选整体或部分髋关节、膝关节、肩关节、肘关节、腕关节或踝关节置换物(replacement)。

在本发明的另一方面，根据本文提供的任何实施方案的免疫原性或免疫治疗组合物用于治疗受试者的金黄色葡萄球菌感染。术语“治疗”是指改善或完全消除金黄色葡萄球菌感染症状的方法。治疗优选通过向受试者内部施用如本文所述的免疫原性或免疫治疗组合物与一种或多种常规疗法(如用于治疗或预防金黄色葡萄球菌感染的抗生素疗法)组合进行，或在因金黄色葡萄球菌感染而导致植入失败的情况下与植入物置换相伴进行。因此，根据具体实施方案，所述免疫原性或免疫治疗组合物与一种或多种对金黄色葡萄球菌感染有效的抗生素联合使用。

本发明的另一方面涉及在需要其的受试者中引发免疫反应以预防或治疗金黄色葡萄球菌感染的方法，所述方法包括提供或施用本文所述的免疫原性组合物。本发明还涉及预防和/或治疗金黄色葡萄球菌相关疾病或感染的方法，所述方法包括向需要其的受试者施用根据本文所述的任何实施方案中的免疫原性或免疫治疗组合物。根据具体实施方案，本文提供向需要其的受试者赋予被动免疫的方法，所述方法包括以下步骤：(1)使用包含至少一种金黄色葡萄球菌抗原的免疫原性组合物产生抗体制剂，其中所述抗原是与SEQID NO：8的SdrH样多肽、SEQ ID NO：4的Nuc和/或SEQ ID NO：12的LukG具有至少80％同一性的多肽；和(2)将免疫治疗制剂施用于所述受试者。

优选地，所述金黄色葡萄球菌是抗生素耐药性的金黄色葡萄球菌，更优选是MRSA。优选地，所述受试者具有如本文所述的外来装置或植入物，更优选地，所述受试者具有骨关节装置，优选骨关节植入物，更优选全关节置换假体。

本发明还包括根据本发明的免疫原性或免疫治疗组合物在制备用于提高受试者的免疫反应，优选用于预防和/或治疗金黄色葡萄球菌相关疾病或感染的药物中的用途。

本发明还包括根据本文所述的任何实施方案中的免疫原性或免疫治疗组合物在预防和/或治疗金黄色葡萄球菌相关疾病或感染中的用途。

根据另一方面，本发明涉及试剂盒，其包含如本文提供的免疫原性或免疫治疗组合物和用于向受试者提供或施用本文所述的免疫原性或免疫治疗组合物的说明书。

如上所述，鉴于临床试验的高成本和持续时间，体外调理吞噬(OPA)测定法由于与保护作用相关，通常用于评估疫苗反应(Romero-Steiner等，2006)，以及用于评价抗体功能性，特别是评价抗体促进专门的吞噬细胞对金黄色葡萄球菌的摄取的能力(Nanra等人，2013；Fowler等人，2013)。尤其是与之前的使用多形核嗜中性粒细胞的方法不同，本发明人开发了本文提供的新的OPA测定法，用于鉴定能够(产生)促进对金黄色葡萄球菌的摄取和杀死的抗体的靶疫苗抗原。

因此，根据另一方面，本发明涉及用于鉴定抗原的体外方法，所述抗原赋予受试者针对金黄色葡萄球菌引起的疾病的保护作用，所述方法包括：

a)将包含金黄色葡萄球菌的溶液与包含针对金黄色葡萄球菌抗原产生的抗体的溶液一起孵育，优选在35℃下孵育1小时，从而获得混合悬浮液，

b)使巨噬细胞与步骤a)的混合悬浮液接触，

c)从巨噬细胞中去除混合悬浮液，和

d)评估所述巨噬细胞对金黄色葡萄球菌细菌的内化和杀死，其中当所述抗原诱导对金黄色葡萄球菌的内化和杀死增加时，视为所述抗原赋予了针对金黄色葡萄球菌引起的疾病的保护作用。

上述方法的步骤a)、b)、c)和d)必须以上述顺序执行。该方法还可以进一步包括额外的步骤，如培养或稀释包含金黄色葡萄球菌的溶液使得细菌以特定密度(例如，光密度为1)提供、浓缩或稀释包含抗体的溶液和/或稀释混合溶液(例如，使得巨噬细胞可以与具有特定感染复数(MOI)的细菌接触)、洗涤细菌和/或巨噬细胞、孵育巨噬细胞等。

虽然步骤a)优选在35℃进行1小时，但孵育可以在2℃至40℃的温度范围内进行1分钟至48小时。类似地，虽然步骤b)优选在35℃下进行1小时，但巨噬细胞可以在2℃至38℃的温度范围内与混合悬浮液接触1分钟至48小时。优选地，巨噬细胞在5％CO₂的气氛中在35℃中储存。优选地，混合悬浮液的MOI在10：1至25：1之间(即每个巨噬细胞10至25个细菌)。通过离心可以增强巨噬细胞层与金黄色葡萄球菌的接触，从而促进金黄色葡萄球菌和巨噬细胞之间的接触。因此，离心可以有利地减少步骤b)的持续时间。所述接触步骤允许一定比例的金黄色葡萄球菌细菌被内化，这可以进一步根据步骤a)中提供的包含抗体的溶液的组成而变化。步骤c)中去除混合悬浮液可以尤其包括一个或多个洗涤步骤(例如，用新鲜培养基或磷酸盐缓冲盐水(PBS)洗涤巨噬细胞)。实际上，这有利地改进对外部的金黄色葡萄球菌的去除。步骤c)可以进一步包括添加包含抗生素的溶液，优选在去除混合悬浮液之后。添加这种溶液有利地确保杀死在细胞之外残留的任何金黄色葡萄球菌细菌。因此，金黄色葡萄球菌应该对使用的抗生素敏感，而巨噬细胞优选不受影响。作为一个非限制性示例，所述抗生素是庆大霉素。庆大霉素可以尤其在50μg/mL至100μg/mL浓度范围内，或在等于或高于100μg/mL的浓度中。作为非限制性示例，所述包含抗生素的溶液是细胞培养基，如DMEM。所述培养基优选是之前从未使用过的(即，其是“新鲜的”)。

因此，根据优选的实施方案，步骤c)包括从巨噬细胞中去除混合悬浮液并添加补充有抗生素的溶液。更优选地，步骤c)包括从巨噬细胞中去除混合悬浮液并添加补充有抗生素的新鲜培养基，从而确保细胞外金黄色葡萄球菌被杀死。

可以使用本领域已知的方法确定巨噬细胞中金黄色葡萄球菌的内化和杀死。

例如，根据本领域已知的方法(例如，图像分析等)，可以通过根据观察到的荧光水平对细菌进行定量以确定内化(例如，通过测量表达荧光蛋白的重组的金黄色葡萄球菌的荧光，直接地测量产生的荧光，或通过添加一种或多种染色剂至固定的、透化的巨噬细胞，例如，

FL万古霉素(VMB)(结合革兰氏阳性菌细胞壁的荧光糖肽抗生素)，间接地测量产生的荧光)。尤其可以通过比较在步骤c)之后的3h，与对照血清(例如，针对金黄色葡萄球菌中不存在的抗原(如GFP蛋白)产生的)相比，用包含针对感兴趣抗原产生的抗体的混合悬浮液处理的巨噬细胞中存在的荧光水平，使用图像采集和分析确定内化。作为一个特别的示例，图像分析可以用于确定，例如，每种条件下每个巨噬细胞的VMB荧光阳性的像素数。作为另一示例，通过将在步骤c)后3小时的内化在巨噬细胞中的细菌量与在步骤c)后6小时的内化在巨噬细胞中的细菌量进行比较，以在步骤d)中评估对金黄色葡萄球菌的杀死。具体而言，根据本文描述的方法，可以根据在3h相对6h观察到的VMB荧光水平来确定杀死。当在6h测量的荧光与3h相比增加时，可以视为发生了细菌生长。当在6h测量的荧光与3h相比减少时，视为发生细菌溶解(即杀死)。荧光的这种变化反映与细菌生长/裂解相关的细胞内肽聚糖量的变化。

该方法中使用的巨噬细胞可以是任何巨噬细胞系或分离的巨噬细胞。优选地，所述巨噬细胞在经典培养条件下(即在DMEM中)以单层培养。优选地，所述巨噬细胞是永生化巨噬细胞系，更优选是J774.2细胞系。

附图说明

图1.由免疫血清介导的对金黄色葡萄球菌的摄取

金黄色葡萄球菌的摄取(感染后3h)，感染复数(MOI)为10：1(左图)和25：1(右图)，使用1/1000(上图)和1/2000(下图)稀释的免疫血清。报告出平均荧光面积值(488nm激发，515nm发射)，通过抗GFP抗体进行归一化(值为1)。在相对于抗GFP抗体荧光进行归一化之前，从每个细胞的荧光面积值计算标准偏差。使用Graphpad Prism对原始数据评价统计显著性。*P值<0.05.**P值<0.01。测试的蛋白质：Pbp2a(“A”)、SspA(“B”)、Sak(“C”)、IsaA(“D”)、GlpQ(“E”)、自溶素样蛋白(“F”)、Nuc(“G”)、Hla(“H”)、LukG(“I”)、LukH(“J”)、IsdA(“K”)、IsdB(“M”)、SdrD(作为两个部分多肽：“N”和“Nb”)、ClfA(作为两个部分多肽：“O”和“Ob”)、MntC(“1”)、SdrH样多肽(“2”)、Lip2(“3”)、推定的蛋白质(“4”)、Atl(“5”)和假设蛋白质(“6”)。灰色：Nuc(“G”)、LukG(“I”)和SdrH样多肽(“2”)。

如图所示，在至少两种不同的条件下，只有五种多肽与摄取的显著增加有关：Nuc(“G”)、Hla(“H”)、LukG(“I”)、IsdA(“K”)和SdrH样多肽(“2”)；请注意，对于1/1000和1/2000的稀释度观察到的值是相似的，指示缺乏阈值效应。

图2.对金黄色葡萄球菌的杀死

金黄色葡萄球菌的杀死(感染后6h)，感染复数(MOI)为10：1(左图)和25：1(右图)，使用1/1000(上图)和1/2000(下图)稀释的免疫血清。报告的蛋白质在6h时间点的平均荧光面积(激发488nm，发射515nm)在此相对于相同蛋白质在3h时间点测量的值(参考值1)进行归一化。测试的蛋白质与以上列出的那些相同(参见图1的图例)。灰色：Nuc(“G”)、LukG(“I”)和SdrH样多肽(“2”)。

如图所示，在所有测定的条件中，在与对金黄色葡萄球菌的摄取显著增加相关的五种抗原中只有三种也与杀死细菌相关：Nuc(“G”)、LukG(“I”)和SdrH样多肽(“2”)。

图3.用抗IsdB蛋白质和抗SdrH样蛋白质的抗血清处理的金黄色葡萄球菌感染的巨噬细胞，在感染后6小时的照片(MOI 1：10，血清稀释度1/1000)。

使用抗IsdB(“M”)蛋白质的抗血清(图A)，可以看到无数细菌(白色圆圈)充满细胞质空间；还可以观察到细胞裂解区域和释放出细胞外细菌。这与使用抗SdrH样多肽(“2”)的抗血清(图B)获得的图片形成对比：可以计数单个细菌(白色圆圈)；细胞骨架结构得以保留以及细胞核区域得以保留。用抗-Nuc(“G”)蛋白质和抗-LukG(“I”)蛋白质的抗血清进行得到相似的观察结果(数据未显示)。

实施例

纳入以下实施例以阐明本发明优选的实施方案。在以下实施例和附图中列出或所示的所有主题，用于阐释说明，而非限制意义。以下实施例包括可以由本领域技术人员确定的任何替代、等同和修改。

实施例1：金黄色葡萄球菌和对照抗原的构建、生产和纯化

材料和方法

将编码本发明的金黄色葡萄球菌抗原和金黄色葡萄球菌对照抗原的基因克隆至 表达载体中

测序的金黄色葡萄球菌菌株Mu50用作基因组DNA的来源。使用商业试剂盒(DNeasyBlood and Tissue，Qiagen Hilden，德国)进行DNA提取。使用AmplifX设计的合适引物，通过聚合酶链式反应(PCR)扩增感兴趣的金黄色葡萄球菌基因。

金黄色葡萄球菌基因的核苷酸序列尤其如SEQ ID NO：1、5、9、13、17、21、25、29、33、37、41、45、49、53、57、61、65、69、73和79中所提供。克隆的DNA序列如SEQ ID NO：2、6、10、14、18、22、26、30、34、38、42、46、50、54、58、62、66、70、74、75、80和81中所提供的。特别地，针对sdrD和clfA基因克隆了两种不同的多肽(对于sdrD是SEQ ID NO：74和75，对于clfA为SEQID NO：80和81)。在用SalI和StuI(Thermo Scientific，Waltham，USA)限制性酶切之前，纯化DNA以及含有多组氨酸标签的表达载体pET-6xHN-N(Clontech，Otsu，日本)。然后，将限制性消化的PCR产物连接到载体中。通过电泳迁移控制所得到的每个基因的表达载体，然后将所述表达载体转化至化学感受态的DH10β1大肠杆菌(Thermo Scientific)中。将转化的细菌在Luria-Bertani(LB)肉汤中在35℃中孵育1h，然后铺板在含有氨苄青霉素(100mg/L)的LB琼脂上，并在35℃孵育过夜。收获分离的菌落，在LB肉汤中生长过夜以扩增克隆。然后使用商业试剂盒(QIAprep Spin Miniprep，Qiagen)纯化载体DNA。进行测序以验证每个插入的基因序列。pET-6xHN-GFPuv载体(Clontech)用于表达绿色荧光蛋白(GFP，克隆的DNA和氨基酸序列分别为SEQ ID NO：85和86)。

抗原生产和纯化

使用经过验证的载体，按照与DH10β1细胞相同的操作方案转化化学感受态的BL21(DE3)大肠杆菌细胞(Thermo Scientific)，对分离出的菌落进行类似的扩增。将过夜培养物的1/100稀释液在35℃下孵育，直到培养物达到0.5的光密度(OD)。然后，将IPTG溶液(1mM终浓度)添加到细菌中，以在35℃下诱导抗原产生，直到OD达到1.2。对通过离心获得的细菌沉淀进行裂解，并使用商业试剂盒(Proteus Metal Chelate，Generon，Slough，UK)纯化带组氨酸标签的蛋白质，使用10mM的咪唑溶液洗脱重组的带组氨酸标签的蛋白质。然后，使用Amicon Ultra–15柱(Merck，Darmstadt，德国)浓缩洗脱的抗原。所述抗原的多肽序列如在SEQ ID NO：3、7、11、15、19、23、27、31、35、39、43、47、51、55、59、63、67、71、76和82中所提供。全部所克隆的多肽序列进一步包含N-末端组氨酸标签，在SEQ ID NO：4、8、12、16、20、24、28、32、36、10、44、48、52、56、60、64、68、72、77、78、83和84中提供。

抗原表征

通过用考马斯溶液染色的十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)对纯化的抗原进行表征，以评估重组抗原的大小、完整性和纯度。使用Bradford法确定纯化抗原溶液的浓度。

结果

克隆、表达和纯化了(纯度>95％)作为22种不同多肽评价的共计20种金黄色葡萄球菌的抗原，对于每种重组蛋白质而言，纯化蛋白质总量为1mg至6mg。

这些蛋白质中的四种包含在正在进行药物开发的抗金黄色葡萄球菌的疫苗中，用作对照疫苗抗原：IsdB(描述在Harro等人，2010，Moustafa等人，2012，Fowler等人，2013)、MntC(描述在Salazar等人，2014，Begier等人，2017，Inoue等人，2018)、ClfA(描述在Salazar等人，2014，Begier等人，2017，Inoue等人，2018)和Hlaα毒素(描述在Landrum等人，2016)。

实施例2：产生针对金黄色葡萄球菌抗原的抗体

材料和方法

通过对无特定病原体的BALB/cJRj小鼠(特别记录到来源于无金黄色葡萄球菌的环境)进行免疫接种，获得靶向金黄色葡萄球菌多肽和对照抗原的抗体。小鼠在九周龄时接收，在免疫前一周适应环境。对于每种抗原为每组六只小鼠注射第一剂20μg的纯化抗原和弗氏完全佐剂，然后在第21天和第42天再注射两次20μg的抗原和弗氏不完全佐剂。在第一次注射后的第50天，处死小鼠并收集血清。对第一个对照组(n＝6)使用GFP(不相关的非金黄色葡萄球菌抗原)注射。将第二个对照组(n＝6)注射磷酸盐缓冲液(PBS)作为佐剂免疫原性的对照。

通过蛋白质印迹使用纯化的蛋白质验证每种免疫血清的滴度和特异性。

结果

将每种血清连续稀释降至60,000滴度对其进行评价。所有测试的血清样品在该浓度下均显示出阳性特异性条带，表明所有动物均得到有效免疫接种。将用相同抗原免疫的六只小鼠的血清合并在一起，以获得针对22种金黄色葡萄球菌多肽的每一种和GFP的单一免疫血清原液。

实施例3：在基于巨噬细胞的OPA测定中对于免疫血清的体外评价

材料和方法

金黄色葡萄球菌菌株

用USA300及其spA^-衍生物(Frédéric Laurent，Lyon)进行实验。

巨噬细胞培养

对小鼠BALB/c的永生化的巨噬细胞系J774.2(欧洲细胞培养物保藏中心，PortonDown，UK)进行细胞测定。巨噬细胞在35℃和5％CO₂气氛下培养在补充有10％胎牛血清的Dulbecco改良的Eagle培养基(DMEM)中。在测定前24h，将细胞悬浮在补充的DMEM(complemented DMEM)中，滴定，然后接种在培养平板中。

基于巨噬细胞的测定法

将在脑心浸液(BHI)肉汤中的培养18h的金黄色葡萄球菌培养物在新鲜培养基中以1/100进行稀释，在37℃下孵育直到培养物的OD达到1。加入以1/1000或1/2000稀释的免疫血清，并允许在35℃下1h以结合至细菌表面。然后以10：1(每个细胞10个细菌)和25：1(每个细胞25个细菌)的感染复数(MOI)，将血清处理的细菌添加到滴定的J774.2细胞单层中。在35℃和5％CO₂气氛下孵育1h后，将孔中的培养基清空，用PBS轻轻洗涤，然后加入含有庆大霉素的新鲜DMEM。在合适的时间(见下文：对于细菌摄取为感染后3h；对于细菌杀死为感染后6h)，用PBS洗涤J774.2细胞，用4％的PFA固定5分钟，然后用0.1％Triton×100渗透5分钟。固定后的细胞用赫斯特染料(Hoechst)33342(Thermo Scientific)、Phalloidin-ATTO655(Sigma-Aldrich，Saint-Louis，USA)和

FL万古霉素(VMB)(Invitrogen，Carlsbad，USA)染色30分钟，然后使用玻璃盖玻片进行密封。使用Leica SP8共聚焦显微镜获取图像，使用ImageJ软件(国立卫生研究院，Bethesda，USA)进行分析。

评价对细菌的摄取和杀死

通过将每个抗原特异性血清对应的每个J774.2细胞的具有VMB荧光的像素的数目(细菌细胞壁定量)与不相关的对照血清(抗GFP)对应的每个J774.2细胞的具有VMB荧光的像素的数目进行比较，评价在感染后3h对血清处理的细菌的摄取。

为评价内化细菌的结果，将感染后3h和感染后6h的VMB面积进行比较。当测量到荧光增加时称为细菌生长，这反映了细胞内的肽聚糖量增加。当测量到细胞内的肽聚糖量减少时，称为细菌溶解(“杀死”)，这反映了细胞内的肽聚糖量的减少。

结果

此处显示：两种抗体稀释液(1：1000、1：2000)与金黄色葡萄球菌一起孵育后，以10：1和25：1的MOI感染，在感染后3小时评价对细菌的摄取，特征在于在每个实验中的抗GFP对照血清用于归一化。至少在两个条件下，五种抗原表现出明显不同的行为，其中对金黄色葡萄球菌的内化显著增加：蛋白质SdrH样多肽(“2”)、Nuc(“G”)和LukG(“I”)、Hla(“H”)和IsdA(“K”)(图1)。

通过比较感染后6小时的VMB荧光面积与感染后3小时观察到的荧光面积，对于在细胞内的细菌清除和生长进行评价。在之前证明的与显著的对细菌摄取相关的五种抗原中，三种抗原在所有实验条件下与对细菌的杀死有关：SdrH样多肽(“2”)、Nuc(“G”)和LukG(“I”)(图2)。

值得注意的是，许多对摄取没有显著影响的蛋白质与细菌生长增强有关(免疫血清的“促进”作用)(参见，例如图2中的蛋白质Pbp2a(“A”)和Sak(“C”)，其中MOI为25：1，血清稀释度为1/1000)。使用抗IsdB蛋白血清时，细菌生长特别强烈，导致破坏了巨噬细胞单层(图3)，使得细胞内细菌的负载被低估(将图1&图2与图3进行比较)。

实施例4：建立小鼠的全身性金黄色葡萄球菌感染的体内模型

之前的研究表明，BALB/c小鼠对血液中传播的金黄色葡萄球菌感染是高度易感的，因为这种小鼠品系无法抑制肾脏中细菌生长(von

-Blickwede等人，2008)。然而，由于金黄色葡萄球菌菌株的感染过程可能根据其毒力库(virulence repertoire)而有所不同，我们首先确定金黄色葡萄球菌USA300的哪个剂量会导致非致死性的肾脏感染。

材料和方法

金黄色葡萄球菌菌株

用金黄色葡萄球菌菌株USA300进行实验。

小鼠

雌性BALB/c小鼠购自Janvier Labs(Le Genest Saint Isle，法国)。小鼠在六周龄时被接收，并在免疫前一周适应环境。根据机构和国家伦理准则(协议APAFIS#26827)进行动物实验。

全身性的金黄色葡萄球菌感染的小鼠模型

通过腹腔内施用氯胺酮/甲苯噻嗪(50/10mg/kg)对小鼠进行麻醉，通过眶后窦注射接种100μL体积中的10⁹、10⁷或10⁵CFU的USA300。在感染后3小时和24小时，对小鼠实施安乐死。采集脾脏和肾脏，均质化，并将连续稀释液铺板在Mueller Hinton 2的琼脂板上。在37℃孵育24小时后，计数CFU(最小检出限：每个器官2.69log₁₀CFU)。

结果

在攻击后24h时间点之前，10⁹CFU的剂量导致100％的动物死亡，但是10⁵CFU无法在肾脏中建立感染(攻击后3h和24h未检测到细菌)(表2)。

因此，10⁷CFU是唯一不致死且与肾脏感染相关的剂量。正如预期的那样，在攻击后3h和24h，脾脏中的细菌负荷相似，表明感染得到控制，而肾脏中细菌生长则显著增加(在攻击后3h和24h之间的CFU差异为ca 4 log₁₀)(表2)。

表2.在未免疫的动物中，在攻击后3h和24h的CFU计数。

^a对于每个器官以及每个时间点的四个动物的组。

^b在攻击后24h时间点之前，所有动物都死亡。

^c检测不到(最小检出限，2.69log₁₀CFU)。

实施例5：在全身性的金黄色葡萄球菌感染的小鼠模型中评价SdrH样多肽相比于阴性对照的保护作用

BALB/c小鼠已被证明能够通过产生强烈的Th2反应来控制金黄色葡萄球菌感染(Nippe等，2011)。我们之前在OPA测定法中表明，针对SdrH样多肽、Nuc或LukG的血清增强吞噬细胞对金黄色葡萄球菌的杀死(参见实施例3)。因此，我们研究了使用这三种抗原之一的SdrH样多肽(“SdrH样”)对BALB/c小鼠进行疫苗接种，是否允许在这种全身感染的模型中改善对肾脏感染的控制。

材料和方法

SdrH样、佐剂的产生和纯化

如实施例1所述产生和纯化SdrH样。根据制造商的建议使用佐剂(氢氧化铝凝胶

和磷酸铝凝胶(Adju-

)；InVivoGen，CA，USA)。

疫苗接种操作方案和终点分析

用10μg的纯化的SdrH样(5μg与氢氧化铝凝胶(右大腿；体积：50μL)以及5μg与磷酸铝凝胶(左大腿，体积：50μL))对小鼠进行肌肉内免疫，一周一次，共三周；仅接受相同量佐剂的小鼠用作阴性对照。

在第三次免疫后的两周，向小鼠(每个时间点六只小鼠的组)免疫接种10⁷CFU剂量的USA300；该操作方案在其他方面如实施例4中所述。

结果

如表3所示，用SdrH样进行疫苗接种的小鼠相较于对照小鼠，在攻击后24h的细菌负载减少了0.53log₁₀CFU。虽然在疫苗接种的小鼠中肾脏感染没有得到控制，但细菌生长显著减少(在攻击后3h至24h之间为+1.53log₁₀CFU，与之相比的对照小鼠为+2.06log10 CFU)。

正如预期的那样，疫苗接种对脾脏感染影响很小。

表3.使用SdrH样与阴性对照免疫的动物在攻击后3h和24h的CFU计数。

^a对于每个器官以及在每个时间点的六个动物的组。

^b仅有佐剂。

实施例6：在全身性金黄色葡萄球菌感染的小鼠模型中评价SdrH样相对葡萄球菌激酶和MntC的保护性作用

然后，将SdrH样与葡萄球菌激酶和MntC进行比较。选择第一个比较物葡萄球菌激酶，是因为在OPA测定法中，针对该蛋白质的血清反常地显示出有利于金黄色葡萄球菌在细胞内生长(参见在图1和图2中的Sak(“C”))。选择第二个比较物MntC，是因为MntC已在各种动物模型中被证明是有希望的候选疫苗(Anderson等人，2012)，而在OPA测定法中MntC被发现不如SdrH样(参见在图1和图2中的MntC(“1”))。

测试了三种感染剂量：10⁷、3×10⁶和10⁶CFU。

材料和方法

如实施例1所述，产生和纯化SdrH样、葡萄球菌激酶和MntC。疫苗接种操作方案和终点分析如实施例5中所述，不同之处在于使用三种剂量评价保护性效作用：10⁷CFU、3×10⁶CFU和10⁶CFU的USA300。

结果

与用葡萄球菌激酶进行疫苗接种的小鼠相比，用SdrH样进行疫苗接种的小鼠的肾脏感染过程明显不同(表4)；无论USA300的剂量如何，与葡萄球菌激酶相比，SdrH样将肾脏中的细菌负载减少了ca 0.80log₁₀CFU(表5)。

在最低剂量时(即10⁶CFU)，与葡萄球菌激酶相比，使用MntC观察到类似的CFU减少(0.95log₁₀CFU)(表5)；然而在10⁷和3×10⁶CFU时差异要小得多(仅减少0.30至0.39log₁₀CFU；表5)。

与上述结果一致，在两个最高剂量,即10⁷和3×10⁶CFU时，SdrH样对肾脏感染的作用似乎比MntC更强(分别减少0.45和0.47log₁₀CFU；表5)，而在10⁶CFU时，发现相似的结果。

因此，用SdrH样、葡萄球菌激酶和MntC进行疫苗接种后，在肾脏中观察到的细菌动力学与在OPA测定法中用这三种抗原观察到的细菌动力学平行。

正如预期的那样，用这三种抗原中的每一种进行疫苗接种对脾脏感染的影响很小。

表4.使用SdrH样与葡萄球菌激酶和MntC免疫的动物在攻击后3h和24h的CFU计数。

^a对于每个器官以及在每个时间点的六个动物的组。

^b在3h至24h之间的细菌生长用“+”表示，细菌杀死用“-”表示。

表5.在肾脏中3h-24h的CFU差异的成对比较。

^a粗体，差异≥0.5log₁₀CFU。

结论

特异性抗体与金黄色葡萄球菌的结合可能对宿主有益，因为这种结合可以抑制细胞外抗原的生理功能，增加被免疫细胞摄取，促进吞噬作用和/或增加将细菌靶向至吞噬溶酶体区室。更特别地，针对金黄色葡萄球菌抗原的抗体可以抑制将细菌靶向有利的细胞内微环境的细菌防御机制，通过增加用于抗原提呈的细菌的加工以提高免疫反应，促进对细菌的清除。然而，某些抗体具有有害作用，通过抑制免疫系统充分识别的并参与宿主对感染控制的决定簇的功能，增强了细菌的毒力。候选疫苗产生的体液反应应优选地增加摄取细菌，从而实现最佳的抗原提呈以及增强细胞内的细菌裂解。

出人意料地是，针对SdrH样多肽、Nuc或LukG的血清显示既促进巨噬细胞对金黄色葡萄球菌的内化，又增强吞噬作用后对金黄色葡萄球菌的细胞内清除。

值得注意的是，之前开发的并在临床试验中显示是无效的针对候选疫苗蛋白质Hla、MntC和ClfA的抗血清中没有一种组合了此处报告的两种特性。此外，在此处报告的巨噬细胞测定法中，IsdB候选疫苗(其显示出使接种疫苗患者的结果恶化)被证明是有害的，在增强内化后急剧破坏了巨噬细胞层。这些结果进一步证实，本文提供的新的基于巨噬细胞的体外测定法在鉴定赋予受试者对金黄色葡萄球菌引起的疾病的保护作用的抗原上的针对性。

此外，使用BALB/c小鼠在金黄色葡萄球菌感染的全身模型中体内证实了基于巨噬细胞的体外测定法的结果，所述BALB/c小鼠由于无法限制肾脏中的细菌生长而对金黄色葡萄球菌高度易感。实际上，在该模型中评价的三种抗原中，SdrH样多肽对肾脏中总体金黄色葡萄球菌的细菌生长显示出最强的抑制作用，其次是MntC，这与在巨噬细胞测定法中观察到的动力学一致。

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序列表

<110> 安踏格尼斯公司

凡尔赛大学

法国公立援助医院

<120> 用于预防金黄色葡萄球菌感染的组合物和方法

<130> D39006

<150> EP19306797.2

<151> 2019-12-31

<160> 86

<170> PatentIn version 3.5

<210> 1

<211> 687

<212> DNA

<213> 金黄色葡萄球菌

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atgacagaat acttattaag tgctggcata tgtatggcaa ttgtttcaat attacttata 60

gggatggcta tcagtaatgt ttcgaaaggg caatacgcaa agaggttttt ctttttcgct 120

actagttgct tagtgttaac tttagttgta gtttcaagtc taagtagctc agcaaatgca 180

tcacaaacag ataacggcgt aaatagaagt ggttctgaag atccaacagt atatagtgca 240

acttcaacta aaaaattaca taaagaacct gcgacattaa ttaaagcgat tgatggtgat 300

acggttaaat taatgtacaa aggtcaacca atgacattca gactattatt agttgataca 360

cctgaaacaa agcatcctaa aaaaggtgta gagaaatatg gccctgaagc aagtgcattt 420

acgaaaaaaa tggtagaaaa tgcaaataaa attgaagtcg agtttgacaa aggtcaaaga 480

actgataaat atggacgtgg cttagcgtat atttatgctg atggaaaaat ggtaaacgaa 540

gctttagttc gtcaaggctt ggctaaagtt gcttatgttt ataaacctaa caatacacat 600

gaacaacttt taagaaaaag tgaagcacaa gcgaaaaaag agaaattaaa tatttggagc 660

gaagacaacg ctgattcagg tcaataa 687

<210> 2

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aatgtttcga aagggcaata cgcaaagagg tttttctttt tcgctactag ttgcttagtg 60

ttaactttag ttgtagtttc aagtctaagt agctcagcaa atgcatcaca aacagataac 120

ggcgtaaata gaagtggttc tgaagatcca acagtatata gtgcaacttc aactaaaaaa 180

ttacataaag aacctgcgac attaattaaa gcgattgatg gtgatacggt taaattaatg 240

tacaaaggtc aaccaatgac attcagacta ttattagttg atacacctga aacaaagcat 300

cctaaaaaag gtgtagagaa atatggccct gaagcaagtg catttacgaa aaaaatggta 360

gaaaatgcaa ataaaattga agtcgagttt gacaaaggtc aaagaactga taaatatgga 420

cgtggcttag cgtatattta tgctgatgga aaaatggtaa acgaagcttt agttcgtcaa 480

ggcttggcta aagttgctta tgtttataaa cctaacaata cacatgaaca acttttaaga 540

aaaagtgaag cacaagcgaa aaaagagaaa ttaaatattt ggagcgaaga caacgctgat 600

tcaggtcaat aa 612

<210> 3

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Val Val Val Ser Ser Leu Ser Ser Ser Ala Asn Ala Ser Gln Thr Asp

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Asn Gly Val Asn Arg Ser Gly Ser Glu Asp Pro Thr Val Tyr Ser Ala

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Thr Ser Thr Lys Lys Leu His Lys Glu Pro Ala Thr Leu Ile Lys Ala

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Ile Asp Gly Asp Thr Val Lys Leu Met Tyr Lys Gly Gln Pro Met Thr

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Phe Arg Leu Leu Leu Val Asp Thr Pro Glu Thr Lys His Pro Lys Lys

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Gly Val Glu Lys Tyr Gly Pro Glu Ala Ser Ala Phe Thr Lys Lys Met

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Val Glu Asn Ala Asn Lys Ile Glu Val Glu Phe Asp Lys Gly Gln Arg

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Thr Asp Lys Tyr Gly Arg Gly Leu Ala Tyr Ile Tyr Ala Asp Gly Lys

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Val Tyr Lys Pro Asn Asn Thr His Glu Gln Leu Leu Arg Lys Ser Glu

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Ala Gln Ala Lys Lys Glu Lys Leu Asn Ile Trp Ser Glu Asp Asn Ala

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Asp Ser Gly Gln

225

<210> 4

<211> 203

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Asn Val Ser Lys Gly Gln Tyr Ala Lys Arg Phe Phe Phe Phe Ala Thr

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Ser Cys Leu Val Leu Thr Leu Val Val Val Ser Ser Leu Ser Ser Ser

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Ala Asn Ala Ser Gln Thr Asp Asn Gly Val Asn Arg Ser Gly Ser Glu

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Asp Pro Thr Val Tyr Ser Ala Thr Ser Thr Lys Lys Leu His Lys Glu

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Pro Ala Thr Leu Ile Lys Ala Ile Asp Gly Asp Thr Val Lys Leu Met

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Tyr Lys Gly Gln Pro Met Thr Phe Arg Leu Leu Leu Val Asp Thr Pro

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Glu Thr Lys His Pro Lys Lys Gly Val Glu Lys Tyr Gly Pro Glu Ala

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Ser Ala Phe Thr Lys Lys Met Val Glu Asn Ala Asn Lys Ile Glu Val

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Glu Phe Asp Lys Gly Gln Arg Thr Asp Lys Tyr Gly Arg Gly Leu Ala

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Tyr Ile Tyr Ala Asp Gly Lys Met Val Asn Glu Ala Leu Val Arg Gln

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Gly Leu Ala Lys Val Ala Tyr Val Tyr Lys Pro Asn Asn Thr His Glu

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Gln Leu Leu Arg Lys Ser Glu Ala Gln Ala Lys Lys Glu Lys Leu Asn

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Ile Trp Ser Glu Asp Asn Ala Asp Ser Gly Gln Asn Val Ser Lys Gly

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Gln Tyr Ala Lys Arg Phe Phe Phe Phe Ala Thr Ser Cys Leu Val Leu

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Thr Leu Val Val Val Ser Ser Leu Ser Ser Ser Ala Asn Ala Ser Gln

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Thr Asp Asn Gly Val Asn Arg Ser Gly Ser Glu Asp Pro Thr Val Tyr

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Ser Ala Thr Ser Thr Lys Lys Leu His Lys Glu Pro Ala Thr Leu Ile

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Lys Ala Ile Asp Gly Asp Thr Val Lys Leu Met Tyr Lys Gly Gln Pro

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Met Thr Phe Arg Leu Leu Leu Val Asp Thr Pro Glu Thr Lys His Pro

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Lys Lys Gly Val Glu Lys Tyr Gly Pro Glu Ala Ser Ala Phe Thr Lys

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Lys Met Val Glu Asn Ala Asn Lys Ile Glu Val Glu Phe Asp Lys Gly

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Gln Arg Thr Asp Lys Tyr Gly Arg Gly Leu Ala Tyr Ile Tyr Ala Asp

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Gly Lys Met Val Asn Glu Ala Leu Val Arg Gln Gly Leu Ala Lys Val

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Ala Tyr Val Tyr Lys Pro Asn Asn Thr His Glu Gln Leu Leu Arg Lys

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Ser Glu Ala Gln Ala Lys Lys Glu Lys Leu Asn Ile Trp Ser Glu Asp

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Asn Ala Asp Ser Gly Gln

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<210> 5

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atgtcatatc attggtttaa gaaaatgtta ctttcaacaa gtattttaat tttaagtagt 60

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ccaactacta atttgaatca taatataact tcaccatcag taaatagtga aatgaataat 180

aatgagactg ggacacctca cgaatcaaat caaacgggta atgaaggaac aggttcgaat 240

agtcgtgatg ctaatcctga ttcgaataat gtgaagccag actcaaacaa ccaaaaccca 300

agtacagatt caaaaccaga cccaaataac caaaacccaa gtccgaatcc aaaaccagat 360

ccagataacc cgaaaccaaa accagaccca gataaaccaa agccaaatct ggatccaaaa 420

ccagatccag ataacccgaa accaaaacca gatccaaaac cagacccaga taaaccaaag 480

ccaaatccgg atccaaaacc agatccagat aaaccaaagc caaatccgaa tccaaaacca 540

gaccctaata agccaaatcc taacccgtca ccagatcccg atcaacctgg ggattcaaat 600

cattctggtg gctcgaaaaa tgggggaaca tggaacccaa atgcttcaga tggatctaat 660

caaggtcaat ggcaaccaaa tgggaatcaa ggaaactcac aaaatcctac tggtaatgat 720

tttgtatccc aacgattttt agccttggca aatggggctt acaagtataa tccgtatatt 780

ttaaatcaaa ttaataagtt gggcaaagat tatggagaag ttactgatga agacatttat 840

aatattattc gaaaacaaaa tttcagcgga aatgcatatt taaatggatt acaacagcaa 900

tcgaattact ttagattcca atatttcaat ccattgaaat cagaaaggta ctatcgtaat 960

ttagatgaac aagtactcgc attaattact ggtgaaattg gatcaatgcc agatttgaaa 1020

aagcccgaag ataagccgga ttcaaaacaa cgctcatttg aaccgcatga aaaagacgat 1080

tttacagtag ttaaaaaaca agaagataat aagaaaagtg cgtcaactgc atatagtaaa 1140

agttggctag caattgtatg ttctatgatg gtggtatttt caatcatgct attcttattt 1200

gtaaagcgaa ataaaaagaa aaataaaaac gaatcacagc gacgataa 1248

<210> 6

<211> 1149

<212> DNA

<213> 人工序列

<220>

<223> SdrH样 -克隆的DNA序列

<400> 6

gataacttaa atggagaaaa accaactact aatttgaatc ataatataac ttcaccatca 60

gtaaatagtg aaatgaataa taatgagact gggacacctc acgaatcaaa tcaaacgggt 120

aatgaaggaa caggttcgaa tagtcgtgat gctaatcctg attcgaataa tgtgaagcca 180

gactcaaaca accaaaaccc aagtacagat tcaaaaccag acccaaataa ccaaaaccca 240

agtccgaatc caaaaccaga tccagataac ccgaaaccaa aaccagaccc agataaacca 300

aagccaaatc tggatccaaa accagatcca gataacccga aaccaaaacc agatccaaaa 360

ccagacccag ataaaccaaa gccaaatccg gatccaaaac cagatccaga taaaccaaag 420

ccaaatccga atccaaaacc agaccctaat aagccaaatc ctaacccgtc accagatccc 480

gatcaacctg gggattcaaa tcattctggt ggctcgaaaa atgggggaac atggaaccca 540

aatgcttcag atggatctaa tcaaggtcaa tggcaaccaa atgggaatca aggaaactca 600

caaaatccta ctggtaatga ttttgtatcc caacgatttt tagccttggc aaatggggct 660

tacaagtata atccgtatat tttaaatcaa attaataagt tgggcaaaga ttatggagaa 720

gttactgatg aagacattta taatattatt cgaaaacaaa atttcagcgg aaatgcatat 780

ttaaatggat tacaacagca atcgaattac tttagattcc aatatttcaa tccattgaaa 840

tcagaaaggt actatcgtaa tttagatgaa caagtactcg cattaattac tggtgaaatt 900

ggatcaatgc cagatttgaa aaagcccgaa gataagccgg attcaaaaca acgctcattt 960

gaaccgcatg aaaaagacga ttttacagta gttaaaaaac aagaagataa taagaaaagt 1020

gcgtcaactg catatagtaa aagttggcta gcaattgtat gttctatgat ggtggtattt 1080

tcaatcatgc tattcttatt tgtaaagcga aataaaaaga aaaataaaaa cgaatcacag 1140

cgacgataa 1149

<210> 7

<211> 415

<212> PRT

<213> 金黄色葡萄球菌

<400> 7

Met Ser Tyr His Trp Phe Lys Lys Met Leu Leu Ser Thr Ser Ile Leu

1 5 10 15

Ile Leu Ser Ser Ser Ser Leu Gly Leu Ala Thr His Thr Val Glu Ala

20 25 30

Lys Asp Asn Leu Asn Gly Glu Lys Pro Thr Thr Asn Leu Asn His Asn

35 40 45

Ile Thr Ser Pro Ser Val Asn Ser Glu Met Asn Asn Asn Glu Thr Gly

50 55 60

Thr Pro His Glu Ser Asn Gln Thr Gly Asn Glu Gly Thr Gly Ser Asn

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Ser Arg Asp Ala Asn Pro Asp Ser Asn Asn Val Lys Pro Asp Ser Asn

85 90 95

Asn Gln Asn Pro Ser Thr Asp Ser Lys Pro Asp Pro Asn Asn Gln Asn

100 105 110

Pro Ser Pro Asn Pro Lys Pro Asp Pro Asp Asn Pro Lys Pro Lys Pro

115 120 125

Asp Pro Asp Lys Pro Lys Pro Asn Leu Asp Pro Lys Pro Asp Pro Asp

130 135 140

Asn Pro Lys Pro Lys Pro Asp Pro Lys Pro Asp Pro Asp Lys Pro Lys

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Pro Asn Pro Asp Pro Lys Pro Asp Pro Asp Lys Pro Lys Pro Asn Pro

165 170 175

Asn Pro Lys Pro Asp Pro Asn Lys Pro Asn Pro Asn Pro Ser Pro Asp

180 185 190

Pro Asp Gln Pro Gly Asp Ser Asn His Ser Gly Gly Ser Lys Asn Gly

195 200 205

Gly Thr Trp Asn Pro Asn Ala Ser Asp Gly Ser Asn Gln Gly Gln Trp

210 215 220

Gln Pro Asn Gly Asn Gln Gly Asn Ser Gln Asn Pro Thr Gly Asn Asp

225 230 235 240

Phe Val Ser Gln Arg Phe Leu Ala Leu Ala Asn Gly Ala Tyr Lys Tyr

245 250 255

Asn Pro Tyr Ile Leu Asn Gln Ile Asn Lys Leu Gly Lys Asp Tyr Gly

260 265 270

Glu Val Thr Asp Glu Asp Ile Tyr Asn Ile Ile Arg Lys Gln Asn Phe

275 280 285

Ser Gly Asn Ala Tyr Leu Asn Gly Leu Gln Gln Gln Ser Asn Tyr Phe

290 295 300

Arg Phe Gln Tyr Phe Asn Pro Leu Lys Ser Glu Arg Tyr Tyr Arg Asn

305 310 315 320

Leu Asp Glu Gln Val Leu Ala Leu Ile Thr Gly Glu Ile Gly Ser Met

325 330 335

Pro Asp Leu Lys Lys Pro Glu Asp Lys Pro Asp Ser Lys Gln Arg Ser

340 345 350

Phe Glu Pro His Glu Lys Asp Asp Phe Thr Val Val Lys Lys Gln Glu

355 360 365

Asp Asn Lys Lys Ser Ala Ser Thr Ala Tyr Ser Lys Ser Trp Leu Ala

370 375 380

Ile Val Cys Ser Met Met Val Val Phe Ser Ile Met Leu Phe Leu Phe

385 390 395 400

Val Lys Arg Asn Lys Lys Lys Asn Lys Asn Glu Ser Gln Arg Arg

405 410 415

<210> 8

<211> 382

<212> PRT

<213> 人工序列

<220>

<223> SdrH样 -克隆的肽序列

<400> 8

Asp Asn Leu Asn Gly Glu Lys Pro Thr Thr Asn Leu Asn His Asn Ile

1 5 10 15

Thr Ser Pro Ser Val Asn Ser Glu Met Asn Asn Asn Glu Thr Gly Thr

20 25 30

Pro His Glu Ser Asn Gln Thr Gly Asn Glu Gly Thr Gly Ser Asn Ser

35 40 45

Arg Asp Ala Asn Pro Asp Ser Asn Asn Val Lys Pro Asp Ser Asn Asn

50 55 60

Gln Asn Pro Ser Thr Asp Ser Lys Pro Asp Pro Asn Asn Gln Asn Pro

65 70 75 80

Ser Pro Asn Pro Lys Pro Asp Pro Asp Asn Pro Lys Pro Lys Pro Asp

85 90 95

Pro Asp Lys Pro Lys Pro Asn Leu Asp Pro Lys Pro Asp Pro Asp Asn

100 105 110

Pro Lys Pro Lys Pro Asp Pro Lys Pro Asp Pro Asp Lys Pro Lys Pro

115 120 125

Asn Pro Asp Pro Lys Pro Asp Pro Asp Lys Pro Lys Pro Asn Pro Asn

130 135 140

Pro Lys Pro Asp Pro Asn Lys Pro Asn Pro Asn Pro Ser Pro Asp Pro

145 150 155 160

Asp Gln Pro Gly Asp Ser Asn His Ser Gly Gly Ser Lys Asn Gly Gly

165 170 175

Thr Trp Asn Pro Asn Ala Ser Asp Gly Ser Asn Gln Gly Gln Trp Gln

180 185 190

Pro Asn Gly Asn Gln Gly Asn Ser Gln Asn Pro Thr Gly Asn Asp Phe

195 200 205

Val Ser Gln Arg Phe Leu Ala Leu Ala Asn Gly Ala Tyr Lys Tyr Asn

210 215 220

Pro Tyr Ile Leu Asn Gln Ile Asn Lys Leu Gly Lys Asp Tyr Gly Glu

225 230 235 240

Val Thr Asp Glu Asp Ile Tyr Asn Ile Ile Arg Lys Gln Asn Phe Ser

245 250 255

Gly Asn Ala Tyr Leu Asn Gly Leu Gln Gln Gln Ser Asn Tyr Phe Arg

260 265 270

Phe Gln Tyr Phe Asn Pro Leu Lys Ser Glu Arg Tyr Tyr Arg Asn Leu

275 280 285

Asp Glu Gln Val Leu Ala Leu Ile Thr Gly Glu Ile Gly Ser Met Pro

290 295 300

Asp Leu Lys Lys Pro Glu Asp Lys Pro Asp Ser Lys Gln Arg Ser Phe

305 310 315 320

Glu Pro His Glu Lys Asp Asp Phe Thr Val Val Lys Lys Gln Glu Asp

325 330 335

Asn Lys Lys Ser Ala Ser Thr Ala Tyr Ser Lys Ser Trp Leu Ala Ile

340 345 350

Val Cys Ser Met Met Val Val Phe Ser Ile Met Leu Phe Leu Phe Val

355 360 365

Lys Arg Asn Lys Lys Lys Asn Lys Asn Glu Ser Gln Arg Arg

370 375 380

<210> 9

<211> 1056

<212> DNA

<213> 金黄色葡萄球菌

<400> 9

atgaaaaata aaaaacgtgt tttaatagcg tcatcattat catgtgcaat tttattgtta 60

tcagcagcaa cgactcaagc aaattcagct cataaagact cgcaagatca aaataagaaa 120

gaacatgttg ataagtctca acaaaaagac aaacgtaatg ttactaataa agataaaaat 180

tcaacagtac ctgatgatat tgggaaaaac ggtaaaatca caaaacgaac tgaaacagta 240

tatgatgaga aaacaaatat actccaaaat ttacaattcg actttatcga tgatccaact 300

tatgacaaga atgtattact tgttaaaaaa caaggctcaa ttcattcaaa tttaaagttt 360

gaatctcata aagaagaaaa aaattcaaat tggttaaagt atccaagtga gtaccatgta 420

gattttcaag taaaaagaaa tcgtaaaact gaaatattag accaattgcc gaaaaataaa 480

atttcaactg cgaaagtaga cagtacattt tcatatagct caggtggtaa attcgattca 540

acgaaaggta ttggacgaac ttcatcaaat agctactcca aaacgattag ttataatcag 600

caaaattatg acacaattgc cagcggtaaa aataataact ggcatgtaca ctggtcagtt 660

attgcgaatg acttgaagta tggtggagaa gtgaaaaata gaaatgatga attattattc 720

tatagaaata cgagaattgc tactgtagaa aaccctgaac taagctttgc ttcaaaatat 780

agatacccag cattagtaag aagtggcttt aatccagaat ttttaactta tttatctaat 840

gaaaagtcaa atgagaaaac gcaatttgaa gtaacataca cacgaaatca agatattttg 900

aaaaacagac ctggaataca ttatgcacct tcaattttag aaaaaaataa agatggtcaa 960

aggttaattg tcacttatga agttgattgg aaaaataaaa cagttaaagt cgttgataaa 1020

tattctgatg acaataaacc ttataaagaa ggataa 1056

<210> 10

<211> 972

<212> DNA

<213> 人工序列

<220>

<223> LukG -克隆的DNA序列

<400> 10

tcagctcata aagactcgca agatcaaaat aagaaagaac atgttgataa gtctcaacaa 60

aaagacaaac gtaatgttac taataaagat aaaaattcaa cagtacctga tgatattggg 120

aaaaacggta aaatcacaaa acgaactgaa acagtatatg atgagaaaac aaatatactc 180

caaaatttac aattcgactt tatcgatgat ccaacttatg acaagaatgt attacttgtt 240

aaaaaacaag gctcaattca ttcaaattta aagtttgaat ctcataaaga agaaaaaaat 300

tcaaattggt taaagtatcc aagtgagtac catgtagatt ttcaagtaaa aagaaatcgt 360

aaaactgaaa tattagacca attgccgaaa aataaaattt caactgcgaa agtagacagt 420

acattttcat atagctcagg tggtaaattc gattcaacga aaggtattgg acgaacttca 480

tcaaatagct actccaaaac gattagttat aatcagcaaa attatgacac aattgccagc 540

ggtaaaaata ataactggca tgtacactgg tcagttattg cgaatgactt gaagtatggt 600

ggagaagtga aaaatagaaa tgatgaatta ttattctata gaaatacgag aattgctact 660

gtagaaaacc ctgaactaag ctttgcttca aaatatagat acccagcatt agtaagaagt 720

ggctttaatc cagaattttt aacttattta tctaatgaaa agtcaaatga gaaaacgcaa 780

tttgaagtaa catacacacg aaatcaagat attttgaaaa acagacctgg aatacattat 840

gcaccttcaa ttttagaaaa aaataaagat ggtcaaaggt taattgtcac ttatgaagtt 900

gattggaaaa ataaaacagt taaagtcgtt gataaatatt ctgatgacaa taaaccttat 960

aaagaaggat aa 972

<210> 11

<211> 351

<212> PRT

<213> 金黄色葡萄球菌

<400> 11

Met Lys Asn Lys Lys Arg Val Leu Ile Ala Ser Ser Leu Ser Cys Ala

1 5 10 15

Ile Leu Leu Leu Ser Ala Ala Thr Thr Gln Ala Asn Ser Ala His Lys

20 25 30

Asp Ser Gln Asp Gln Asn Lys Lys Glu His Val Asp Lys Ser Gln Gln

35 40 45

Lys Asp Lys Arg Asn Val Thr Asn Lys Asp Lys Asn Ser Thr Val Pro

50 55 60

Asp Asp Ile Gly Lys Asn Gly Lys Ile Thr Lys Arg Thr Glu Thr Val

65 70 75 80

Tyr Asp Glu Lys Thr Asn Ile Leu Gln Asn Leu Gln Phe Asp Phe Ile

85 90 95

Asp Asp Pro Thr Tyr Asp Lys Asn Val Leu Leu Val Lys Lys Gln Gly

100 105 110

Ser Ile His Ser Asn Leu Lys Phe Glu Ser His Lys Glu Glu Lys Asn

115 120 125

Ser Asn Trp Leu Lys Tyr Pro Ser Glu Tyr His Val Asp Phe Gln Val

130 135 140

Lys Arg Asn Arg Lys Thr Glu Ile Leu Asp Gln Leu Pro Lys Asn Lys

145 150 155 160

Ile Ser Thr Ala Lys Val Asp Ser Thr Phe Ser Tyr Ser Ser Gly Gly

165 170 175

Lys Phe Asp Ser Thr Lys Gly Ile Gly Arg Thr Ser Ser Asn Ser Tyr

180 185 190

Ser Lys Thr Ile Ser Tyr Asn Gln Gln Asn Tyr Asp Thr Ile Ala Ser

195 200 205

Gly Lys Asn Asn Asn Trp His Val His Trp Ser Val Ile Ala Asn Asp

210 215 220

Leu Lys Tyr Gly Gly Glu Val Lys Asn Arg Asn Asp Glu Leu Leu Phe

225 230 235 240

Tyr Arg Asn Thr Arg Ile Ala Thr Val Glu Asn Pro Glu Leu Ser Phe

245 250 255

Ala Ser Lys Tyr Arg Tyr Pro Ala Leu Val Arg Ser Gly Phe Asn Pro

260 265 270

Glu Phe Leu Thr Tyr Leu Ser Asn Glu Lys Ser Asn Glu Lys Thr Gln

275 280 285

Phe Glu Val Thr Tyr Thr Arg Asn Gln Asp Ile Leu Lys Asn Arg Pro

290 295 300

Gly Ile His Tyr Ala Pro Ser Ile Leu Glu Lys Asn Lys Asp Gly Gln

305 310 315 320

Arg Leu Ile Val Thr Tyr Glu Val Asp Trp Lys Asn Lys Thr Val Lys

325 330 335

Val Val Asp Lys Tyr Ser Asp Asp Asn Lys Pro Tyr Lys Glu Gly

340 345 350

<210> 12

<211> 323

<212> PRT

<213> 人工序列

<220>

<223> LukG -克隆的肽序列

<400> 12

Ser Ala His Lys Asp Ser Gln Asp Gln Asn Lys Lys Glu His Val Asp

1 5 10 15

Lys Ser Gln Gln Lys Asp Lys Arg Asn Val Thr Asn Lys Asp Lys Asn

20 25 30

Ser Thr Val Pro Asp Asp Ile Gly Lys Asn Gly Lys Ile Thr Lys Arg

35 40 45

Thr Glu Thr Val Tyr Asp Glu Lys Thr Asn Ile Leu Gln Asn Leu Gln

50 55 60

Phe Asp Phe Ile Asp Asp Pro Thr Tyr Asp Lys Asn Val Leu Leu Val

65 70 75 80

Lys Lys Gln Gly Ser Ile His Ser Asn Leu Lys Phe Glu Ser His Lys

85 90 95

Glu Glu Lys Asn Ser Asn Trp Leu Lys Tyr Pro Ser Glu Tyr His Val

100 105 110

Asp Phe Gln Val Lys Arg Asn Arg Lys Thr Glu Ile Leu Asp Gln Leu

115 120 125

Pro Lys Asn Lys Ile Ser Thr Ala Lys Val Asp Ser Thr Phe Ser Tyr

130 135 140

Ser Ser Gly Gly Lys Phe Asp Ser Thr Lys Gly Ile Gly Arg Thr Ser

145 150 155 160

Ser Asn Ser Tyr Ser Lys Thr Ile Ser Tyr Asn Gln Gln Asn Tyr Asp

165 170 175

Thr Ile Ala Ser Gly Lys Asn Asn Asn Trp His Val His Trp Ser Val

180 185 190

Ile Ala Asn Asp Leu Lys Tyr Gly Gly Glu Val Lys Asn Arg Asn Asp

195 200 205

Glu Leu Leu Phe Tyr Arg Asn Thr Arg Ile Ala Thr Val Glu Asn Pro

210 215 220

Glu Leu Ser Phe Ala Ser Lys Tyr Arg Tyr Pro Ala Leu Val Arg Ser

225 230 235 240

Gly Phe Asn Pro Glu Phe Leu Thr Tyr Leu Ser Asn Glu Lys Ser Asn

245 250 255

Glu Lys Thr Gln Phe Glu Val Thr Tyr Thr Arg Asn Gln Asp Ile Leu

260 265 270

Lys Asn Arg Pro Gly Ile His Tyr Ala Pro Ser Ile Leu Glu Lys Asn

275 280 285

Lys Asp Gly Gln Arg Leu Ile Val Thr Tyr Glu Val Asp Trp Lys Asn

290 295 300

Lys Thr Val Lys Val Val Asp Lys Tyr Ser Asp Asp Asn Lys Pro Tyr

305 310 315 320

Lys Glu Gly

<210> 13

<211> 1017

<212> DNA

<213> 金黄色葡萄球菌

<400> 13

atgattaaac aattatacaa aaacatcaca atttgtagtt tagcaatatc tactgcatta 60

actgtatttc cggcaacttc ttatgcaaaa attaattctg aaattaaagc tgtttctgag 120

aagaatcttg atggtgatac taaaatgtat acacgtacag ctacaacaag tgatagtcaa 180

aaaaatatta ctcaaagctt acaatttaat ttcttaactg aacctaatta tgataaagaa 240

acagtattta ttaaagcaaa aggtacaatt ggtagtggtt tgagaatttt agacccaaat 300

ggttattgga atagtacatt aagatggcct ggatcttatt cagtttcaat tcaaaatgtt 360

gatgacaaca acaatacaaa tgtgactgac tttgcaccaa aaaatcagga tgaatcaaga 420

gaagttaaat atacgtatgg ttataaaaca ggtggagatt tttcgattaa tcgtggaggc 480

ttaactggaa atattacaaa agagagtaat tattcagaga cgattagtta tcaacaacca 540

tcatatcgta cattacttga tcaatctacg tcacataaag gtgtaggttg gaaagtagaa 600

gcacatttga taaataatat gggacatgac catacgagac aattaactaa tgatagtgat 660

aatagaacta aaagtgaaat cttttcttta acacgaaatg gaaatttatg ggcgaaagat 720

aatttcacac ctaaagacaa aatgcctgta actgtgtctg aagggtttaa tccagaattt 780

ttagctgtta tgtcacatga taaaaaagac aaaggtaaat cacaatttgt tgttcattat 840

aaaagatcaa tggatgagtt taaaatagat tggaatcgcc atggtttctg gggctattgg 900

tctggtgaaa accatgtaga taaaaaagaa gaaaaattat cagcattata tgaagttgat 960

tggaagacac atgatgtgaa gtttgtaaaa gtacttaatg ataatgaaaa gaaataa 1017

<210> 14

<211> 927

<212> DNA

<213> 人工序列

<220>

<223> LukH -克隆的DNA序列

<400> 14

attaattctg aaattaaagc tgtttctgag aagaatcttg atggtgatac taaaatgtat 60

acacgtacag ctacaacaag tgatagtcaa aaaaatatta ctcaaagctt acaatttaat 120

ttcttaactg aacctaatta tgataaagaa acagtattta ttaaagcaaa aggtacaatt 180

ggtagtggtt tgagaatttt agacccaaat ggttattgga atagtacatt aagatggcct 240

ggatcttatt cagtttcaat tcaaaatgtt gatgacaaca acaatacaaa tgtgactgac 300

tttgcaccaa aaaatcagga tgaatcaaga gaagttaaat atacgtatgg ttataaaaca 360

ggtggagatt tttcgattaa tcgtggaggc ttaactggaa atattacaaa agagagtaat 420

tattcagaga cgattagtta tcaacaacca tcatatcgta cattacttga tcaatctacg 480

tcacataaag gtgtaggttg gaaagtagaa gcacatttga taaataatat gggacatgac 540

catacgagac aattaactaa tgatagtgat aatagaacta aaagtgaaat cttttcttta 600

acacgaaatg gaaatttatg ggcgaaagat aatttcacac ctaaagacaa aatgcctgta 660

actgtgtctg aagggtttaa tccagaattt ttagctgtta tgtcacatga taaaaaagac 720

aaaggtaaat cacaatttgt tgttcattat aaaagatcaa tggatgagtt taaaatagat 780

tggaatcgcc atggtttctg gggctattgg tctggtgaaa accatgtaga taaaaaagaa 840

gaaaaattat cagcattata tgaagttgat tggaagacac atgatgtgaa gtttgtaaaa 900

gtacttaatg ataatgaaaa gaaataa 927

<210> 15

<211> 338

<212> PRT

<213> 金黄色葡萄球菌

<400> 15

Met Ile Lys Gln Leu Tyr Lys Asn Ile Thr Ile Cys Ser Leu Ala Ile

1 5 10 15

Ser Thr Ala Leu Thr Val Phe Pro Ala Thr Ser Tyr Ala Lys Ile Asn

20 25 30

Ser Glu Ile Lys Ala Val Ser Glu Lys Asn Leu Asp Gly Asp Thr Lys

35 40 45

Met Tyr Thr Arg Thr Ala Thr Thr Ser Asp Ser Gln Lys Asn Ile Thr

50 55 60

Gln Ser Leu Gln Phe Asn Phe Leu Thr Glu Pro Asn Tyr Asp Lys Glu

65 70 75 80

Thr Val Phe Ile Lys Ala Lys Gly Thr Ile Gly Ser Gly Leu Arg Ile

85 90 95

Leu Asp Pro Asn Gly Tyr Trp Asn Ser Thr Leu Arg Trp Pro Gly Ser

100 105 110

Tyr Ser Val Ser Ile Gln Asn Val Asp Asp Asn Asn Asn Thr Asn Val

115 120 125

Thr Asp Phe Ala Pro Lys Asn Gln Asp Glu Ser Arg Glu Val Lys Tyr

130 135 140

Thr Tyr Gly Tyr Lys Thr Gly Gly Asp Phe Ser Ile Asn Arg Gly Gly

145 150 155 160

Leu Thr Gly Asn Ile Thr Lys Glu Ser Asn Tyr Ser Glu Thr Ile Ser

165 170 175

Tyr Gln Gln Pro Ser Tyr Arg Thr Leu Leu Asp Gln Ser Thr Ser His

180 185 190

Lys Gly Val Gly Trp Lys Val Glu Ala His Leu Ile Asn Asn Met Gly

195 200 205

His Asp His Thr Arg Gln Leu Thr Asn Asp Ser Asp Asn Arg Thr Lys

210 215 220

Ser Glu Ile Phe Ser Leu Thr Arg Asn Gly Asn Leu Trp Ala Lys Asp

225 230 235 240

Asn Phe Thr Pro Lys Asp Lys Met Pro Val Thr Val Ser Glu Gly Phe

245 250 255

Asn Pro Glu Phe Leu Ala Val Met Ser His Asp Lys Lys Asp Lys Gly

260 265 270

Lys Ser Gln Phe Val Val His Tyr Lys Arg Ser Met Asp Glu Phe Lys

275 280 285

Ile Asp Trp Asn Arg His Gly Phe Trp Gly Tyr Trp Ser Gly Glu Asn

290 295 300

His Val Asp Lys Lys Glu Glu Lys Leu Ser Ala Leu Tyr Glu Val Asp

305 310 315 320

Trp Lys Thr His Asp Val Lys Phe Val Lys Val Leu Asn Asp Asn Glu

325 330 335

Lys Lys

<210> 16

<211> 308

<212> PRT

<213> 人工序列

<220>

<223> LukH -克隆的肽序列

<400> 16

Ile Asn Ser Glu Ile Lys Ala Val Ser Glu Lys Asn Leu Asp Gly Asp

1 5 10 15

Thr Lys Met Tyr Thr Arg Thr Ala Thr Thr Ser Asp Ser Gln Lys Asn

20 25 30

Ile Thr Gln Ser Leu Gln Phe Asn Phe Leu Thr Glu Pro Asn Tyr Asp

35 40 45

Lys Glu Thr Val Phe Ile Lys Ala Lys Gly Thr Ile Gly Ser Gly Leu

50 55 60

Arg Ile Leu Asp Pro Asn Gly Tyr Trp Asn Ser Thr Leu Arg Trp Pro

65 70 75 80

Gly Ser Tyr Ser Val Ser Ile Gln Asn Val Asp Asp Asn Asn Asn Thr

85 90 95

Asn Val Thr Asp Phe Ala Pro Lys Asn Gln Asp Glu Ser Arg Glu Val

100 105 110

Lys Tyr Thr Tyr Gly Tyr Lys Thr Gly Gly Asp Phe Ser Ile Asn Arg

115 120 125

Gly Gly Leu Thr Gly Asn Ile Thr Lys Glu Ser Asn Tyr Ser Glu Thr

130 135 140

Ile Ser Tyr Gln Gln Pro Ser Tyr Arg Thr Leu Leu Asp Gln Ser Thr

145 150 155 160

Ser His Lys Gly Val Gly Trp Lys Val Glu Ala His Leu Ile Asn Asn

165 170 175

Met Gly His Asp His Thr Arg Gln Leu Thr Asn Asp Ser Asp Asn Arg

180 185 190

Thr Lys Ser Glu Ile Phe Ser Leu Thr Arg Asn Gly Asn Leu Trp Ala

195 200 205

Lys Asp Asn Phe Thr Pro Lys Asp Lys Met Pro Val Thr Val Ser Glu

210 215 220

Gly Phe Asn Pro Glu Phe Leu Ala Val Met Ser His Asp Lys Lys Asp

225 230 235 240

Lys Gly Lys Ser Gln Phe Val Val His Tyr Lys Arg Ser Met Asp Glu

245 250 255

Phe Lys Ile Asp Trp Asn Arg His Gly Phe Trp Gly Tyr Trp Ser Gly

260 265 270

Glu Asn His Val Asp Lys Lys Glu Glu Lys Leu Ser Ala Leu Tyr Glu

275 280 285

Val Asp Trp Lys Thr His Asp Val Lys Phe Val Lys Val Leu Asn Asp

290 295 300

Asn Glu Lys Lys

305

<210> 17

<211> 930

<212> DNA

<213> 金黄色葡萄球菌

<400> 17

atgaaaaaat tagtaccttt attattagcc ttattacttc tagttgctgc atgtggtact 60

ggtggtaaac aaagcagtga taagtcaaat ggcaaattaa aagtagtaac gacgaattca 120

attttatatg atatggctaa aaatgttggt ggagacaacg tcgatattca tagtattgta 180

cctgttggtc aagatcctca tgaatatgaa gttaaaccta aagatattaa aaagttaact 240

gacgctgacg ttattttata caacggatta aatttagaga ctggtaacgg ttggtttgaa 300

aaagccttag aacaggctgg taaatcatta aaagataaaa aagttatcgc agtatcaaaa 360

gatgttaaac ctatctattt aaacggtgaa gaaggcaaca aagataaaca agatccacac 420

gcatggttaa gtttagataa tggtattaaa tacgtaaaaa caattcaaca aacatttatc 480

gataacgaca aaaaacataa agcagattat gaaaagcaag gtaacaaata cattgctcaa 540

ttggaaaaat taaataatga cagtaaagac aaatttaatg acattccaaa agaacaacgt 600

gccatgatta caagtgaagg tgccttcaag tacttctcaa aacaatacgg tattacacca 660

ggttatattt gggaaattaa cactgaaaaa caaggtacac ctgaacaaat gagacaagct 720

attgagtttg ttaaaaagca caaattaaaa cacttattag tagaaacaag tgttgataag 780

aaagcaatgg aaagtttatc tgaagaaacg aagaaagata tctttggtga agtgtacaca 840

gattcaatcg gtaaagaagg cactaaaggt gactcttact acaaaatgat gaaatcaaat 900

attgaaactg tacacggaag catgaaataa 930

<210> 18

<211> 831

<212> DNA

<213> 人工序列

<220>

<223> MntC -克隆的DNA序列

<400> 18

aaagtagtaa cgacgaattc aattttatat gatatggcta aaaatgttgg tggagacaac 60

gtcgatattc atagtattgt acctgttggt caagatcctc atgaatatga agttaaacct 120

aaagatatta aaaagttaac tgacgctgac gttattttat acaacggatt aaatttagag 180

actggtaacg gttggtttga aaaagcctta gaacaggctg gtaaatcatt aaaagataaa 240

aaagttatcg cagtatcaaa agatgttaaa cctatctatt taaacggtga agaaggcaac 300

aaagataaac aagatccaca cgcatggtta agtttagata atggtattaa atacgtaaaa 360

acaattcaac aaacatttat cgataacgac aaaaaacata aagcagatta tgaaaagcaa 420

ggtaacaaat acattgctca attggaaaaa ttaaataatg acagtaaaga caaatttaat 480

gacattccaa aagaacaacg tgccatgatt acaagtgaag gtgccttcaa gtacttctca 540

aaacaatacg gtattacacc aggttatatt tgggaaatta acactgaaaa acaaggtaca 600

cctgaacaaa tgagacaagc tattgagttt gttaaaaagc acaaattaaa acacttatta 660

gtagaaacaa gtgttgataa gaaagcaatg gaaagtttat ctgaagaaac gaagaaagat 720

atctttggtg aagtgtacac agattcaatc ggtaaagaag gcactaaagg tgactcttac 780

tacaaaatga tgaaatcaaa tattgaaact gtacacggaa gcatgaaata a 831

<210> 19

<211> 309

<212> PRT

<213> 金黄色葡萄球菌

<400> 19

Met Lys Lys Leu Val Pro Leu Leu Leu Ala Leu Leu Leu Leu Val Ala

1 5 10 15

Ala Cys Gly Thr Gly Gly Lys Gln Ser Ser Asp Lys Ser Asn Gly Lys

20 25 30

Leu Lys Val Val Thr Thr Asn Ser Ile Leu Tyr Asp Met Ala Lys Asn

35 40 45

Val Gly Gly Asp Asn Val Asp Ile His Ser Ile Val Pro Val Gly Gln

50 55 60

Asp Pro His Glu Tyr Glu Val Lys Pro Lys Asp Ile Lys Lys Leu Thr

65 70 75 80

Asp Ala Asp Val Ile Leu Tyr Asn Gly Leu Asn Leu Glu Thr Gly Asn

85 90 95

Gly Trp Phe Glu Lys Ala Leu Glu Gln Ala Gly Lys Ser Leu Lys Asp

100 105 110

Lys Lys Val Ile Ala Val Ser Lys Asp Val Lys Pro Ile Tyr Leu Asn

115 120 125

Gly Glu Glu Gly Asn Lys Asp Lys Gln Asp Pro His Ala Trp Leu Ser

130 135 140

Leu Asp Asn Gly Ile Lys Tyr Val Lys Thr Ile Gln Gln Thr Phe Ile

145 150 155 160

Asp Asn Asp Lys Lys His Lys Ala Asp Tyr Glu Lys Gln Gly Asn Lys

165 170 175

Tyr Ile Ala Gln Leu Glu Lys Leu Asn Asn Asp Ser Lys Asp Lys Phe

180 185 190

Asn Asp Ile Pro Lys Glu Gln Arg Ala Met Ile Thr Ser Glu Gly Ala

195 200 205

Phe Lys Tyr Phe Ser Lys Gln Tyr Gly Ile Thr Pro Gly Tyr Ile Trp

210 215 220

Glu Ile Asn Thr Glu Lys Gln Gly Thr Pro Glu Gln Met Arg Gln Ala

225 230 235 240

Ile Glu Phe Val Lys Lys His Lys Leu Lys His Leu Leu Val Glu Thr

245 250 255

Ser Val Asp Lys Lys Ala Met Glu Ser Leu Ser Glu Glu Thr Lys Lys

260 265 270

Asp Ile Phe Gly Glu Val Tyr Thr Asp Ser Ile Gly Lys Glu Gly Thr

275 280 285

Lys Gly Asp Ser Tyr Tyr Lys Met Met Lys Ser Asn Ile Glu Thr Val

290 295 300

His Gly Ser Met Lys

305

<210> 20

<211> 276

<212> PRT

<213> 人工序列

<220>

<223> MntC -克隆的肽序列

<400> 20

Lys Val Val Thr Thr Asn Ser Ile Leu Tyr Asp Met Ala Lys Asn Val

1 5 10 15

Gly Gly Asp Asn Val Asp Ile His Ser Ile Val Pro Val Gly Gln Asp

20 25 30

Pro His Glu Tyr Glu Val Lys Pro Lys Asp Ile Lys Lys Leu Thr Asp

35 40 45

Ala Asp Val Ile Leu Tyr Asn Gly Leu Asn Leu Glu Thr Gly Asn Gly

50 55 60

Trp Phe Glu Lys Ala Leu Glu Gln Ala Gly Lys Ser Leu Lys Asp Lys

65 70 75 80

Lys Val Ile Ala Val Ser Lys Asp Val Lys Pro Ile Tyr Leu Asn Gly

85 90 95

Glu Glu Gly Asn Lys Asp Lys Gln Asp Pro His Ala Trp Leu Ser Leu

100 105 110

Asp Asn Gly Ile Lys Tyr Val Lys Thr Ile Gln Gln Thr Phe Ile Asp

115 120 125

Asn Asp Lys Lys His Lys Ala Asp Tyr Glu Lys Gln Gly Asn Lys Tyr

130 135 140

Ile Ala Gln Leu Glu Lys Leu Asn Asn Asp Ser Lys Asp Lys Phe Asn

145 150 155 160

Asp Ile Pro Lys Glu Gln Arg Ala Met Ile Thr Ser Glu Gly Ala Phe

165 170 175

Lys Tyr Phe Ser Lys Gln Tyr Gly Ile Thr Pro Gly Tyr Ile Trp Glu

180 185 190

Ile Asn Thr Glu Lys Gln Gly Thr Pro Glu Gln Met Arg Gln Ala Ile

195 200 205

Glu Phe Val Lys Lys His Lys Leu Lys His Leu Leu Val Glu Thr Ser

210 215 220

Val Asp Lys Lys Ala Met Glu Ser Leu Ser Glu Glu Thr Lys Lys Asp

225 230 235 240

Ile Phe Gly Glu Val Tyr Thr Asp Ser Ile Gly Lys Glu Gly Thr Lys

245 250 255

Gly Asp Ser Tyr Tyr Lys Met Met Lys Ser Asn Ile Glu Thr Val His

260 265 270

Gly Ser Met Lys

275

<210> 21

<211> 2076

<212> DNA

<213> 金黄色葡萄球菌

<400> 21

atgttaagag gacaagaaga aagaaagtat agtattagaa agtattcaat aggcgtggtg 60

tcagtgttag cggctacaat gtttgttgtg tcatcacatg aagcacaagc ctcggaaaaa 120

acaccaacgt ccaatgcagc ggcacaaaaa gaaacactaa atcaaccggg agaacaaggg 180

aacgcgataa cgtcacatca aatgcagtca ggaaagcaat tagacgatat gcataaagag 240

aatggtaaaa gtggaacagt gacagaaggt aaagacacgc ttcaatcatc gaagcatcaa 300

tcaacacaaa atagtaaaac aatcagaacg caaaatgata atcaagtaaa gcaagattct 360

gaacgacaag gttctaaaca gtcacaccaa aataatgcga ctaataatac tgaacgtcaa 420

aatgatcagg ttcaaaatac ccatcatgct gaacgtaatg gatcacaatc gacaacgtca 480

caatcgaatg atgttgataa atcacaacca tccattccgg cacaaaaggt attacccaat 540

catgataaag cagcaccaac ttcaactaca cccccgtcta atgataaaac tgcacctaaa 600

tcaacaaaag cacaagatgc aaccacggac aaacatccaa atcaacaaga tacacatcaa 660

cccgcgcatc aaatcataga tgcaaagcaa gatgatactg ttcgccaaag tgaacagaaa 720

ccacaagttg gcgatttaag taaacatatc gatggtcaaa attccccaga gaaaccgaca 780

gataaaaata ctgataataa acaactaatc aaagatgcgc ttcaagcgcc taaaacacgt 840

tcgactacaa atgcagcagc agatgctaaa aaggttcgac cacttaaagc gaatcaagta 900

caaccactta acaaatatcc agttgttttt gtacatggat ttttaggatt agtaggcgat 960

aatgcacctg ctttatatcc aaattattgg ggtggaaata aatttaaagt tatcgaggaa 1020

ttgagaaagc aaggctataa tgtacatcaa gcaagtgtaa gtgcatttgg tagtaactat 1080

gatcgcgctg tagaacttta ttattacatt aaaggtggtc gcgtagatta tggcgcagca 1140

catgcagcta aatacggaca tgagcgctat ggtaagactt ataaaggaat catgcctaat 1200

tgggaacctg gtaaaaaggt acatcttgta gggcatagta tgggtggtca aacaattcgt 1260

ttaatggaag agtttttaag aaatggtaac aaagaagaaa ttgcctatca taaagcgcat 1320

ggtggagaaa tatcaccatt attcactggt ggtcataaca atatggttgc atcaatcaca 1380

acattagcaa caccacataa tggttcacaa gcagctgata agtttggaaa tacagaagct 1440

gttagaaaaa tcatgttcgc tttaaatcga tttatgggta acaagtattc gaatatcgat 1500

ttaggattaa cgcaatgggg ctttaaacaa ttaccaaatg agagttacat tgactatata 1560

aaacgcgtta gtaaaagcaa aatttggaca tcagacgata atgctgccta tgatttaacg 1620

ttagatggct ctgcaaaatt gaacaacatg acaagtatga atcctaatat tacgtatacg 1680

acttatacag gtgtgtcttc acatactggt ccattaggtt atgaaaatcc tgatttaggt 1740

acatttttct taatggatac aacgagtaga attattggtc atgatgcaag agaagaatgg 1800

cgtaaaaatg atggtgtcgt accagtgatt tcgtcgttac atccatccaa tcaaccattt 1860

attaatgtta cgaatgatga acctgccaca cgcagaggta tctggcaagt taaaccaatc 1920

atacaaggat gggatcatgt cgattttatc ggtgtggact tcctggattt caaacgtaaa 1980

ggtgcagaac ttgccaactt ctatacaggt attataaatg acttgttgcg tgtggaagcg 2040

actgaaagta aaggaacaca attgaaagca agttaa 2076

<210> 22

<211> 1962

<212> DNA

<213> 人工序列

<220>

<223> Lip2 -克隆的DNA序列

<400> 22

gaaaaaacac caacgtccaa tgcagcggca caaaaagaaa cactaaatca accgggagaa 60

caagggaacg cgataacgtc acatcaaatg cagtcaggaa agcaattaga cgatatgcat 120

aaagagaatg gtaaaagtgg aacagtgaca gaaggtaaag acacgcttca atcatcgaag 180

catcaatcaa cacaaaatag taaaacaatc agaacgcaaa atgataatca agtaaagcaa 240

gattctgaac gacaaggttc taaacagtca caccaaaata atgcgactaa taatactgaa 300

cgtcaaaatg atcaggttca aaatacccat catgctgaac gtaatggatc acaatcgaca 360

acgtcacaat cgaatgatgt tgataaatca caaccatcca ttccggcaca aaaggtatta 420

cccaatcatg ataaagcagc accaacttca actacacccc cgtctaatga taaaactgca 480

cctaaatcaa caaaagcaca agatgcaacc acggacaaac atccaaatca acaagataca 540

catcaacccg cgcatcaaat catagatgca aagcaagatg atactgttcg ccaaagtgaa 600

cagaaaccac aagttggcga tttaagtaaa catatcgatg gtcaaaattc cccagagaaa 660

ccgacagata aaaatactga taataaacaa ctaatcaaag atgcgcttca agcgcctaaa 720

acacgttcga ctacaaatgc agcagcagat gctaaaaagg ttcgaccact taaagcgaat 780

caagtacaac cacttaacaa atatccagtt gtttttgtac atggattttt aggattagta 840

ggcgataatg cacctgcttt atatccaaat tattggggtg gaaataaatt taaagttatc 900

gaggaattga gaaagcaagg ctataatgta catcaagcaa gtgtaagtgc atttggtagt 960

aactatgatc gcgctgtaga actttattat tacattaaag gtggtcgcgt agattatggc 1020

gcagcacatg cagctaaata cggacatgag cgctatggta agacttataa aggaatcatg 1080

cctaattggg aacctggtaa aaaggtacat cttgtagggc atagtatggg tggtcaaaca 1140

attcgtttaa tggaagagtt tttaagaaat ggtaacaaag aagaaattgc ctatcataaa 1200

gcgcatggtg gagaaatatc accattattc actggtggtc ataacaatat ggttgcatca 1260

atcacaacat tagcaacacc acataatggt tcacaagcag ctgataagtt tggaaataca 1320

gaagctgtta gaaaaatcat gttcgcttta aatcgattta tgggtaacaa gtattcgaat 1380

atcgatttag gattaacgca atggggcttt aaacaattac caaatgagag ttacattgac 1440

tatataaaac gcgttagtaa aagcaaaatt tggacatcag acgataatgc tgcctatgat 1500

ttaacgttag atggctctgc aaaattgaac aacatgacaa gtatgaatcc taatattacg 1560

tatacgactt atacaggtgt gtcttcacat actggtccat taggttatga aaatcctgat 1620

ttaggtacat ttttcttaat ggatacaacg agtagaatta ttggtcatga tgcaagagaa 1680

gaatggcgta aaaatgatgg tgtcgtacca gtgatttcgt cgttacatcc atccaatcaa 1740

ccatttatta atgttacgaa tgatgaacct gccacacgca gaggtatctg gcaagttaaa 1800

ccaatcatac aaggatggga tcatgtcgat tttatcggtg tggacttcct ggatttcaaa 1860

cgtaaaggtg cagaacttgc caacttctat acaggtatta taaatgactt gttgcgtgtg 1920

gaagcgactg aaagtaaagg aacacaattg aaagcaagtt aa 1962

<210> 23

<211> 691

<212> PRT

<213> 金黄色葡萄球菌

<400> 23

Met Leu Arg Gly Gln Glu Glu Arg Lys Tyr Ser Ile Arg Lys Tyr Ser

1 5 10 15

Ile Gly Val Val Ser Val Leu Ala Ala Thr Met Phe Val Val Ser Ser

20 25 30

His Glu Ala Gln Ala Ser Glu Lys Thr Pro Thr Ser Asn Ala Ala Ala

35 40 45

Gln Lys Glu Thr Leu Asn Gln Pro Gly Glu Gln Gly Asn Ala Ile Thr

50 55 60

Ser His Gln Met Gln Ser Gly Lys Gln Leu Asp Asp Met His Lys Glu

65 70 75 80

Asn Gly Lys Ser Gly Thr Val Thr Glu Gly Lys Asp Thr Leu Gln Ser

85 90 95

Ser Lys His Gln Ser Thr Gln Asn Ser Lys Thr Ile Arg Thr Gln Asn

100 105 110

Asp Asn Gln Val Lys Gln Asp Ser Glu Arg Gln Gly Ser Lys Gln Ser

115 120 125

His Gln Asn Asn Ala Thr Asn Asn Thr Glu Arg Gln Asn Asp Gln Val

130 135 140

Gln Asn Thr His His Ala Glu Arg Asn Gly Ser Gln Ser Thr Thr Ser

145 150 155 160

Gln Ser Asn Asp Val Asp Lys Ser Gln Pro Ser Ile Pro Ala Gln Lys

165 170 175

Val Leu Pro Asn His Asp Lys Ala Ala Pro Thr Ser Thr Thr Pro Pro

180 185 190

Ser Asn Asp Lys Thr Ala Pro Lys Ser Thr Lys Ala Gln Asp Ala Thr

195 200 205

Thr Asp Lys His Pro Asn Gln Gln Asp Thr His Gln Pro Ala His Gln

210 215 220

Ile Ile Asp Ala Lys Gln Asp Asp Thr Val Arg Gln Ser Glu Gln Lys

225 230 235 240

Pro Gln Val Gly Asp Leu Ser Lys His Ile Asp Gly Gln Asn Ser Pro

245 250 255

Glu Lys Pro Thr Asp Lys Asn Thr Asp Asn Lys Gln Leu Ile Lys Asp

260 265 270

Ala Leu Gln Ala Pro Lys Thr Arg Ser Thr Thr Asn Ala Ala Ala Asp

275 280 285

Ala Lys Lys Val Arg Pro Leu Lys Ala Asn Gln Val Gln Pro Leu Asn

290 295 300

Lys Tyr Pro Val Val Phe Val His Gly Phe Leu Gly Leu Val Gly Asp

305 310 315 320

Asn Ala Pro Ala Leu Tyr Pro Asn Tyr Trp Gly Gly Asn Lys Phe Lys

325 330 335

Val Ile Glu Glu Leu Arg Lys Gln Gly Tyr Asn Val His Gln Ala Ser

340 345 350

Val Ser Ala Phe Gly Ser Asn Tyr Asp Arg Ala Val Glu Leu Tyr Tyr

355 360 365

Tyr Ile Lys Gly Gly Arg Val Asp Tyr Gly Ala Ala His Ala Ala Lys

370 375 380

Tyr Gly His Glu Arg Tyr Gly Lys Thr Tyr Lys Gly Ile Met Pro Asn

385 390 395 400

Trp Glu Pro Gly Lys Lys Val His Leu Val Gly His Ser Met Gly Gly

405 410 415

Gln Thr Ile Arg Leu Met Glu Glu Phe Leu Arg Asn Gly Asn Lys Glu

420 425 430

Glu Ile Ala Tyr His Lys Ala His Gly Gly Glu Ile Ser Pro Leu Phe

435 440 445

Thr Gly Gly His Asn Asn Met Val Ala Ser Ile Thr Thr Leu Ala Thr

450 455 460

Pro His Asn Gly Ser Gln Ala Ala Asp Lys Phe Gly Asn Thr Glu Ala

465 470 475 480

Val Arg Lys Ile Met Phe Ala Leu Asn Arg Phe Met Gly Asn Lys Tyr

485 490 495

Ser Asn Ile Asp Leu Gly Leu Thr Gln Trp Gly Phe Lys Gln Leu Pro

500 505 510

Asn Glu Ser Tyr Ile Asp Tyr Ile Lys Arg Val Ser Lys Ser Lys Ile

515 520 525

Trp Thr Ser Asp Asp Asn Ala Ala Tyr Asp Leu Thr Leu Asp Gly Ser

530 535 540

Ala Lys Leu Asn Asn Met Thr Ser Met Asn Pro Asn Ile Thr Tyr Thr

545 550 555 560

Thr Tyr Thr Gly Val Ser Ser His Thr Gly Pro Leu Gly Tyr Glu Asn

565 570 575

Pro Asp Leu Gly Thr Phe Phe Leu Met Asp Thr Thr Ser Arg Ile Ile

580 585 590

Gly His Asp Ala Arg Glu Glu Trp Arg Lys Asn Asp Gly Val Val Pro

595 600 605

Val Ile Ser Ser Leu His Pro Ser Asn Gln Pro Phe Ile Asn Val Thr

610 615 620

Asn Asp Glu Pro Ala Thr Arg Arg Gly Ile Trp Gln Val Lys Pro Ile

625 630 635 640

Ile Gln Gly Trp Asp His Val Asp Phe Ile Gly Val Asp Phe Leu Asp

645 650 655

Phe Lys Arg Lys Gly Ala Glu Leu Ala Asn Phe Tyr Thr Gly Ile Ile

660 665 670

Asn Asp Leu Leu Arg Val Glu Ala Thr Glu Ser Lys Gly Thr Gln Leu

675 680 685

Lys Ala Ser

690

<210> 24

<211> 653

<212> PRT

<213> 人工序列

<220>

<223> Lip2 -克隆的肽序列

<400> 24

Glu Lys Thr Pro Thr Ser Asn Ala Ala Ala Gln Lys Glu Thr Leu Asn

1 5 10 15

Gln Pro Gly Glu Gln Gly Asn Ala Ile Thr Ser His Gln Met Gln Ser

20 25 30

Gly Lys Gln Leu Asp Asp Met His Lys Glu Asn Gly Lys Ser Gly Thr

35 40 45

Val Thr Glu Gly Lys Asp Thr Leu Gln Ser Ser Lys His Gln Ser Thr

50 55 60

Gln Asn Ser Lys Thr Ile Arg Thr Gln Asn Asp Asn Gln Val Lys Gln

65 70 75 80

Asp Ser Glu Arg Gln Gly Ser Lys Gln Ser His Gln Asn Asn Ala Thr

85 90 95

Asn Asn Thr Glu Arg Gln Asn Asp Gln Val Gln Asn Thr His His Ala

100 105 110

Glu Arg Asn Gly Ser Gln Ser Thr Thr Ser Gln Ser Asn Asp Val Asp

115 120 125

Lys Ser Gln Pro Ser Ile Pro Ala Gln Lys Val Leu Pro Asn His Asp

130 135 140

Lys Ala Ala Pro Thr Ser Thr Thr Pro Pro Ser Asn Asp Lys Thr Ala

145 150 155 160

Pro Lys Ser Thr Lys Ala Gln Asp Ala Thr Thr Asp Lys His Pro Asn

165 170 175

Gln Gln Asp Thr His Gln Pro Ala His Gln Ile Ile Asp Ala Lys Gln

180 185 190

Asp Asp Thr Val Arg Gln Ser Glu Gln Lys Pro Gln Val Gly Asp Leu

195 200 205

Ser Lys His Ile Asp Gly Gln Asn Ser Pro Glu Lys Pro Thr Asp Lys

210 215 220

Asn Thr Asp Asn Lys Gln Leu Ile Lys Asp Ala Leu Gln Ala Pro Lys

225 230 235 240

Thr Arg Ser Thr Thr Asn Ala Ala Ala Asp Ala Lys Lys Val Arg Pro

245 250 255

Leu Lys Ala Asn Gln Val Gln Pro Leu Asn Lys Tyr Pro Val Val Phe

260 265 270

Val His Gly Phe Leu Gly Leu Val Gly Asp Asn Ala Pro Ala Leu Tyr

275 280 285

Pro Asn Tyr Trp Gly Gly Asn Lys Phe Lys Val Ile Glu Glu Leu Arg

290 295 300

Lys Gln Gly Tyr Asn Val His Gln Ala Ser Val Ser Ala Phe Gly Ser

305 310 315 320

Asn Tyr Asp Arg Ala Val Glu Leu Tyr Tyr Tyr Ile Lys Gly Gly Arg

325 330 335

Val Asp Tyr Gly Ala Ala His Ala Ala Lys Tyr Gly His Glu Arg Tyr

340 345 350

Gly Lys Thr Tyr Lys Gly Ile Met Pro Asn Trp Glu Pro Gly Lys Lys

355 360 365

Val His Leu Val Gly His Ser Met Gly Gly Gln Thr Ile Arg Leu Met

370 375 380

Glu Glu Phe Leu Arg Asn Gly Asn Lys Glu Glu Ile Ala Tyr His Lys

385 390 395 400

Ala His Gly Gly Glu Ile Ser Pro Leu Phe Thr Gly Gly His Asn Asn

405 410 415

Met Val Ala Ser Ile Thr Thr Leu Ala Thr Pro His Asn Gly Ser Gln

420 425 430

Ala Ala Asp Lys Phe Gly Asn Thr Glu Ala Val Arg Lys Ile Met Phe

435 440 445

Ala Leu Asn Arg Phe Met Gly Asn Lys Tyr Ser Asn Ile Asp Leu Gly

450 455 460

Leu Thr Gln Trp Gly Phe Lys Gln Leu Pro Asn Glu Ser Tyr Ile Asp

465 470 475 480

Tyr Ile Lys Arg Val Ser Lys Ser Lys Ile Trp Thr Ser Asp Asp Asn

485 490 495

Ala Ala Tyr Asp Leu Thr Leu Asp Gly Ser Ala Lys Leu Asn Asn Met

500 505 510

Thr Ser Met Asn Pro Asn Ile Thr Tyr Thr Thr Tyr Thr Gly Val Ser

515 520 525

Ser His Thr Gly Pro Leu Gly Tyr Glu Asn Pro Asp Leu Gly Thr Phe

530 535 540

Phe Leu Met Asp Thr Thr Ser Arg Ile Ile Gly His Asp Ala Arg Glu

545 550 555 560

Glu Trp Arg Lys Asn Asp Gly Val Val Pro Val Ile Ser Ser Leu His

565 570 575

Pro Ser Asn Gln Pro Phe Ile Asn Val Thr Asn Asp Glu Pro Ala Thr

580 585 590

Arg Arg Gly Ile Trp Gln Val Lys Pro Ile Ile Gln Gly Trp Asp His

595 600 605

Val Asp Phe Ile Gly Val Asp Phe Leu Asp Phe Lys Arg Lys Gly Ala

610 615 620

Glu Leu Ala Asn Phe Tyr Thr Gly Ile Ile Asn Asp Leu Leu Arg Val

625 630 635 640

Glu Ala Thr Glu Ser Lys Gly Thr Gln Leu Lys Ala Ser

645 650

<210> 25

<211> 1488

<212> DNA

<213> 金黄色葡萄球菌

<400> 25

atgagagaaa attttaaatt acgtaaaatg aaagtcggtt tagtatcagt tgcaattact 60

atgttatata tcatgacaaa cggacaagct gaagcatctg aaactaatca gaaggtaagt 120

acaaatcaag aatcaaaagc tgtttcgcag actgaacaaa attccaaaga aacaaaagcg 180

gcagagtctt ctaaaaactt tgtaaattta gatcctatca aaccaggagc tcaaaaagta 240

acaggtacta cattaccgaa tcatattatt ttacttaata tagatggtaa aagtgctgat 300

tcagttgaag gaggatatgg tgattttata actgcaaatg acaaaggaga gtttgagtat 360

cctttaaata atcgtaaaat tgtccataac caagaaattg aggtatcatc atcaagccct 420

gatttaggtg acgatgaaga ggatgaagaa gtagaagaat cttcaactga aaaagctggt 480

gctgaggaag aaagtacaga tgctaaagct acatatacaa caccacgata tgaaaaagcg 540

tatgaaatac cgaaagaaca actaaaagaa aaagatggac accaccaagt tttcatcgaa 600

ccaattactg aaggttcagg tattattaaa ggtcatacgt ctgtaaaagg taaagttgct 660

ctatctatta ataataaatt tattaatttt gaagaaagag ctaaaggtgg aattagtaaa 720

gaagatacta aagctagttc cgatggtgtt tggatgccta ttaatgaaaa aggatatttt 780

gattttgatt tcaaaaaaaa tccttttgat aacttagagt taaagaaaaa tgatgaaatc 840

tcattaacat ttgcacctga tgatgaagat gaagcattga agtcattaat tttcaaaact 900

aaagtaacga gcttagaaga tatcgataaa gcagaaacaa aatatgacca tactaaagtg 960

gaaaaagtaa aagtattgaa agatgttaaa gaagatatac atgtagatga aatttacgga 1020

agcttatatc atacagaaaa aggtaaaggt attcttgata aacaaggaac taaagagatt 1080

acagggaaga ctaaattcgc gaatgcagta gtgaaagtat attctgactt aggtgatgcg 1140

caattgttcc ctgatattca agtagatgaa aatggtaaat ttagctttga tgctgaaaaa 1200

gctggtttca gattgcaaaa tggagaaaca ttgaattttg cagtagttaa acctattact 1260

ggtgacctat tacatcaagg atttgtctct aaatatattg atgtatatga atctccggaa 1320

gaaaagaaag aacgtgaatt tgaagaaaaa cttgaaaaca cgcctgcata tcataaatta 1380

catggtgata aaattgtagg atatgatgtt caaggtaatc catcaacttg gttctatcca 1440

ttaggtgaaa agaaagttga acgtacaaca cctaaattag aaaaataa 1488

<210> 26

<211> 1392

<212> DNA

<213> 人工序列

<220>

<223> 推定的 -克隆的DNA序列

<400> 26

tctgaaacta atcagaaggt aagtacaaat caagaatcaa aagctgtttc gcagactgaa 60

caaaattcca aagaaacaaa agcggcagag tcttctaaaa actttgtaaa tttagatcct 120

atcaaaccag gagctcaaaa agtaacaggt actacattac cgaatcatat tattttactt 180

aatatagatg gtaaaagtgc tgattcagtt gaaggaggat atggtgattt tataactgca 240

aatgacaaag gagagtttga gtatccttta aataatcgta aaattgtcca taaccaagaa 300

attgaggtat catcatcaag ccctgattta ggtgacgatg aagaggatga agaagtagaa 360

gaatcttcaa ctgaaaaagc tggtgctgag gaagaaagta cagatgctaa agctacatat 420

acaacaccac gatatgaaaa agcgtatgaa ataccgaaag aacaactaaa agaaaaagat 480

ggacaccacc aagttttcat cgaaccaatt actgaaggtt caggtattat taaaggtcat 540

acgtctgtaa aaggtaaagt tgctctatct attaataata aatttattaa ttttgaagaa 600

agagctaaag gtggaattag taaagaagat actaaagcta gttccgatgg tgtttggatg 660

cctattaatg aaaaaggata ttttgatttt gatttcaaaa aaaatccttt tgataactta 720

gagttaaaga aaaatgatga aatctcatta acatttgcac ctgatgatga agatgaagca 780

ttgaagtcat taattttcaa aactaaagta acgagcttag aagatatcga taaagcagaa 840

acaaaatatg accatactaa agtggaaaaa gtaaaagtat tgaaagatgt taaagaagat 900

atacatgtag atgaaattta cggaagctta tatcatacag aaaaaggtaa aggtattctt 960

gataaacaag gaactaaaga gattacaggg aagactaaat tcgcgaatgc agtagtgaaa 1020

gtatattctg acttaggtga tgcgcaattg ttccctgata ttcaagtaga tgaaaatggt 1080

aaatttagct ttgatgctga aaaagctggt ttcagattgc aaaatggaga aacattgaat 1140

tttgcagtag ttaaacctat tactggtgac ctattacatc aaggatttgt ctctaaatat 1200

attgatgtat atgaatctcc ggaagaaaag aaagaacgtg aatttgaaga aaaacttgaa 1260

aacacgcctg catatcataa attacatggt gataaaattg taggatatga tgttcaaggt 1320

aatccatcaa cttggttcta tccattaggt gaaaagaaag ttgaacgtac aacacctaaa 1380

ttagaaaaat aa 1392

<210> 27

<211> 495

<212> PRT

<213> 金黄色葡萄球菌

<400> 27

Met Arg Glu Asn Phe Lys Leu Arg Lys Met Lys Val Gly Leu Val Ser

1 5 10 15

Val Ala Ile Thr Met Leu Tyr Ile Met Thr Asn Gly Gln Ala Glu Ala

20 25 30

Ser Glu Thr Asn Gln Lys Val Ser Thr Asn Gln Glu Ser Lys Ala Val

35 40 45

Ser Gln Thr Glu Gln Asn Ser Lys Glu Thr Lys Ala Ala Glu Ser Ser

50 55 60

Lys Asn Phe Val Asn Leu Asp Pro Ile Lys Pro Gly Ala Gln Lys Val

65 70 75 80

Thr Gly Thr Thr Leu Pro Asn His Ile Ile Leu Leu Asn Ile Asp Gly

85 90 95

Lys Ser Ala Asp Ser Val Glu Gly Gly Tyr Gly Asp Phe Ile Thr Ala

100 105 110

Asn Asp Lys Gly Glu Phe Glu Tyr Pro Leu Asn Asn Arg Lys Ile Val

115 120 125

His Asn Gln Glu Ile Glu Val Ser Ser Ser Ser Pro Asp Leu Gly Asp

130 135 140

Asp Glu Glu Asp Glu Glu Val Glu Glu Ser Ser Thr Glu Lys Ala Gly

145 150 155 160

Ala Glu Glu Glu Ser Thr Asp Ala Lys Ala Thr Tyr Thr Thr Pro Arg

165 170 175

Tyr Glu Lys Ala Tyr Glu Ile Pro Lys Glu Gln Leu Lys Glu Lys Asp

180 185 190

Gly His His Gln Val Phe Ile Glu Pro Ile Thr Glu Gly Ser Gly Ile

195 200 205

Ile Lys Gly His Thr Ser Val Lys Gly Lys Val Ala Leu Ser Ile Asn

210 215 220

Asn Lys Phe Ile Asn Phe Glu Glu Arg Ala Lys Gly Gly Ile Ser Lys

225 230 235 240

Glu Asp Thr Lys Ala Ser Ser Asp Gly Val Trp Met Pro Ile Asn Glu

245 250 255

Lys Gly Tyr Phe Asp Phe Asp Phe Lys Lys Asn Pro Phe Asp Asn Leu

260 265 270

Glu Leu Lys Lys Asn Asp Glu Ile Ser Leu Thr Phe Ala Pro Asp Asp

275 280 285

Glu Asp Glu Ala Leu Lys Ser Leu Ile Phe Lys Thr Lys Val Thr Ser

290 295 300

Leu Glu Asp Ile Asp Lys Ala Glu Thr Lys Tyr Asp His Thr Lys Val

305 310 315 320

Glu Lys Val Lys Val Leu Lys Asp Val Lys Glu Asp Ile His Val Asp

325 330 335

Glu Ile Tyr Gly Ser Leu Tyr His Thr Glu Lys Gly Lys Gly Ile Leu

340 345 350

Asp Lys Gln Gly Thr Lys Glu Ile Thr Gly Lys Thr Lys Phe Ala Asn

355 360 365

Ala Val Val Lys Val Tyr Ser Asp Leu Gly Asp Ala Gln Leu Phe Pro

370 375 380

Asp Ile Gln Val Asp Glu Asn Gly Lys Phe Ser Phe Asp Ala Glu Lys

385 390 395 400

Ala Gly Phe Arg Leu Gln Asn Gly Glu Thr Leu Asn Phe Ala Val Val

405 410 415

Lys Pro Ile Thr Gly Asp Leu Leu His Gln Gly Phe Val Ser Lys Tyr

420 425 430

Ile Asp Val Tyr Glu Ser Pro Glu Glu Lys Lys Glu Arg Glu Phe Glu

435 440 445

Glu Lys Leu Glu Asn Thr Pro Ala Tyr His Lys Leu His Gly Asp Lys

450 455 460

Ile Val Gly Tyr Asp Val Gln Gly Asn Pro Ser Thr Trp Phe Tyr Pro

465 470 475 480

Leu Gly Glu Lys Lys Val Glu Arg Thr Thr Pro Lys Leu Glu Lys

485 490 495

<210> 28

<211> 463

<212> PRT

<213> 人工序列

<220>

<223> 推定的 -克隆的肽序列

<400> 28

Ser Glu Thr Asn Gln Lys Val Ser Thr Asn Gln Glu Ser Lys Ala Val

1 5 10 15

Ser Gln Thr Glu Gln Asn Ser Lys Glu Thr Lys Ala Ala Glu Ser Ser

20 25 30

Lys Asn Phe Val Asn Leu Asp Pro Ile Lys Pro Gly Ala Gln Lys Val

35 40 45

Thr Gly Thr Thr Leu Pro Asn His Ile Ile Leu Leu Asn Ile Asp Gly

50 55 60

Lys Ser Ala Asp Ser Val Glu Gly Gly Tyr Gly Asp Phe Ile Thr Ala

65 70 75 80

Asn Asp Lys Gly Glu Phe Glu Tyr Pro Leu Asn Asn Arg Lys Ile Val

85 90 95

His Asn Gln Glu Ile Glu Val Ser Ser Ser Ser Pro Asp Leu Gly Asp

100 105 110

Asp Glu Glu Asp Glu Glu Val Glu Glu Ser Ser Thr Glu Lys Ala Gly

115 120 125

Ala Glu Glu Glu Ser Thr Asp Ala Lys Ala Thr Tyr Thr Thr Pro Arg

130 135 140

Tyr Glu Lys Ala Tyr Glu Ile Pro Lys Glu Gln Leu Lys Glu Lys Asp

145 150 155 160

Gly His His Gln Val Phe Ile Glu Pro Ile Thr Glu Gly Ser Gly Ile

165 170 175

Ile Lys Gly His Thr Ser Val Lys Gly Lys Val Ala Leu Ser Ile Asn

180 185 190

Asn Lys Phe Ile Asn Phe Glu Glu Arg Ala Lys Gly Gly Ile Ser Lys

195 200 205

Glu Asp Thr Lys Ala Ser Ser Asp Gly Val Trp Met Pro Ile Asn Glu

210 215 220

Lys Gly Tyr Phe Asp Phe Asp Phe Lys Lys Asn Pro Phe Asp Asn Leu

225 230 235 240

Glu Leu Lys Lys Asn Asp Glu Ile Ser Leu Thr Phe Ala Pro Asp Asp

245 250 255

Glu Asp Glu Ala Leu Lys Ser Leu Ile Phe Lys Thr Lys Val Thr Ser

260 265 270

Leu Glu Asp Ile Asp Lys Ala Glu Thr Lys Tyr Asp His Thr Lys Val

275 280 285

Glu Lys Val Lys Val Leu Lys Asp Val Lys Glu Asp Ile His Val Asp

290 295 300

Glu Ile Tyr Gly Ser Leu Tyr His Thr Glu Lys Gly Lys Gly Ile Leu

305 310 315 320

Asp Lys Gln Gly Thr Lys Glu Ile Thr Gly Lys Thr Lys Phe Ala Asn

325 330 335

Ala Val Val Lys Val Tyr Ser Asp Leu Gly Asp Ala Gln Leu Phe Pro

340 345 350

Asp Ile Gln Val Asp Glu Asn Gly Lys Phe Ser Phe Asp Ala Glu Lys

355 360 365

Ala Gly Phe Arg Leu Gln Asn Gly Glu Thr Leu Asn Phe Ala Val Val

370 375 380

Lys Pro Ile Thr Gly Asp Leu Leu His Gln Gly Phe Val Ser Lys Tyr

385 390 395 400

Ile Asp Val Tyr Glu Ser Pro Glu Glu Lys Lys Glu Arg Glu Phe Glu

405 410 415

Glu Lys Leu Glu Asn Thr Pro Ala Tyr His Lys Leu His Gly Asp Lys

420 425 430

Ile Val Gly Tyr Asp Val Gln Gly Asn Pro Ser Thr Trp Phe Tyr Pro

435 440 445

Leu Gly Glu Lys Lys Val Glu Arg Thr Thr Pro Lys Leu Glu Lys

450 455 460

<210> 29

<211> 3747

<212> DNA

<213> 金黄色葡萄球菌

<400> 29

atggcgaaaa aattcaatta caaactacca tcaatggttg cattaacgct tgtaggttca 60

gcagtcactg cacatcaagt tcaagcagct gagacgacac aagatcaaac tactaataaa 120

aatgttttag atagtaataa agttaaagca actactgaac aagcaaaagc tgaggtaaaa 180

aatccaacgc aaaacatttc tggcactcaa gtatatcaag accctgctat tgtccaacca 240

aaaacagcaa ataacaaaac aggcaatgct caagtaagtc aaaaagttga tactgcacaa 300

gtaaatggtg acactcgtgc taatcaatca gcgactacaa ataatacgca gcctgttgca 360

aagtcaacaa gcactacagc acctaaaact aacactaatg ttacaaatgc tggttatagt 420

ttagttgatg atgaagatga taattcagaa catcaaatta atccagaatt aattaaatca 480

gctgctaaac ctgcagctct tgaaacgcaa tataaagccg cagcacctaa agctaaaact 540

gaagcgacac ctaaagtaac tacttttagc gcttcagcac aaccaagatc agttgctgca 600

acaccaaaaa cgagtttgcc aaaatataaa ccacaagtaa actcttcaat taacgattac 660

attcgtaaaa ataacttaaa agcacctaaa attgaagaag attatacatc ttacttccct 720

aaatacgcat accgtaacgg cgtaggtcgt cctgaaggta tcgtagttca tgatacagct 780

aatgatcgtt cgacgataaa tggtgaaatt agttatatga aaaataacta tcaaaacgca 840

ttcgtacatg catttgttga tggggatcgt ataatcgaaa cagcaccaac ggattactta 900

tcttggggtg tcggtgcagt cggtaaccct agattcatca atgttgaaat cgtacacaca 960

cacgactatg cttcatttgc acgttcaatg aataactatg ctgactatgc agctacacaa 1020

ttacaatatt atggtttaaa accagacagt gctgagtatg atggaaatgg tacagtatgg 1080

actcactacg ctgtaagtaa atatttaggt ggtacggacc atgccgatcc acatggatat 1140

ttaagaagtc ataattatag ttatgatcaa ttatatgact taattaatga aaaatattta 1200

ataaaaatgg gtaaagtggc gccatggggt acgcaattta caactacccc tactacacca 1260

tcaaaaccaa caacaccgtc gaaaccatca actggtaaat taacagttgc agcaaacaat 1320

ggtgtcgcac aaatcaaacc aacaaatagt ggtttatata ctactgttta cgacaaaact 1380

ggtaaagcaa ctaatgaagt tcaaaaaaca tttgctgtat ctaaaacagc tacattaggt 1440

aatcaaaaat tctatcttgt tcaagattac aattctggta ataaatttgg ttgggttaaa 1500

gaaggcgatg tggtttacaa cacagctaaa tcacctgtaa atgtaaatca atcatattca 1560

atcaaatctg gtacgaaact ttatacagta ccttggggta catctaaaca agttgctggt 1620

agcgtgtctg gctctggaaa ccaaacattt aaggcttcaa agcaacaaca aattgataaa 1680

tcaatttatt tatatggctc tgtgaatggt aaatctggtt gggtaagtaa agcatattta 1740

gttgatactg ctaaacctac gcctacacca atacctaagc catcaacacc tacaacaaat 1800

aataaattaa cagtttcatc attaaacggt gttgctcaaa ttaatgctaa aaacaatggc 1860

ttattcacta cagtttatga caaaactggt aagccaacga aagaagttca aaaaacattt 1920

gctgtaacaa aagaagcaag tttaggtgga aacaaattct acttagttaa agattacaat 1980

agtccaactt taattggttg ggttaaacaa ggtgacgtta tttataacaa tgcaaaatca 2040

cctgtaaatg taatgcaaac atatacagta aaaccaggca ctaaattata ttcagtacct 2100

tggggcactt ataaacaaga agctggtgca gtttctggta caggtaacca aacttttaaa 2160

gcgactaagc aacaacaaat tgataaatct atctatttat ttggaactgt aaatggtaaa 2220

tctggttggg taagtaaagc atatttagct gtacctgctg cacctaaaaa agcagtagca 2280

caaccaaaaa cagctgtaaa agcttatact gttactaaac cacaaacgac tcaaacagtt 2340

agcaagattg ctcaagttaa accaaacaac actggtattc gtgcttctgt ttatgaaaaa 2400

acagcgaaaa acggtgcgaa atatgcagac cgtacgttct atgtaacaaa agagcgtgct 2460

catggtaatg aaacgtatgt attattaaac aatacaagcc ataacatccc attaggttgg 2520

ttcaatgtaa aagacttaaa tgttcaaaac ctaggcaaag aagttaaaac gactcaaaaa 2580

tatactgtta ataaatcaaa taacggctta tcaatggttc cttggggtac taaaaaccaa 2640

gtcattttaa caggcaataa cattgctcaa ggtacattta atgcaacgaa acaagtatct 2700

gtaggcaaag atgtttattt atacggtact attaataacc gcactggttg ggtaaatgca 2760

aaagatttaa ctgcaccaac tgctgtgaaa ccaactacat cagctgccaa agattataac 2820

tacacttatg taattaaaaa tggtaatggt tattactatg taacaccaaa ttctgataca 2880

gctaaatact cattaaaagc atttaatgaa caaccattcg cagttgttaa agaacaagtc 2940

attaatggac aaacttggta ctatggtaaa ttatctaacg gtaaattagc atggattaaa 3000

tcaactgatt tagctaaaga attaattaag tataatcaaa caggtatgac attaaaccaa 3060

gttgctcaaa tacaagctgg tttacaatat aaaccacaag tacaacgtgt accaggtaag 3120

tggacagatg ctaactttaa tgatgttaag catgcaatgg atacgaagcg tttagctcaa 3180

gatccagcat taaaatatca attcttacgc ttagaccaac cacaaaatat ttctattgat 3240

aaaattaatc aattcttaaa aggtaaaggt gtattagaaa accaaggtgc tgcatttaac 3300

aaagctgctc aaatgtatgg cattaatgaa gtttatctta tctcacatgc cctattagaa 3360

acaggtaacg gtacttctca attagcgaaa ggtgcagatg tagtgaacaa caaagttgta 3420

actaactcaa acacgaaata ccataacgta tttggtattg ctgcatatga taacgatcct 3480

ttacgtgaag gtattaaata tgctaaacaa gctggttggg acacagtatc aaaagcaatc 3540

gttggtggtg ctaaattcat cggcaactca tatgtaaaag ctggtcaaaa tacactttac 3600

aaaatgagat ggaatcctgc acatccagga acacaccaat atgctacaga tgtagattgg 3660

gctaacatca atgctaaaat catcaaaggc tactatgata aaattggcga agtcggcaaa 3720

tacttcgaca tcccacaata taaataa 3747

<210> 30

<211> 576

<212> DNA

<213> 人工序列

<220>

<223> Atl -克隆的DNA序列

<400> 30

tcaaaaccaa caacaccgtc gaaaccatca actggtaaat taacagttgc agcaaacaat 60

ggtgtcgcac aaatcaaacc aacaaatagt ggtttatata ctactgttta cgacaaaact 120

ggtaaagcaa ctaatgaagt tcaaaaaaca tttgctgtat ctaaaacagc tacattaggt 180

aatcaaaaat tctatcttgt tcaagattac aattctggta ataaatttgg ttgggttaaa 240

gaaggcgatg tggtttacaa cacagctaaa tcacctgtaa atgtaaatca atcatattca 300

atcaaatctg gtacgaaact ttatacagta ccttggggta catctaaaca agttgctggt 360

agcgtgtctg gctctggaaa ccaaacattt aaggcttcaa agcaacaaca aattgataaa 420

tcaatttatt tatatggctc tgtgaatggt aaatctggtt gggtaagtaa agcatattta 480

gttgatactg ctaaacctac gcctacacca atacctaagc catcaacacc tacaacaaat 540

aataaattaa cagtttcatc attaaacggt aaataa 576

<210> 31

<211> 1248

<212> PRT

<213> 金黄色葡萄球菌

<400> 31

Met Ala Lys Lys Phe Asn Tyr Lys Leu Pro Ser Met Val Ala Leu Thr

1 5 10 15

Leu Val Gly Ser Ala Val Thr Ala His Gln Val Gln Ala Ala Glu Thr

20 25 30

Thr Gln Asp Gln Thr Thr Asn Lys Asn Val Leu Asp Ser Asn Lys Val

35 40 45

Lys Ala Thr Thr Glu Gln Ala Lys Ala Glu Val Lys Asn Pro Thr Gln

50 55 60

Asn Ile Ser Gly Thr Gln Val Tyr Gln Asp Pro Ala Ile Val Gln Pro

65 70 75 80

Lys Thr Ala Asn Asn Lys Thr Gly Asn Ala Gln Val Ser Gln Lys Val

85 90 95

Asp Thr Ala Gln Val Asn Gly Asp Thr Arg Ala Asn Gln Ser Ala Thr

100 105 110

Thr Asn Asn Thr Gln Pro Val Ala Lys Ser Thr Ser Thr Thr Ala Pro

115 120 125

Lys Thr Asn Thr Asn Val Thr Asn Ala Gly Tyr Ser Leu Val Asp Asp

130 135 140

Glu Asp Asp Asn Ser Glu His Gln Ile Asn Pro Glu Leu Ile Lys Ser

145 150 155 160

Ala Ala Lys Pro Ala Ala Leu Glu Thr Gln Tyr Lys Ala Ala Ala Pro

165 170 175

Lys Ala Lys Thr Glu Ala Thr Pro Lys Val Thr Thr Phe Ser Ala Ser

180 185 190

Ala Gln Pro Arg Ser Val Ala Ala Thr Pro Lys Thr Ser Leu Pro Lys

195 200 205

Tyr Lys Pro Gln Val Asn Ser Ser Ile Asn Asp Tyr Ile Arg Lys Asn

210 215 220

Asn Leu Lys Ala Pro Lys Ile Glu Glu Asp Tyr Thr Ser Tyr Phe Pro

225 230 235 240

Lys Tyr Ala Tyr Arg Asn Gly Val Gly Arg Pro Glu Gly Ile Val Val

245 250 255

His Asp Thr Ala Asn Asp Arg Ser Thr Ile Asn Gly Glu Ile Ser Tyr

260 265 270

Met Lys Asn Asn Tyr Gln Asn Ala Phe Val His Ala Phe Val Asp Gly

275 280 285

Asp Arg Ile Ile Glu Thr Ala Pro Thr Asp Tyr Leu Ser Trp Gly Val

290 295 300

Gly Ala Val Gly Asn Pro Arg Phe Ile Asn Val Glu Ile Val His Thr

305 310 315 320

His Asp Tyr Ala Ser Phe Ala Arg Ser Met Asn Asn Tyr Ala Asp Tyr

325 330 335

Ala Ala Thr Gln Leu Gln Tyr Tyr Gly Leu Lys Pro Asp Ser Ala Glu

340 345 350

Tyr Asp Gly Asn Gly Thr Val Trp Thr His Tyr Ala Val Ser Lys Tyr

355 360 365

Leu Gly Gly Thr Asp His Ala Asp Pro His Gly Tyr Leu Arg Ser His

370 375 380

Asn Tyr Ser Tyr Asp Gln Leu Tyr Asp Leu Ile Asn Glu Lys Tyr Leu

385 390 395 400

Ile Lys Met Gly Lys Val Ala Pro Trp Gly Thr Gln Phe Thr Thr Thr

405 410 415

Pro Thr Thr Pro Ser Lys Pro Thr Thr Pro Ser Lys Pro Ser Thr Gly

420 425 430

Lys Leu Thr Val Ala Ala Asn Asn Gly Val Ala Gln Ile Lys Pro Thr

435 440 445

Asn Ser Gly Leu Tyr Thr Thr Val Tyr Asp Lys Thr Gly Lys Ala Thr

450 455 460

Asn Glu Val Gln Lys Thr Phe Ala Val Ser Lys Thr Ala Thr Leu Gly

465 470 475 480

Asn Gln Lys Phe Tyr Leu Val Gln Asp Tyr Asn Ser Gly Asn Lys Phe

485 490 495

Gly Trp Val Lys Glu Gly Asp Val Val Tyr Asn Thr Ala Lys Ser Pro

500 505 510

Val Asn Val Asn Gln Ser Tyr Ser Ile Lys Ser Gly Thr Lys Leu Tyr

515 520 525

Thr Val Pro Trp Gly Thr Ser Lys Gln Val Ala Gly Ser Val Ser Gly

530 535 540

Ser Gly Asn Gln Thr Phe Lys Ala Ser Lys Gln Gln Gln Ile Asp Lys

545 550 555 560

Ser Ile Tyr Leu Tyr Gly Ser Val Asn Gly Lys Ser Gly Trp Val Ser

565 570 575

Lys Ala Tyr Leu Val Asp Thr Ala Lys Pro Thr Pro Thr Pro Ile Pro

580 585 590

Lys Pro Ser Thr Pro Thr Thr Asn Asn Lys Leu Thr Val Ser Ser Leu

595 600 605

Asn Gly Val Ala Gln Ile Asn Ala Lys Asn Asn Gly Leu Phe Thr Thr

610 615 620

Val Tyr Asp Lys Thr Gly Lys Pro Thr Lys Glu Val Gln Lys Thr Phe

625 630 635 640

Ala Val Thr Lys Glu Ala Ser Leu Gly Gly Asn Lys Phe Tyr Leu Val

645 650 655

Lys Asp Tyr Asn Ser Pro Thr Leu Ile Gly Trp Val Lys Gln Gly Asp

660 665 670

Val Ile Tyr Asn Asn Ala Lys Ser Pro Val Asn Val Met Gln Thr Tyr

675 680 685

Thr Val Lys Pro Gly Thr Lys Leu Tyr Ser Val Pro Trp Gly Thr Tyr

690 695 700

Lys Gln Glu Ala Gly Ala Val Ser Gly Thr Gly Asn Gln Thr Phe Lys

705 710 715 720

Ala Thr Lys Gln Gln Gln Ile Asp Lys Ser Ile Tyr Leu Phe Gly Thr

725 730 735

Val Asn Gly Lys Ser Gly Trp Val Ser Lys Ala Tyr Leu Ala Val Pro

740 745 750

Ala Ala Pro Lys Lys Ala Val Ala Gln Pro Lys Thr Ala Val Lys Ala

755 760 765

Tyr Thr Val Thr Lys Pro Gln Thr Thr Gln Thr Val Ser Lys Ile Ala

770 775 780

Gln Val Lys Pro Asn Asn Thr Gly Ile Arg Ala Ser Val Tyr Glu Lys

785 790 795 800

Thr Ala Lys Asn Gly Ala Lys Tyr Ala Asp Arg Thr Phe Tyr Val Thr

805 810 815

Lys Glu Arg Ala His Gly Asn Glu Thr Tyr Val Leu Leu Asn Asn Thr

820 825 830

Ser His Asn Ile Pro Leu Gly Trp Phe Asn Val Lys Asp Leu Asn Val

835 840 845

Gln Asn Leu Gly Lys Glu Val Lys Thr Thr Gln Lys Tyr Thr Val Asn

850 855 860

Lys Ser Asn Asn Gly Leu Ser Met Val Pro Trp Gly Thr Lys Asn Gln

865 870 875 880

Val Ile Leu Thr Gly Asn Asn Ile Ala Gln Gly Thr Phe Asn Ala Thr

885 890 895

Lys Gln Val Ser Val Gly Lys Asp Val Tyr Leu Tyr Gly Thr Ile Asn

900 905 910

Asn Arg Thr Gly Trp Val Asn Ala Lys Asp Leu Thr Ala Pro Thr Ala

915 920 925

Val Lys Pro Thr Thr Ser Ala Ala Lys Asp Tyr Asn Tyr Thr Tyr Val

930 935 940

Ile Lys Asn Gly Asn Gly Tyr Tyr Tyr Val Thr Pro Asn Ser Asp Thr

945 950 955 960

Ala Lys Tyr Ser Leu Lys Ala Phe Asn Glu Gln Pro Phe Ala Val Val

965 970 975

Lys Glu Gln Val Ile Asn Gly Gln Thr Trp Tyr Tyr Gly Lys Leu Ser

980 985 990

Asn Gly Lys Leu Ala Trp Ile Lys Ser Thr Asp Leu Ala Lys Glu Leu

995 1000 1005

Ile Lys Tyr Asn Gln Thr Gly Met Thr Leu Asn Gln Val Ala Gln

1010 1015 1020

Ile Gln Ala Gly Leu Gln Tyr Lys Pro Gln Val Gln Arg Val Pro

1025 1030 1035

Gly Lys Trp Thr Asp Ala Asn Phe Asn Asp Val Lys His Ala Met

1040 1045 1050

Asp Thr Lys Arg Leu Ala Gln Asp Pro Ala Leu Lys Tyr Gln Phe

1055 1060 1065

Leu Arg Leu Asp Gln Pro Gln Asn Ile Ser Ile Asp Lys Ile Asn

1070 1075 1080

Gln Phe Leu Lys Gly Lys Gly Val Leu Glu Asn Gln Gly Ala Ala

1085 1090 1095

Phe Asn Lys Ala Ala Gln Met Tyr Gly Ile Asn Glu Val Tyr Leu

1100 1105 1110

Ile Ser His Ala Leu Leu Glu Thr Gly Asn Gly Thr Ser Gln Leu

1115 1120 1125

Ala Lys Gly Ala Asp Val Val Asn Asn Lys Val Val Thr Asn Ser

1130 1135 1140

Asn Thr Lys Tyr His Asn Val Phe Gly Ile Ala Ala Tyr Asp Asn

1145 1150 1155

Asp Pro Leu Arg Glu Gly Ile Lys Tyr Ala Lys Gln Ala Gly Trp

1160 1165 1170

Asp Thr Val Ser Lys Ala Ile Val Gly Gly Ala Lys Phe Ile Gly

1175 1180 1185

Asn Ser Tyr Val Lys Ala Gly Gln Asn Thr Leu Tyr Lys Met Arg

1190 1195 1200

Trp Asn Pro Ala His Pro Gly Thr His Gln Tyr Ala Thr Asp Val

1205 1210 1215

Asp Trp Ala Asn Ile Asn Ala Lys Ile Ile Lys Gly Tyr Tyr Asp

1220 1225 1230

Lys Ile Gly Glu Val Gly Lys Tyr Phe Asp Ile Pro Gln Tyr Lys

1235 1240 1245

<210> 32

<211> 191

<212> PRT

<213> 人工序列

<220>

<223> Atl -克隆的肽序列

<400> 32

Ser Lys Pro Thr Thr Pro Ser Lys Pro Ser Thr Gly Lys Leu Thr Val

1 5 10 15

Ala Ala Asn Asn Gly Val Ala Gln Ile Lys Pro Thr Asn Ser Gly Leu

20 25 30

Tyr Thr Thr Val Tyr Asp Lys Thr Gly Lys Ala Thr Asn Glu Val Gln

35 40 45

Lys Thr Phe Ala Val Ser Lys Thr Ala Thr Leu Gly Asn Gln Lys Phe

50 55 60

Tyr Leu Val Gln Asp Tyr Asn Ser Gly Asn Lys Phe Gly Trp Val Lys

65 70 75 80

Glu Gly Asp Val Val Tyr Asn Thr Ala Lys Ser Pro Val Asn Val Asn

85 90 95

Gln Ser Tyr Ser Ile Lys Ser Gly Thr Lys Leu Tyr Thr Val Pro Trp

100 105 110

Gly Thr Ser Lys Gln Val Ala Gly Ser Val Ser Gly Ser Gly Asn Gln

115 120 125

Thr Phe Lys Ala Ser Lys Gln Gln Gln Ile Asp Lys Ser Ile Tyr Leu

130 135 140

Tyr Gly Ser Val Asn Gly Lys Ser Gly Trp Val Ser Lys Ala Tyr Leu

145 150 155 160

Val Asp Thr Ala Lys Pro Thr Pro Thr Pro Ile Pro Lys Pro Ser Thr

165 170 175

Pro Thr Thr Asn Asn Lys Leu Thr Val Ser Ser Leu Asn Gly Lys

180 185 190

<210> 33

<211> 435

<212> DNA

<213> 金黄色葡萄球菌

<400> 33

atgaaattaa aatcatttat aactgtaact ttggcactgg gcatgatcgc aacgactggc 60

gctactgtga caagtaatga ggtatctgca gcagaaaagg acaaactacc ggcaactcaa 120

aaagctaaag aaatgcaaaa tgttccatat acaattgcag tagatggcat tatggctttc 180

aatcaatctt acttaaattt accaaaagat agccaattat catatttaga tttaggaaat 240

aaagttaaag ctttattata tgatgaacgt ggtgtaacac ctgagaagat tcgaaatgca 300

aaatctgccg tttacacgat tacttggaaa gatggtagta aaaaagaagt ggatcttaag 360

aaagatagct acacagcaaa cttgtttgat tcaaattcaa ttaaacaaat tgatattaat 420

gtaaaaacta aataa 435

<210> 34

<211> 339

<212> DNA

<213> 人工序列

<220>

<223> 假设的 -克隆的DNA序列

<400> 34

aaggacaaac taccggcaac tcaaaaagct aaagaaatgc aaaatgttcc atatacaatt 60

gcagtagatg gcattatggc tttcaatcaa tcttacttaa atttaccaaa agatagccaa 120

ttatcatatt tagatttagg aaataaagtt aaagctttat tatatgatga acgtggtgta 180

acacctgaga agattcgaaa tgcaaaatct gccgtttaca cgattacttg gaaagatggt 240

agtaaaaaag aagtggatct taagaaagat agctacacag caaacttgtt tgattcaaat 300

tcaattaaac aaattgatat taatgtaaaa actaaataa 339

<210> 35

<211> 144

<212> PRT

<213> 金黄色葡萄球菌

<400> 35

Met Lys Leu Lys Ser Phe Ile Thr Val Thr Leu Ala Leu Gly Met Ile

1 5 10 15

Ala Thr Thr Gly Ala Thr Val Thr Ser Asn Glu Val Ser Ala Ala Glu

20 25 30

Lys Asp Lys Leu Pro Ala Thr Gln Lys Ala Lys Glu Met Gln Asn Val

35 40 45

Pro Tyr Thr Ile Ala Val Asp Gly Ile Met Ala Phe Asn Gln Ser Tyr

50 55 60

Leu Asn Leu Pro Lys Asp Ser Gln Leu Ser Tyr Leu Asp Leu Gly Asn

65 70 75 80

Lys Val Lys Ala Leu Leu Tyr Asp Glu Arg Gly Val Thr Pro Glu Lys

85 90 95

Ile Arg Asn Ala Lys Ser Ala Val Tyr Thr Ile Thr Trp Lys Asp Gly

100 105 110

Ser Lys Lys Glu Val Asp Leu Lys Lys Asp Ser Tyr Thr Ala Asn Leu

115 120 125

Phe Asp Ser Asn Ser Ile Lys Gln Ile Asp Ile Asn Val Lys Thr Lys

130 135 140

<210> 36

<211> 112

<212> PRT

<213> 人工序列

<220>

<223> 假设的-克隆的肽序列

<400> 36

Lys Asp Lys Leu Pro Ala Thr Gln Lys Ala Lys Glu Met Gln Asn Val

1 5 10 15

Pro Tyr Thr Ile Ala Val Asp Gly Ile Met Ala Phe Asn Gln Ser Tyr

20 25 30

Leu Asn Leu Pro Lys Asp Ser Gln Leu Ser Tyr Leu Asp Leu Gly Asn

35 40 45

Lys Val Lys Ala Leu Leu Tyr Asp Glu Arg Gly Val Thr Pro Glu Lys

50 55 60

Ile Arg Asn Ala Lys Ser Ala Val Tyr Thr Ile Thr Trp Lys Asp Gly

65 70 75 80

Ser Lys Lys Glu Val Asp Leu Lys Lys Asp Ser Tyr Thr Ala Asn Leu

85 90 95

Phe Asp Ser Asn Ser Ile Lys Gln Ile Asp Ile Asn Val Lys Thr Lys

100 105 110

<210> 37

<211> 2007

<212> DNA

<213> 金黄色葡萄球菌

<400> 37

atgaaaaaga taaaaattgt tccacttatt ttaatagttg tagttgtcgg gtttggtata 60

tatttttatg cttccaaaga taaagaaatt aataatacta ttgatgcaat tgaagataaa 120

aatttcaaac aagtttataa agatagcagt tatatttcta aaagcgataa tggtgaagta 180

gaaatgactg aacgtccgat aaaaatatat aatagtttag gcgttaaaga tataaacatt 240

caggatcgta aaataaaaaa agtatctaaa aataaaaaac gagtagatgc tcaatataaa 300

attaaaacaa actacggtaa cattgatcgc aacgttcaat ttaattttgt taaagaagat 360

ggtatgtgga agttagattg ggatcatagc gtcattattc caggaatgca gaaagaccaa 420

agcatacata ttgaaaattt aaaatcagaa cgtggtaaaa ttttagaccg aaacaatgtg 480

gaattggcca atacaggaac agcatatgag ataggcatcg ttccaaagaa tgtatctaaa 540

aaagattata aagcaatcgc taaagaacta agtatttctg aagactatat caaacaacaa 600

atggatcaaa attgggtaca agatgatacc ttcgttccac ttaaaaccgt taaaaaaatg 660

gatgaatatt taagtgattt cgcaaaaaaa tttcatctta caactaatga aacagaaagt 720

cgtaactatc ctctaggaaa agcgacttca catctattag gttatgttgg tcccattaac 780

tctgaagaat taaaacaaaa agaatataaa ggctataaag atgatgcagt tattggtaaa 840

aagggactcg aaaaacttta cgataaaaag ctccaacatg aagatggcta tcgtgtcaca 900

atcgttgacg ataatagcaa tacaatcgca catacattaa tagagaaaaa gaaaaaagat 960

ggcaaagata ttcaactaac tattgatgct aaagttcaaa agagtattta taacaacatg 1020

aaaaatgatt atggctcagg tactgctatc caccctcaaa caggtgaatt attagcactt 1080

gtaagcacac cttcatatga cgtctatcca tttatgtatg gcatgagtaa cgaagaatat 1140

aataaattaa ccgaagataa aaaagaacct ctgctcaaca agttccagat tacaacttca 1200

ccaggttcaa ctcaaaaaat attaacagca atgattgggt taaataacaa aacattagac 1260

gataaaacaa gttataaaat cgatggtaaa ggttggcaaa aagataaatc ttggggtggt 1320

tacaacgtta caagatatga agtggtaaat ggtaatatcg acttaaaaca agcaatagaa 1380

tcatcagata acattttctt tgctagagta gcactcgaat taggcagtaa gaaatttgaa 1440

aaaggcatga aaaaactagg tgttggtgaa gatataccaa gtgattatcc attttataat 1500

gctcaaattt caaacaaaaa tttagataat gaaatattat tagctgattc aggttacgga 1560

caaggtgaaa tactgattaa cccagtacag atcctttcaa tctatagcgc attagaaaat 1620

aatggcaata ttaacgcacc tcacttatta aaagacacga aaaacaaagt ttggaagaaa 1680

aatattattt ccaaagaaaa tatcaatcta ttaactgatg gtatgcaaca agtcgtaaat 1740

aaaacacata aagaagatat ttatagatct tatgcaaact taattggcaa atccggtact 1800

gcagaactca aaatgaaaca aggagaaact ggcagacaaa ttgggtggtt tatatcatat 1860

gataaagata atccaaacat gatgatggct attaatgtta aagatgtaca agataaagga 1920

atggctagct acaatgccaa aatctcaggt aaagtgtatg atgagctata tgagaacggt 1980

aataaaaaat acgatataga tgaataa 2007

<210> 38

<211> 1932

<212> DNA

<213> 人工序列

<220>

<223> Pbp2a -克隆的DNA序列

<400> 38

aaagataaag aaattaataa tactattgat gcaattgaag ataaaaattt caaacaagtt 60

tataaagata gcagttatat ttctaaaagc gataatggtg aagtagaaat gactgaacgt 120

ccgataaaaa tatataatag tttaggcgtt aaagatataa acattcagga tcgtaaaata 180

aaaaaagtat ctaaaaataa aaaacgagta gatgctcaat ataaaattaa aacaaactac 240

ggtaacattg atcgcaacgt tcaatttaat tttgttaaag aagatggtat gtggaagtta 300

gattgggatc atagcgtcat tattccagga atgcagaaag accaaagcat acatattgaa 360

aatttaaaat cagaacgtgg taaaatttta gaccgaaaca atgtggaatt ggccaataca 420

ggaacagcat atgagatagg catcgttcca aagaatgtat ctaaaaaaga ttataaagca 480

atcgctaaag aactaagtat ttctgaagac tatatcaaac aacaaatgga tcaaaattgg 540

gtacaagatg ataccttcgt tccacttaaa accgttaaaa aaatggatga atatttaagt 600

gatttcgcaa aaaaatttca tcttacaact aatgaaacag aaagtcgtaa ctatcctcta 660

ggaaaagcga cttcacatct attaggttat gttggtccca ttaactctga agaattaaaa 720

caaaaagaat ataaaggcta taaagatgat gcagttattg gtaaaaaggg actcgaaaaa 780

ctttacgata aaaagctcca acatgaagat ggctatcgtg tcacaatcgt tgacgataat 840

agcaatacaa tcgcacatac attaatagag aaaaagaaaa aagatggcaa agatattcaa 900

ctaactattg atgctaaagt tcaaaagagt atttataaca acatgaaaaa tgattatggc 960

tcaggtactg ctatccaccc tcaaacaggt gaattattag cacttgtaag cacaccttca 1020

tatgacgtct atccatttat gtatggcatg agtaacgaag aatataataa attaaccgaa 1080

gataaaaaag aacctctgct caacaagttc cagattacaa cttcaccagg ttcaactcaa 1140

aaaatattaa cagcaatgat tgggttaaat aacaaaacat tagacgataa aacaagttat 1200

aaaatcgatg gtaaaggttg gcaaaaagat aaatcttggg gtggttacaa cgttacaaga 1260

tatgaagtgg taaatggtaa tatcgactta aaacaagcaa tagaatcatc agataacatt 1320

ttctttgcta gagtagcact cgaattaggc agtaagaaat ttgaaaaagg catgaaaaaa 1380

ctaggtgttg gtgaagatat accaagtgat tatccatttt ataatgctca aatttcaaac 1440

aaaaatttag ataatgaaat attattagct gattcaggtt acggacaagg tgaaatactg 1500

attaacccag tacagatcct ttcaatctat agcgcattag aaaataatgg caatattaac 1560

gcacctcact tattaaaaga cacgaaaaac aaagtttgga agaaaaatat tatttccaaa 1620

gaaaatatca atctattaac tgatggtatg caacaagtcg taaataaaac acataaagaa 1680

gatatttata gatcttatgc aaacttaatt ggcaaatccg gtactgcaga actcaaaatg 1740

aaacaaggag aaactggcag acaaattggg tggtttatat catatgataa agataatcca 1800

aacatgatga tggctattaa tgttaaagat gtacaagata aaggaatggc tagctacaat 1860

gccaaaatct caggtaaagt gtatgatgag ctatatgaga acggtaataa aaaatacgat 1920

atagatgaat aa 1932

<210> 39

<211> 668

<212> PRT

<213> 金黄色葡萄球菌

<400> 39

Met Lys Lys Ile Lys Ile Val Pro Leu Ile Leu Ile Val Val Val Val

1 5 10 15

Gly Phe Gly Ile Tyr Phe Tyr Ala Ser Lys Asp Lys Glu Ile Asn Asn

20 25 30

Thr Ile Asp Ala Ile Glu Asp Lys Asn Phe Lys Gln Val Tyr Lys Asp

35 40 45

Ser Ser Tyr Ile Ser Lys Ser Asp Asn Gly Glu Val Glu Met Thr Glu

50 55 60

Arg Pro Ile Lys Ile Tyr Asn Ser Leu Gly Val Lys Asp Ile Asn Ile

65 70 75 80

Gln Asp Arg Lys Ile Lys Lys Val Ser Lys Asn Lys Lys Arg Val Asp

85 90 95

Ala Gln Tyr Lys Ile Lys Thr Asn Tyr Gly Asn Ile Asp Arg Asn Val

100 105 110

Gln Phe Asn Phe Val Lys Glu Asp Gly Met Trp Lys Leu Asp Trp Asp

115 120 125

His Ser Val Ile Ile Pro Gly Met Gln Lys Asp Gln Ser Ile His Ile

130 135 140

Glu Asn Leu Lys Ser Glu Arg Gly Lys Ile Leu Asp Arg Asn Asn Val

145 150 155 160

Glu Leu Ala Asn Thr Gly Thr Ala Tyr Glu Ile Gly Ile Val Pro Lys

165 170 175

Asn Val Ser Lys Lys Asp Tyr Lys Ala Ile Ala Lys Glu Leu Ser Ile

180 185 190

Ser Glu Asp Tyr Ile Lys Gln Gln Met Asp Gln Asn Trp Val Gln Asp

195 200 205

Asp Thr Phe Val Pro Leu Lys Thr Val Lys Lys Met Asp Glu Tyr Leu

210 215 220

Ser Asp Phe Ala Lys Lys Phe His Leu Thr Thr Asn Glu Thr Glu Ser

225 230 235 240

Arg Asn Tyr Pro Leu Gly Lys Ala Thr Ser His Leu Leu Gly Tyr Val

245 250 255

Gly Pro Ile Asn Ser Glu Glu Leu Lys Gln Lys Glu Tyr Lys Gly Tyr

260 265 270

Lys Asp Asp Ala Val Ile Gly Lys Lys Gly Leu Glu Lys Leu Tyr Asp

275 280 285

Lys Lys Leu Gln His Glu Asp Gly Tyr Arg Val Thr Ile Val Asp Asp

290 295 300

Asn Ser Asn Thr Ile Ala His Thr Leu Ile Glu Lys Lys Lys Lys Asp

305 310 315 320

Gly Lys Asp Ile Gln Leu Thr Ile Asp Ala Lys Val Gln Lys Ser Ile

325 330 335

Tyr Asn Asn Met Lys Asn Asp Tyr Gly Ser Gly Thr Ala Ile His Pro

340 345 350

Gln Thr Gly Glu Leu Leu Ala Leu Val Ser Thr Pro Ser Tyr Asp Val

355 360 365

Tyr Pro Phe Met Tyr Gly Met Ser Asn Glu Glu Tyr Asn Lys Leu Thr

370 375 380

Glu Asp Lys Lys Glu Pro Leu Leu Asn Lys Phe Gln Ile Thr Thr Ser

385 390 395 400

Pro Gly Ser Thr Gln Lys Ile Leu Thr Ala Met Ile Gly Leu Asn Asn

405 410 415

Lys Thr Leu Asp Asp Lys Thr Ser Tyr Lys Ile Asp Gly Lys Gly Trp

420 425 430

Gln Lys Asp Lys Ser Trp Gly Gly Tyr Asn Val Thr Arg Tyr Glu Val

435 440 445

Val Asn Gly Asn Ile Asp Leu Lys Gln Ala Ile Glu Ser Ser Asp Asn

450 455 460

Ile Phe Phe Ala Arg Val Ala Leu Glu Leu Gly Ser Lys Lys Phe Glu

465 470 475 480

Lys Gly Met Lys Lys Leu Gly Val Gly Glu Asp Ile Pro Ser Asp Tyr

485 490 495

Pro Phe Tyr Asn Ala Gln Ile Ser Asn Lys Asn Leu Asp Asn Glu Ile

500 505 510

Leu Leu Ala Asp Ser Gly Tyr Gly Gln Gly Glu Ile Leu Ile Asn Pro

515 520 525

Val Gln Ile Leu Ser Ile Tyr Ser Ala Leu Glu Asn Asn Gly Asn Ile

530 535 540

Asn Ala Pro His Leu Leu Lys Asp Thr Lys Asn Lys Val Trp Lys Lys

545 550 555 560

Asn Ile Ile Ser Lys Glu Asn Ile Asn Leu Leu Thr Asp Gly Met Gln

565 570 575

Gln Val Val Asn Lys Thr His Lys Glu Asp Ile Tyr Arg Ser Tyr Ala

580 585 590

Asn Leu Ile Gly Lys Ser Gly Thr Ala Glu Leu Lys Met Lys Gln Gly

595 600 605

Glu Thr Gly Arg Gln Ile Gly Trp Phe Ile Ser Tyr Asp Lys Asp Asn

610 615 620

Pro Asn Met Met Met Ala Ile Asn Val Lys Asp Val Gln Asp Lys Gly

625 630 635 640

Met Ala Ser Tyr Asn Ala Lys Ile Ser Gly Lys Val Tyr Asp Glu Leu

645 650 655

Tyr Glu Asn Gly Asn Lys Lys Tyr Asp Ile Asp Glu

660 665

<210> 40

<211> 643

<212> PRT

<213> 人工序列

<220>

<223> Pbp2a -克隆的肽序列

<400> 40

Lys Asp Lys Glu Ile Asn Asn Thr Ile Asp Ala Ile Glu Asp Lys Asn

1 5 10 15

Phe Lys Gln Val Tyr Lys Asp Ser Ser Tyr Ile Ser Lys Ser Asp Asn

20 25 30

Gly Glu Val Glu Met Thr Glu Arg Pro Ile Lys Ile Tyr Asn Ser Leu

35 40 45

Gly Val Lys Asp Ile Asn Ile Gln Asp Arg Lys Ile Lys Lys Val Ser

50 55 60

Lys Asn Lys Lys Arg Val Asp Ala Gln Tyr Lys Ile Lys Thr Asn Tyr

65 70 75 80

Gly Asn Ile Asp Arg Asn Val Gln Phe Asn Phe Val Lys Glu Asp Gly

85 90 95

Met Trp Lys Leu Asp Trp Asp His Ser Val Ile Ile Pro Gly Met Gln

100 105 110

Lys Asp Gln Ser Ile His Ile Glu Asn Leu Lys Ser Glu Arg Gly Lys

115 120 125

Ile Leu Asp Arg Asn Asn Val Glu Leu Ala Asn Thr Gly Thr Ala Tyr

130 135 140

Glu Ile Gly Ile Val Pro Lys Asn Val Ser Lys Lys Asp Tyr Lys Ala

145 150 155 160

Ile Ala Lys Glu Leu Ser Ile Ser Glu Asp Tyr Ile Lys Gln Gln Met

165 170 175

Asp Gln Asn Trp Val Gln Asp Asp Thr Phe Val Pro Leu Lys Thr Val

180 185 190

Lys Lys Met Asp Glu Tyr Leu Ser Asp Phe Ala Lys Lys Phe His Leu

195 200 205

Thr Thr Asn Glu Thr Glu Ser Arg Asn Tyr Pro Leu Gly Lys Ala Thr

210 215 220

Ser His Leu Leu Gly Tyr Val Gly Pro Ile Asn Ser Glu Glu Leu Lys

225 230 235 240

Gln Lys Glu Tyr Lys Gly Tyr Lys Asp Asp Ala Val Ile Gly Lys Lys

245 250 255

Gly Leu Glu Lys Leu Tyr Asp Lys Lys Leu Gln His Glu Asp Gly Tyr

260 265 270

Arg Val Thr Ile Val Asp Asp Asn Ser Asn Thr Ile Ala His Thr Leu

275 280 285

Ile Glu Lys Lys Lys Lys Asp Gly Lys Asp Ile Gln Leu Thr Ile Asp

290 295 300

Ala Lys Val Gln Lys Ser Ile Tyr Asn Asn Met Lys Asn Asp Tyr Gly

305 310 315 320

Ser Gly Thr Ala Ile His Pro Gln Thr Gly Glu Leu Leu Ala Leu Val

325 330 335

Ser Thr Pro Ser Tyr Asp Val Tyr Pro Phe Met Tyr Gly Met Ser Asn

340 345 350

Glu Glu Tyr Asn Lys Leu Thr Glu Asp Lys Lys Glu Pro Leu Leu Asn

355 360 365

Lys Phe Gln Ile Thr Thr Ser Pro Gly Ser Thr Gln Lys Ile Leu Thr

370 375 380

Ala Met Ile Gly Leu Asn Asn Lys Thr Leu Asp Asp Lys Thr Ser Tyr

385 390 395 400

Lys Ile Asp Gly Lys Gly Trp Gln Lys Asp Lys Ser Trp Gly Gly Tyr

405 410 415

Asn Val Thr Arg Tyr Glu Val Val Asn Gly Asn Ile Asp Leu Lys Gln

420 425 430

Ala Ile Glu Ser Ser Asp Asn Ile Phe Phe Ala Arg Val Ala Leu Glu

435 440 445

Leu Gly Ser Lys Lys Phe Glu Lys Gly Met Lys Lys Leu Gly Val Gly

450 455 460

Glu Asp Ile Pro Ser Asp Tyr Pro Phe Tyr Asn Ala Gln Ile Ser Asn

465 470 475 480

Lys Asn Leu Asp Asn Glu Ile Leu Leu Ala Asp Ser Gly Tyr Gly Gln

485 490 495

Gly Glu Ile Leu Ile Asn Pro Val Gln Ile Leu Ser Ile Tyr Ser Ala

500 505 510

Leu Glu Asn Asn Gly Asn Ile Asn Ala Pro His Leu Leu Lys Asp Thr

515 520 525

Lys Asn Lys Val Trp Lys Lys Asn Ile Ile Ser Lys Glu Asn Ile Asn

530 535 540

Leu Leu Thr Asp Gly Met Gln Gln Val Val Asn Lys Thr His Lys Glu

545 550 555 560

Asp Ile Tyr Arg Ser Tyr Ala Asn Leu Ile Gly Lys Ser Gly Thr Ala

565 570 575

Glu Leu Lys Met Lys Gln Gly Glu Thr Gly Arg Gln Ile Gly Trp Phe

580 585 590

Ile Ser Tyr Asp Lys Asp Asn Pro Asn Met Met Met Ala Ile Asn Val

595 600 605

Lys Asp Val Gln Asp Lys Gly Met Ala Ser Tyr Asn Ala Lys Ile Ser

610 615 620

Gly Lys Val Tyr Asp Glu Leu Tyr Glu Asn Gly Asn Lys Lys Tyr Asp

625 630 635 640

Ile Asp Glu

<210> 41

<211> 1029

<212> DNA

<213> 金黄色葡萄球菌

<400> 41

atgaaaggta aatttttaaa agttagttct ttattcgttg caactttgac aacagcgaca 60

cttgtgagtt ctccagcagc aaacgcgtta tcatcaaaag ctatggacaa tcatccacaa 120

caaacgcagt caagcaaaca gcaaacacct aagattaaaa aaggcggtaa ccttaaacca 180

ttagaacaac gtgaacacgc aaatgttata ttaccgaata acgatcgtca ccaaatcaca 240

gatacaacga atggtcatta tgcacccgta acttatattc aagttgaagc acctactggt 300

acatttattg cttccggtgt agttgtaggt aaagatactc ttttaacaaa taaacacgtc 360

gtagatgcta cgcacggtga tcctcatgct ttaaaagcat tcccttctgc aattaaccaa 420

gacaattatc caaatggtgg tttcactgct gaacaaatca ctaaatattc aggcgaaggt 480

gatttagcaa tagttaaatt ctcccctaat gagcaaaaca aacatattgg tgaagtagtt 540

aaaccagcaa caatgagtaa taatgctgaa acacaagtta accaaaatat tactgtaaca 600

ggatatcctg gtgataaacc tgtagcaaca atgtgggaaa gtaaaggaaa aatcacttac 660

ctcaaaggcg aagctatgca atatgattta agtacaactg gtggtaactc aggttcacct 720

gtatttaatg aaaaaaatga agtgatcgga attcattggg gcggtgtacc aaatgaattt 780

aatggtgcgg tatttattaa tgaaaatgta cgcaacttct taaaacaaaa tattgaagat 840

atccattttg ccaacgatga ccaacctaat aacccagata atcctgataa ccctaacaat 900

cctgataacc ctaacaatcc tgataaccct aacaacccag atgaaccaaa taaccctgac 960

aaccctaaca accctgataa tccagacaat ggcgataaca ataattcaga caaccctgac 1020

gctgcataa 1029

<210> 42

<211> 936

<212> DNA

<213> 人工序列

<220>

<223> SspA -克隆的DNA序列

<400> 42

tcatcaaaag ctatggacaa tcatccacaa caaacgcagt caagcaaaca gcaaacacct 60

aagattaaaa aaggcggtaa ccttaaacca ttagaacaac gtgaacacgc aaatgttata 120

ttaccgaata acgatcgtca ccaaatcaca gatacaacga atggtcatta tgcacccgta 180

acttatattc aagttgaagc acctactggt acatttattg cttccggtgt agttgtaggt 240

aaagatactc ttttaacaaa taaacacgtc gtagatgcta cgcacggtga tcctcatgct 300

ttaaaagcat tcccttctgc aattaaccaa gacaattatc caaatggtgg tttcactgct 360

gaacaaatca ctaaatattc aggcgaaggt gatttagcaa tagttaaatt ctcccctaat 420

gagcaaaaca aacatattgg tgaagtagtt aaaccagcaa caatgagtaa taatgctgaa 480

acacaagtta accaaaatat tactgtaaca ggatatcctg gtgataaacc tgtagcaaca 540

atgtgggaaa gtaaaggaaa aatcacttac ctcaaaggcg aagctatgca atatgattta 600

agtacaactg gtggtaactc aggttcacct gtatttaatg aaaaaaatga agtgatcgga 660

attcattggg gcggtgtacc aaatgaattt aatggtgcgg tatttattaa tgaaaatgta 720

cgcaacttct taaaacaaaa tattgaagat atccattttg ccaacgatga ccaacctaat 780

aacccagata atcctgataa ccctaacaat cctgataacc ctaacaatcc tgataaccct 840

aacaacccag atgaaccaaa taaccctgac aaccctaaca accctgataa tccagacaat 900

ggcgataaca ataattcaga caaccctgac gctgca 936

<210> 43

<211> 342

<212> PRT

<213> 金黄色葡萄球菌

<400> 43

Met Lys Gly Lys Phe Leu Lys Val Ser Ser Leu Phe Val Ala Thr Leu

1 5 10 15

Thr Thr Ala Thr Leu Val Ser Ser Pro Ala Ala Asn Ala Leu Ser Ser

20 25 30

Lys Ala Met Asp Asn His Pro Gln Gln Thr Gln Ser Ser Lys Gln Gln

35 40 45

Thr Pro Lys Ile Lys Lys Gly Gly Asn Leu Lys Pro Leu Glu Gln Arg

50 55 60

Glu His Ala Asn Val Ile Leu Pro Asn Asn Asp Arg His Gln Ile Thr

65 70 75 80

Asp Thr Thr Asn Gly His Tyr Ala Pro Val Thr Tyr Ile Gln Val Glu

85 90 95

Ala Pro Thr Gly Thr Phe Ile Ala Ser Gly Val Val Val Gly Lys Asp

100 105 110

Thr Leu Leu Thr Asn Lys His Val Val Asp Ala Thr His Gly Asp Pro

115 120 125

His Ala Leu Lys Ala Phe Pro Ser Ala Ile Asn Gln Asp Asn Tyr Pro

130 135 140

Asn Gly Gly Phe Thr Ala Glu Gln Ile Thr Lys Tyr Ser Gly Glu Gly

145 150 155 160

Asp Leu Ala Ile Val Lys Phe Ser Pro Asn Glu Gln Asn Lys His Ile

165 170 175

Gly Glu Val Val Lys Pro Ala Thr Met Ser Asn Asn Ala Glu Thr Gln

180 185 190

Val Asn Gln Asn Ile Thr Val Thr Gly Tyr Pro Gly Asp Lys Pro Val

195 200 205

Ala Thr Met Trp Glu Ser Lys Gly Lys Ile Thr Tyr Leu Lys Gly Glu

210 215 220

Ala Met Gln Tyr Asp Leu Ser Thr Thr Gly Gly Asn Ser Gly Ser Pro

225 230 235 240

Val Phe Asn Glu Lys Asn Glu Val Ile Gly Ile His Trp Gly Gly Val

245 250 255

Pro Asn Glu Phe Asn Gly Ala Val Phe Ile Asn Glu Asn Val Arg Asn

260 265 270

Phe Leu Lys Gln Asn Ile Glu Asp Ile His Phe Ala Asn Asp Asp Gln

275 280 285

Pro Asn Asn Pro Asp Asn Pro Asp Asn Pro Asn Asn Pro Asp Asn Pro

290 295 300

Asn Asn Pro Asp Asn Pro Asn Asn Pro Asp Glu Pro Asn Asn Pro Asp

305 310 315 320

Asn Pro Asn Asn Pro Asp Asn Pro Asp Asn Gly Asp Asn Asn Asn Ser

325 330 335

Asp Asn Pro Asp Ala Ala

340

<210> 44

<211> 312

<212> PRT

<213> 人工序列

<220>

<223> SspA -克隆的肽序列

<400> 44

Ser Ser Lys Ala Met Asp Asn His Pro Gln Gln Thr Gln Ser Ser Lys

1 5 10 15

Gln Gln Thr Pro Lys Ile Lys Lys Gly Gly Asn Leu Lys Pro Leu Glu

20 25 30

Gln Arg Glu His Ala Asn Val Ile Leu Pro Asn Asn Asp Arg His Gln

35 40 45

Ile Thr Asp Thr Thr Asn Gly His Tyr Ala Pro Val Thr Tyr Ile Gln

50 55 60

Val Glu Ala Pro Thr Gly Thr Phe Ile Ala Ser Gly Val Val Val Gly

65 70 75 80

Lys Asp Thr Leu Leu Thr Asn Lys His Val Val Asp Ala Thr His Gly

85 90 95

Asp Pro His Ala Leu Lys Ala Phe Pro Ser Ala Ile Asn Gln Asp Asn

100 105 110

Tyr Pro Asn Gly Gly Phe Thr Ala Glu Gln Ile Thr Lys Tyr Ser Gly

115 120 125

Glu Gly Asp Leu Ala Ile Val Lys Phe Ser Pro Asn Glu Gln Asn Lys

130 135 140

His Ile Gly Glu Val Val Lys Pro Ala Thr Met Ser Asn Asn Ala Glu

145 150 155 160

Thr Gln Val Asn Gln Asn Ile Thr Val Thr Gly Tyr Pro Gly Asp Lys

165 170 175

Pro Val Ala Thr Met Trp Glu Ser Lys Gly Lys Ile Thr Tyr Leu Lys

180 185 190

Gly Glu Ala Met Gln Tyr Asp Leu Ser Thr Thr Gly Gly Asn Ser Gly

195 200 205

Ser Pro Val Phe Asn Glu Lys Asn Glu Val Ile Gly Ile His Trp Gly

210 215 220

Gly Val Pro Asn Glu Phe Asn Gly Ala Val Phe Ile Asn Glu Asn Val

225 230 235 240

Arg Asn Phe Leu Lys Gln Asn Ile Glu Asp Ile His Phe Ala Asn Asp

245 250 255

Asp Gln Pro Asn Asn Pro Asp Asn Pro Asp Asn Pro Asn Asn Pro Asp

260 265 270

Asn Pro Asn Asn Pro Asp Asn Pro Asn Asn Pro Asp Glu Pro Asn Asn

275 280 285

Pro Asp Asn Pro Asn Asn Pro Asp Asn Pro Asp Asn Gly Asp Asn Asn

290 295 300

Asn Ser Asp Asn Pro Asp Ala Ala

305 310

<210> 45

<211> 492

<212> DNA

<213> 金黄色葡萄球菌

<400> 45

atgctcaaaa gaagtttatt atttttaact gttttattgt tattattctc attttcttca 60

attactaatg aggtaagtgc atcaagttca ttcgacaaag gaaaatataa aaaaggcgat 120

gacgcgagtt attttgaacc aacaggcccg tatttgatgg taaatgtgac tggagttgat 180

ggtaaaggaa atgaattgct atcccctcat tatgtcgagt ttcctattaa acctgggact 240

acacttacaa aagaaaaaat tgaatactat gtcgaatggg cattagatgc gacagcatat 300

aaagagttta gagtagttga attagatcca agcgcaaaga tcgaagtcac ttattatgat 360

aagaataaga aaaaagaaga aacgaagtct ttccctataa cagaaaaagg ttttgttgtc 420

ccagatttat cagagcatat taaaaaccct ggattcaact taattacaaa ggttgttata 480

gaaaagaaat aa 492

<210> 46

<211> 408

<212> DNA

<213> 人工序列

<220>

<223> Sak -克隆的DNA序列

<400> 46

agttcattcg acaaaggaaa atataaaaaa ggcgatgacg cgagttattt tgaaccaaca 60

ggcccgtatt tgatggtaaa tgtgactgga gttgatggta aaggaaatga attgctatcc 120

cctcattatg tcgagtttcc tattaaacct gggactacac ttacaaaaga aaaaattgaa 180

tactatgtcg aatgggcatt agatgcgaca gcatataaag agtttagagt agttgaatta 240

gatccaagcg caaagatcga agtcacttat tatgataaga ataagaaaaa agaagaaacg 300

aagtctttcc ctataacaga aaaaggtttt gttgtcccag atttatcaga gcatattaaa 360

aaccctggat tcaacttaat tacaaaggtt gttatagaaa agaaataa 408

<210> 47

<211> 163

<212> PRT

<213> 金黄色葡萄球菌

<400> 47

Met Leu Lys Arg Ser Leu Leu Phe Leu Thr Val Leu Leu Leu Leu Phe

1 5 10 15

Ser Phe Ser Ser Ile Thr Asn Glu Val Ser Ala Ser Ser Ser Phe Asp

20 25 30

Lys Gly Lys Tyr Lys Lys Gly Asp Asp Ala Ser Tyr Phe Glu Pro Thr

35 40 45

Gly Pro Tyr Leu Met Val Asn Val Thr Gly Val Asp Gly Lys Gly Asn

50 55 60

Glu Leu Leu Ser Pro His Tyr Val Glu Phe Pro Ile Lys Pro Gly Thr

65 70 75 80

Thr Leu Thr Lys Glu Lys Ile Glu Tyr Tyr Val Glu Trp Ala Leu Asp

85 90 95

Ala Thr Ala Tyr Lys Glu Phe Arg Val Val Glu Leu Asp Pro Ser Ala

100 105 110

Lys Ile Glu Val Thr Tyr Tyr Asp Lys Asn Lys Lys Lys Glu Glu Thr

115 120 125

Lys Ser Phe Pro Ile Thr Glu Lys Gly Phe Val Val Pro Asp Leu Ser

130 135 140

Glu His Ile Lys Asn Pro Gly Phe Asn Leu Ile Thr Lys Val Val Ile

145 150 155 160

Glu Lys Lys

<210> 48

<211> 135

<212> PRT

<213> 人工序列

<220>

<223> Sak -克隆的肽序列

<400> 48

Ser Ser Phe Asp Lys Gly Lys Tyr Lys Lys Gly Asp Asp Ala Ser Tyr

1 5 10 15

Phe Glu Pro Thr Gly Pro Tyr Leu Met Val Asn Val Thr Gly Val Asp

20 25 30

Gly Lys Gly Asn Glu Leu Leu Ser Pro His Tyr Val Glu Phe Pro Ile

35 40 45

Lys Pro Gly Thr Thr Leu Thr Lys Glu Lys Ile Glu Tyr Tyr Val Glu

50 55 60

Trp Ala Leu Asp Ala Thr Ala Tyr Lys Glu Phe Arg Val Val Glu Leu

65 70 75 80

Asp Pro Ser Ala Lys Ile Glu Val Thr Tyr Tyr Asp Lys Asn Lys Lys

85 90 95

Lys Glu Glu Thr Lys Ser Phe Pro Ile Thr Glu Lys Gly Phe Val Val

100 105 110

Pro Asp Leu Ser Glu His Ile Lys Asn Pro Gly Phe Asn Leu Ile Thr

115 120 125

Lys Val Val Ile Glu Lys Lys

130 135

<210> 49

<211> 702

<212> DNA

<213> 金黄色葡萄球菌

<400> 49

atgaaaaaga caattatggc atcatcatta gcagtggcat taggtgtaac aggttacgca 60

gcaggtacag gacatcaagc acacgctgct gaagtaaacg ttgatcaagc acacttagtt 120

gacttagcgc ataatcacca agatcaatta aatgcagctc caatcaaaga tggtgcatat 180

gacatccact ttgtaaaaga tggtttccaa tataacttta cttcaaatgg tactacatgg 240

tcatggagct atgaagcagc taatggtcaa actgctggtt tctcaaacgt tgcaggtgca 300

gactacacta cttcatacaa ccaaggttca gatgtacaat cagtaagcta caatgcacaa 360

tcaagtaact caaacgttga agctgtttca gctccaactt accataacta cagcacttca 420

actacttcaa gttcagtgag attaagcaat ggtaatactg caggtgctac tggttcatca 480

gcagctcaaa tcatggctca acgtactggt gtttcagctt ctacatgggc tgcaatcatc 540

gctcgtgaat caaatggtca agtaaatgct tacaacccat caggtgcttc aggtttattc 600

caaactatgc caggttgggg tccgacaaac actgttgacc aacaaatcaa cgcagctgtt 660

aaagcataca aagcacaagg tttaggtgct tggggattct aa 702

<210> 50

<211> 609

<212> DNA

<213> 人工序列

<220>

<223> IsaA -克隆的DNA序列

<400> 50

gtaaacgttg atcaagcaca cttagttgac ttagcgcata atcaccaaga tcaattaaat 60

gcagctccaa tcaaagatgg tgcatatgac atccactttg taaaagatgg tttccaatat 120

aactttactt caaatggtac tacatggtca tggagctatg aagcagctaa tggtcaaact 180

gctggtttct caaacgttgc aggtgcagac tacactactt catacaacca aggttcagat 240

gtacaatcag taagctacaa tgcacaatca agtaactcaa acgttgaagc tgtttcagct 300

ccaacttacc ataactacag cacttcaact acttcaagtt cagtgagatt aagcaatggt 360

aatactgcag gtgctactgg ttcatcagca gctcaaatca tggctcaacg tactggtgtt 420

tcagcttcta catgggctgc aatcatcgct cgtgaatcaa atggtcaagt aaatgcttac 480

aacccatcag gtgcttcagg tttattccaa actatgccag gttggggtcc gacaaacact 540

gttgaccaac aaatcaacgc agctgttaaa gcatacaaag cacaaggttt aggtgcttgg 600

ggattctaa 609

<210> 51

<211> 233

<212> PRT

<213> 金黄色葡萄球菌

<400> 51

Met Lys Lys Thr Ile Met Ala Ser Ser Leu Ala Val Ala Leu Gly Val

1 5 10 15

Thr Gly Tyr Ala Ala Gly Thr Gly His Gln Ala His Ala Ala Glu Val

20 25 30

Asn Val Asp Gln Ala His Leu Val Asp Leu Ala His Asn His Gln Asp

35 40 45

Gln Leu Asn Ala Ala Pro Ile Lys Asp Gly Ala Tyr Asp Ile His Phe

50 55 60

Val Lys Asp Gly Phe Gln Tyr Asn Phe Thr Ser Asn Gly Thr Thr Trp

65 70 75 80

Ser Trp Ser Tyr Glu Ala Ala Asn Gly Gln Thr Ala Gly Phe Ser Asn

85 90 95

Val Ala Gly Ala Asp Tyr Thr Thr Ser Tyr Asn Gln Gly Ser Asp Val

100 105 110

Gln Ser Val Ser Tyr Asn Ala Gln Ser Ser Asn Ser Asn Val Glu Ala

115 120 125

Val Ser Ala Pro Thr Tyr His Asn Tyr Ser Thr Ser Thr Thr Ser Ser

130 135 140

Ser Val Arg Leu Ser Asn Gly Asn Thr Ala Gly Ala Thr Gly Ser Ser

145 150 155 160

Ala Ala Gln Ile Met Ala Gln Arg Thr Gly Val Ser Ala Ser Thr Trp

165 170 175

Ala Ala Ile Ile Ala Arg Glu Ser Asn Gly Gln Val Asn Ala Tyr Asn

180 185 190

Pro Ser Gly Ala Ser Gly Leu Phe Gln Thr Met Pro Gly Trp Gly Pro

195 200 205

Thr Asn Thr Val Asp Gln Gln Ile Asn Ala Ala Val Lys Ala Tyr Lys

210 215 220

Ala Gln Gly Leu Gly Ala Trp Gly Phe

225 230

<210> 52

<211> 202

<212> PRT

<213> 人工序列

<220>

<223> IsaA -克隆的肽序列

<400> 52

Val Asn Val Asp Gln Ala His Leu Val Asp Leu Ala His Asn His Gln

1 5 10 15

Asp Gln Leu Asn Ala Ala Pro Ile Lys Asp Gly Ala Tyr Asp Ile His

20 25 30

Phe Val Lys Asp Gly Phe Gln Tyr Asn Phe Thr Ser Asn Gly Thr Thr

35 40 45

Trp Ser Trp Ser Tyr Glu Ala Ala Asn Gly Gln Thr Ala Gly Phe Ser

50 55 60

Asn Val Ala Gly Ala Asp Tyr Thr Thr Ser Tyr Asn Gln Gly Ser Asp

65 70 75 80

Val Gln Ser Val Ser Tyr Asn Ala Gln Ser Ser Asn Ser Asn Val Glu

85 90 95

Ala Val Ser Ala Pro Thr Tyr His Asn Tyr Ser Thr Ser Thr Thr Ser

100 105 110

Ser Ser Val Arg Leu Ser Asn Gly Asn Thr Ala Gly Ala Thr Gly Ser

115 120 125

Ser Ala Ala Gln Ile Met Ala Gln Arg Thr Gly Val Ser Ala Ser Thr

130 135 140

Trp Ala Ala Ile Ile Ala Arg Glu Ser Asn Gly Gln Val Asn Ala Tyr

145 150 155 160

Asn Pro Ser Gly Ala Ser Gly Leu Phe Gln Thr Met Pro Gly Trp Gly

165 170 175

Pro Thr Asn Thr Val Asp Gln Gln Ile Asn Ala Ala Val Lys Ala Tyr

180 185 190

Lys Ala Gln Gly Leu Gly Ala Trp Gly Phe

195 200

<210> 53

<211> 930

<212> DNA

<213> 金黄色葡萄球菌

<400> 53

atgactaact cttcgaaaag cttcactaaa tttatggctg cttctgctgt ttttactatg 60

ggatttttat cagtacctac tgctggcgct gaacaaacaa atcaaattgc aaataaacct 120

caggctattc aatggcatac aaatttaacg aatgagcgat tcactactat cgcacatcgt 180

ggcgcaagtg gctatgcacc agagcatacg tttcaagcat atgataagag tcataatgag 240

ttaaaagcat cttatatcga aattgattta caacgtacca aagatggaca tttagttgct 300

atgcatgatg aaactgttaa ccgtacaaca aatggacacg gtaaagttga ggattatacc 360

cttgatgaat taaaacagtt agatgcagga agttggttta ataaaaaata tccaaaatac 420

gcaagagcaa gttataaaaa tgctaaagta cccactttag atgaaatttt agaacgttat 480

ggcccgaatg caaactatta tattgaaaca aagtcacctg atgtataccc aggaatggaa 540

gaacaattat tagcttcatt gaaaaagcat caccttttaa ataacaataa attaaaaaat 600

ggacatgtaa tgattcaatc attttctgac gaaagtttaa agaaaattca tcgtcaaaat 660

aagcatgtgc cattagtaaa attagttgat aaaggtgaac tacaacaatt taacgaccaa 720

cgcttaaaag agatacgctc ttatgcgatt ggattaggtc ctgattatac agatttaact 780

gaacaaaata cccatcattt aaaagactta ggatttatag tacatcctta tacagtgaat 840

gaaaaagctg atatgttacg attaaataaa tatggcgttg atggtgtctt tacaaatttc 900

gctgataaat ataaagaagt cattaagtag 930

<210> 54

<211> 837

<212> DNA

<213> 人工序列

<220>

<223> GlpQ -克隆的DNA序列

<400> 54

caaacaaatc aaattgcaaa taaacctcag gctattcaat ggcatacaaa tttaacgaat 60

gagcgattca ctactatcgc acatcgtggc gcaagtggct atgcaccaga gcatacgttt 120

caagcatatg ataagagtca taatgagtta aaagcatctt atatcgaaat tgatttacaa 180

cgtaccaaag atggacattt agttgctatg catgatgaaa ctgttaaccg tacaacaaat 240

ggacacggta aagttgagga ttataccctt gatgaattaa aacagttaga tgcaggaagt 300

tggtttaata aaaaatatcc aaaatacgca agagcaagtt ataaaaatgc taaagtaccc 360

actttagatg aaattttaga acgttatggc ccgaatgcaa actattatat tgaaacaaag 420

tcacctgatg tatacccagg aatggaagaa caattattag cttcattgaa aaagcatcac 480

cttttaaata acaataaatt aaaaaatgga catgtaatga ttcaatcatt ttctgacgaa 540

agtttaaaga aaattcatcg tcaaaataag catgtgccat tagtaaaatt agttgataaa 600

ggtgaactac aacaatttaa cgaccaacgc ttaaaagaga tacgctctta tgcgattgga 660

ttaggtcctg attatacaga tttaactgaa caaaataccc atcatttaaa agacttagga 720

tttatagtac atccttatac agtgaatgaa aaagctgata tgttacgatt aaataaatat 780

ggcgttgatg gtgtctttac aaatttcgct gataaatata aagaagtcat taagtag 837

<210> 55

<211> 309

<212> PRT

<213> 金黄色葡萄球菌

<400> 55

Met Thr Asn Ser Ser Lys Ser Phe Thr Lys Phe Met Ala Ala Ser Ala

1 5 10 15

Val Phe Thr Met Gly Phe Leu Ser Val Pro Thr Ala Gly Ala Glu Gln

20 25 30

Thr Asn Gln Ile Ala Asn Lys Pro Gln Ala Ile Gln Trp His Thr Asn

35 40 45

Leu Thr Asn Glu Arg Phe Thr Thr Ile Ala His Arg Gly Ala Ser Gly

50 55 60

Tyr Ala Pro Glu His Thr Phe Gln Ala Tyr Asp Lys Ser His Asn Glu

65 70 75 80

Leu Lys Ala Ser Tyr Ile Glu Ile Asp Leu Gln Arg Thr Lys Asp Gly

85 90 95

His Leu Val Ala Met His Asp Glu Thr Val Asn Arg Thr Thr Asn Gly

100 105 110

His Gly Lys Val Glu Asp Tyr Thr Leu Asp Glu Leu Lys Gln Leu Asp

115 120 125

Ala Gly Ser Trp Phe Asn Lys Lys Tyr Pro Lys Tyr Ala Arg Ala Ser

130 135 140

Tyr Lys Asn Ala Lys Val Pro Thr Leu Asp Glu Ile Leu Glu Arg Tyr

145 150 155 160

Gly Pro Asn Ala Asn Tyr Tyr Ile Glu Thr Lys Ser Pro Asp Val Tyr

165 170 175

Pro Gly Met Glu Glu Gln Leu Leu Ala Ser Leu Lys Lys His His Leu

180 185 190

Leu Asn Asn Asn Lys Leu Lys Asn Gly His Val Met Ile Gln Ser Phe

195 200 205

Ser Asp Glu Ser Leu Lys Lys Ile His Arg Gln Asn Lys His Val Pro

210 215 220

Leu Val Lys Leu Val Asp Lys Gly Glu Leu Gln Gln Phe Asn Asp Gln

225 230 235 240

Arg Leu Lys Glu Ile Arg Ser Tyr Ala Ile Gly Leu Gly Pro Asp Tyr

245 250 255

Thr Asp Leu Thr Glu Gln Asn Thr His His Leu Lys Asp Leu Gly Phe

260 265 270

Ile Val His Pro Tyr Thr Val Asn Glu Lys Ala Asp Met Leu Arg Leu

275 280 285

Asn Lys Tyr Gly Val Asp Gly Val Phe Thr Asn Phe Ala Asp Lys Tyr

290 295 300

Lys Glu Val Ile Lys

305

<210> 56

<211> 278

<212> PRT

<213> 人工序列

<220>

<223> GlpQ -克隆的肽序列

<400> 56

Gln Thr Asn Gln Ile Ala Asn Lys Pro Gln Ala Ile Gln Trp His Thr

1 5 10 15

Asn Leu Thr Asn Glu Arg Phe Thr Thr Ile Ala His Arg Gly Ala Ser

20 25 30

Gly Tyr Ala Pro Glu His Thr Phe Gln Ala Tyr Asp Lys Ser His Asn

35 40 45

Glu Leu Lys Ala Ser Tyr Ile Glu Ile Asp Leu Gln Arg Thr Lys Asp

50 55 60

Gly His Leu Val Ala Met His Asp Glu Thr Val Asn Arg Thr Thr Asn

65 70 75 80

Gly His Gly Lys Val Glu Asp Tyr Thr Leu Asp Glu Leu Lys Gln Leu

85 90 95

Asp Ala Gly Ser Trp Phe Asn Lys Lys Tyr Pro Lys Tyr Ala Arg Ala

100 105 110

Ser Tyr Lys Asn Ala Lys Val Pro Thr Leu Asp Glu Ile Leu Glu Arg

115 120 125

Tyr Gly Pro Asn Ala Asn Tyr Tyr Ile Glu Thr Lys Ser Pro Asp Val

130 135 140

Tyr Pro Gly Met Glu Glu Gln Leu Leu Ala Ser Leu Lys Lys His His

145 150 155 160

Leu Leu Asn Asn Asn Lys Leu Lys Asn Gly His Val Met Ile Gln Ser

165 170 175

Phe Ser Asp Glu Ser Leu Lys Lys Ile His Arg Gln Asn Lys His Val

180 185 190

Pro Leu Val Lys Leu Val Asp Lys Gly Glu Leu Gln Gln Phe Asn Asp

195 200 205

Gln Arg Leu Lys Glu Ile Arg Ser Tyr Ala Ile Gly Leu Gly Pro Asp

210 215 220

Tyr Thr Asp Leu Thr Glu Gln Asn Thr His His Leu Lys Asp Leu Gly

225 230 235 240

Phe Ile Val His Pro Tyr Thr Val Asn Glu Lys Ala Asp Met Leu Arg

245 250 255

Leu Asn Lys Tyr Gly Val Asp Gly Val Phe Thr Asn Phe Ala Asp Lys

260 265 270

Tyr Lys Glu Val Ile Lys

275

<210> 57

<211> 1860

<212> DNA

<213> 金黄色葡萄球菌

<400> 57

atgcctaaaa ataaaatttt aatttatttg ctatcaacta cgctcgtatt acctacttta 60

gtttcaccta ccgcttatgc tgatacacct caaaaagata ctacagctaa gacaacatct 120

catgattcaa aaaaatctaa tgacgatgaa acttctaagg atactacaag taaagatact 180

gataaagcag acaacaataa tacaagtaac caagacaata acgacaaaaa atttaaaact 240

atagacgaca gcacttcaga ctctaacaat atcattgatt ttatttataa gaatttacca 300

caaaccaata taaaccaatt gctaaccaaa aataaatacg atgataatta ctcattaaca 360

actttaatcc aaaacttatt caatttaaat tcggatattt ctgattacga acaacctcgt 420

aatggcgaaa agtcaacaaa tgattcgaat aaaaacagtg acaatagcat caaaaatgac 480

actgatacgc aatcatctaa acaagataaa gcagacaatc aaaaagcacc taaatcaaac 540

aatacaaaac caagtacatc taataagcaa ccaaattcgc caaagccaac acaacctaat 600

caatcaaata gtcaaccagc aagtgacgat aaagcaaatc aaaaatcttc atcgaaagat 660

aatcaatcaa tgtcagattc ggctttagac tctattttgg atcaatacag tgaagatgca 720

aagaaaacac aaaaagatta tgcatctcaa tctaaaaaag acaaaaatga aaaatctaat 780

acaaagaatc cacagttacc aacacaagat gaattgaaac ataaatctaa acctgctcaa 840

tcattcaata acgatgttaa tcaaaaggat acacgtgcaa catcattatt cgaaacagat 900

cctagtatat ctaacaatga tgatagcgga caatttaacg ttgttgactc aaaagataca 960

cgtcaatttg tcaaatcaat tgctaaagat gcacatcgca ttggtcaaga taacgatatt 1020

tatgcgtctg tcatgattgc ccaagcaatc ttagaatctg actcaggtcg tagtgcttta 1080

gctaagtcac caaaccataa tttattcggt atcaaaggtg cttttgaagg gaattctgtt 1140

ccttttaaca cattagaagc tgatggtaat aaattgtata gtattaatgc tggattccga 1200

aaatatccaa gcacgaaaga atcactaaaa gattactctg accttattaa aaatggtatt 1260

gatggcaatc gaacaattta taaaccaaca tggaaatcgg aagccgattc ttataaagat 1320

gcaacatcac acttatctaa aacatatgct acagatccaa actatgctaa gaaattaaac 1380

agtattatta aacactatca attaactcag tttgacgatg aacgcatgcc agatttagat 1440

aaatatgaac gttctatcaa ggattatgat gattcatcag atgaattcaa acctttccgc 1500

gaggtatctg atagtatgcc atatccacat ggccaatgta cttggtacgt atataaccgt 1560

atgaaacaat ttggtacatc tatctcaggt gatttaggtg atgcacataa ttggaataat 1620

cgagctcaat accgtgatta tcaagtaagt catacaccaa aacgtcatgc tgctgttgta 1680

tttgaggctg gacaatttgg tgcagatcaa cattacggtc atgtagcatt tgttgaaaaa 1740

gttaacagtg atggttctat cgttatttca gaatccaatg ttaaaggatt aggtatcatt 1800

tctcatagaa ctatcaatgc agctgccgct gaagaattat catatattac aggtaaataa 1860

<210> 58

<211> 1776

<212> DNA

<213> 人工序列

<220>

<223> 自溶素样？克隆的DNA序列

<400> 58

acacctcaaa aagatactac agctaagaca acatctcatg attcaaaaaa atctaatgac 60

gatgaaactt ctaaggatac tacaagtaaa gatactgata aagcagacaa caataataca 120

agtaaccaag acaataacga caaaaaattt aaaactatag acgacagcac ttcagactct 180

aacaatatca ttgattttat ttataagaat ttaccacaaa ccaatataaa ccaattgcta 240

accaaaaata aatacgatga taattactca ttaacaactt taatccaaaa cttattcaat 300

ttaaattcgg atatttctga ttacgaacaa cctcgtaatg gcgaaaagtc aacaaatgat 360

tcgaataaaa acagtgacaa tagcatcaaa aatgacactg atacgcaatc atctaaacaa 420

gataaagcag acaatcaaaa agcacctaaa tcaaacaata caaaaccaag tacatctaat 480

aagcaaccaa attcgccaaa gccaacacaa cctaatcaat caaatagtca accagcaagt 540

gacgataaag caaatcaaaa atcttcatcg aaagataatc aatcaatgtc agattcggct 600

ttagactcta ttttggatca atacagtgaa gatgcaaaga aaacacaaaa agattatgca 660

tctcaatcta aaaaagacaa aaatgaaaaa tctaatacaa agaatccaca gttaccaaca 720

caagatgaat tgaaacataa atctaaacct gctcaatcat tcaataacga tgttaatcaa 780

aaggatacac gtgcaacatc attattcgaa acagatccta gtatatctaa caatgatgat 840

agcggacaat ttaacgttgt tgactcaaaa gatacacgtc aatttgtcaa atcaattgct 900

aaagatgcac atcgcattgg tcaagataac gatatttatg cgtctgtcat gattgcccaa 960

gcaatcttag aatctgactc aggtcgtagt gctttagcta agtcaccaaa ccataattta 1020

ttcggtatca aaggtgcttt tgaagggaat tctgttcctt ttaacacatt agaagctgat 1080

ggtaataaat tgtatagtat taatgctgga ttccgaaaat atccaagcac gaaagaatca 1140

ctaaaagatt actctgacct tattaaaaat ggtattgatg gcaatcgaac aatttataaa 1200

ccaacatgga aatcggaagc cgattcttat aaagatgcaa catcacactt atctaaaaca 1260

tatgctacag atccaaacta tgctaagaaa ttaaacagta ttattaaaca ctatcaatta 1320

actcagtttg acgatgaacg catgccagat ttagataaat atgaacgttc tatcaaggat 1380

tatgatgatt catcagatga attcaaacct ttccgcgagg tatctgatag tatgccatat 1440

ccacatggcc aatgtacttg gtacgtatat aaccgtatga aacaatttgg tacatctatc 1500

tcaggtgatt taggtgatgc acataattgg aataatcgag ctcaataccg tgattatcaa 1560

gtaagtcata caccaaaacg tcatgctgct gttgtatttg aggctggaca atttggtgca 1620

gatcaacatt acggtcatgt agcatttgtt gaaaaagtta acagtgatgg ttctatcgtt 1680

atttcagaat ccaatgttaa aggattaggt atcatttctc atagaactat caatgcagct 1740

gccgctgaag aattatcata tattacaggt aaataa 1776

<210> 59

<211> 619

<212> PRT

<213> 金黄色葡萄球菌

<400> 59

Met Pro Lys Asn Lys Ile Leu Ile Tyr Leu Leu Ser Thr Thr Leu Val

1 5 10 15

Leu Pro Thr Leu Val Ser Pro Thr Ala Tyr Ala Asp Thr Pro Gln Lys

20 25 30

Asp Thr Thr Ala Lys Thr Thr Ser His Asp Ser Lys Lys Ser Asn Asp

35 40 45

Asp Glu Thr Ser Lys Asp Thr Thr Ser Lys Asp Thr Asp Lys Ala Asp

50 55 60

Asn Asn Asn Thr Ser Asn Gln Asp Asn Asn Asp Lys Lys Phe Lys Thr

65 70 75 80

Ile Asp Asp Ser Thr Ser Asp Ser Asn Asn Ile Ile Asp Phe Ile Tyr

85 90 95

Lys Asn Leu Pro Gln Thr Asn Ile Asn Gln Leu Leu Thr Lys Asn Lys

100 105 110

Tyr Asp Asp Asn Tyr Ser Leu Thr Thr Leu Ile Gln Asn Leu Phe Asn

115 120 125

Leu Asn Ser Asp Ile Ser Asp Tyr Glu Gln Pro Arg Asn Gly Glu Lys

130 135 140

Ser Thr Asn Asp Ser Asn Lys Asn Ser Asp Asn Ser Ile Lys Asn Asp

145 150 155 160

Thr Asp Thr Gln Ser Ser Lys Gln Asp Lys Ala Asp Asn Gln Lys Ala

165 170 175

Pro Lys Ser Asn Asn Thr Lys Pro Ser Thr Ser Asn Lys Gln Pro Asn

180 185 190

Ser Pro Lys Pro Thr Gln Pro Asn Gln Ser Asn Ser Gln Pro Ala Ser

195 200 205

Asp Asp Lys Ala Asn Gln Lys Ser Ser Ser Lys Asp Asn Gln Ser Met

210 215 220

Ser Asp Ser Ala Leu Asp Ser Ile Leu Asp Gln Tyr Ser Glu Asp Ala

225 230 235 240

Lys Lys Thr Gln Lys Asp Tyr Ala Ser Gln Ser Lys Lys Asp Lys Asn

245 250 255

Glu Lys Ser Asn Thr Lys Asn Pro Gln Leu Pro Thr Gln Asp Glu Leu

260 265 270

Lys His Lys Ser Lys Pro Ala Gln Ser Phe Asn Asn Asp Val Asn Gln

275 280 285

Lys Asp Thr Arg Ala Thr Ser Leu Phe Glu Thr Asp Pro Ser Ile Ser

290 295 300

Asn Asn Asp Asp Ser Gly Gln Phe Asn Val Val Asp Ser Lys Asp Thr

305 310 315 320

Arg Gln Phe Val Lys Ser Ile Ala Lys Asp Ala His Arg Ile Gly Gln

325 330 335

Asp Asn Asp Ile Tyr Ala Ser Val Met Ile Ala Gln Ala Ile Leu Glu

340 345 350

Ser Asp Ser Gly Arg Ser Ala Leu Ala Lys Ser Pro Asn His Asn Leu

355 360 365

Phe Gly Ile Lys Gly Ala Phe Glu Gly Asn Ser Val Pro Phe Asn Thr

370 375 380

Leu Glu Ala Asp Gly Asn Lys Leu Tyr Ser Ile Asn Ala Gly Phe Arg

385 390 395 400

Lys Tyr Pro Ser Thr Lys Glu Ser Leu Lys Asp Tyr Ser Asp Leu Ile

405 410 415

Lys Asn Gly Ile Asp Gly Asn Arg Thr Ile Tyr Lys Pro Thr Trp Lys

420 425 430

Ser Glu Ala Asp Ser Tyr Lys Asp Ala Thr Ser His Leu Ser Lys Thr

435 440 445

Tyr Ala Thr Asp Pro Asn Tyr Ala Lys Lys Leu Asn Ser Ile Ile Lys

450 455 460

His Tyr Gln Leu Thr Gln Phe Asp Asp Glu Arg Met Pro Asp Leu Asp

465 470 475 480

Lys Tyr Glu Arg Ser Ile Lys Asp Tyr Asp Asp Ser Ser Asp Glu Phe

485 490 495

Lys Pro Phe Arg Glu Val Ser Asp Ser Met Pro Tyr Pro His Gly Gln

500 505 510

Cys Thr Trp Tyr Val Tyr Asn Arg Met Lys Gln Phe Gly Thr Ser Ile

515 520 525

Ser Gly Asp Leu Gly Asp Ala His Asn Trp Asn Asn Arg Ala Gln Tyr

530 535 540

Arg Asp Tyr Gln Val Ser His Thr Pro Lys Arg His Ala Ala Val Val

545 550 555 560

Phe Glu Ala Gly Gln Phe Gly Ala Asp Gln His Tyr Gly His Val Ala

565 570 575

Phe Val Glu Lys Val Asn Ser Asp Gly Ser Ile Val Ile Ser Glu Ser

580 585 590

Asn Val Lys Gly Leu Gly Ile Ile Ser His Arg Thr Ile Asn Ala Ala

595 600 605

Ala Ala Glu Glu Leu Ser Tyr Ile Thr Gly Lys

610 615

<210> 60

<211> 591

<212> PRT

<213> 人工序列

<220>

<223> 自溶素样? 克隆的肽序列

<400> 60

Thr Pro Gln Lys Asp Thr Thr Ala Lys Thr Thr Ser His Asp Ser Lys

1 5 10 15

Lys Ser Asn Asp Asp Glu Thr Ser Lys Asp Thr Thr Ser Lys Asp Thr

20 25 30

Asp Lys Ala Asp Asn Asn Asn Thr Ser Asn Gln Asp Asn Asn Asp Lys

35 40 45

Lys Phe Lys Thr Ile Asp Asp Ser Thr Ser Asp Ser Asn Asn Ile Ile

50 55 60

Asp Phe Ile Tyr Lys Asn Leu Pro Gln Thr Asn Ile Asn Gln Leu Leu

65 70 75 80

Thr Lys Asn Lys Tyr Asp Asp Asn Tyr Ser Leu Thr Thr Leu Ile Gln

85 90 95

Asn Leu Phe Asn Leu Asn Ser Asp Ile Ser Asp Tyr Glu Gln Pro Arg

100 105 110

Asn Gly Glu Lys Ser Thr Asn Asp Ser Asn Lys Asn Ser Asp Asn Ser

115 120 125

Ile Lys Asn Asp Thr Asp Thr Gln Ser Ser Lys Gln Asp Lys Ala Asp

130 135 140

Asn Gln Lys Ala Pro Lys Ser Asn Asn Thr Lys Pro Ser Thr Ser Asn

145 150 155 160

Lys Gln Pro Asn Ser Pro Lys Pro Thr Gln Pro Asn Gln Ser Asn Ser

165 170 175

Gln Pro Ala Ser Asp Asp Lys Ala Asn Gln Lys Ser Ser Ser Lys Asp

180 185 190

Asn Gln Ser Met Ser Asp Ser Ala Leu Asp Ser Ile Leu Asp Gln Tyr

195 200 205

Ser Glu Asp Ala Lys Lys Thr Gln Lys Asp Tyr Ala Ser Gln Ser Lys

210 215 220

Lys Asp Lys Asn Glu Lys Ser Asn Thr Lys Asn Pro Gln Leu Pro Thr

225 230 235 240

Gln Asp Glu Leu Lys His Lys Ser Lys Pro Ala Gln Ser Phe Asn Asn

245 250 255

Asp Val Asn Gln Lys Asp Thr Arg Ala Thr Ser Leu Phe Glu Thr Asp

260 265 270

Pro Ser Ile Ser Asn Asn Asp Asp Ser Gly Gln Phe Asn Val Val Asp

275 280 285

Ser Lys Asp Thr Arg Gln Phe Val Lys Ser Ile Ala Lys Asp Ala His

290 295 300

Arg Ile Gly Gln Asp Asn Asp Ile Tyr Ala Ser Val Met Ile Ala Gln

305 310 315 320

Ala Ile Leu Glu Ser Asp Ser Gly Arg Ser Ala Leu Ala Lys Ser Pro

325 330 335

Asn His Asn Leu Phe Gly Ile Lys Gly Ala Phe Glu Gly Asn Ser Val

340 345 350

Pro Phe Asn Thr Leu Glu Ala Asp Gly Asn Lys Leu Tyr Ser Ile Asn

355 360 365

Ala Gly Phe Arg Lys Tyr Pro Ser Thr Lys Glu Ser Leu Lys Asp Tyr

370 375 380

Ser Asp Leu Ile Lys Asn Gly Ile Asp Gly Asn Arg Thr Ile Tyr Lys

385 390 395 400

Pro Thr Trp Lys Ser Glu Ala Asp Ser Tyr Lys Asp Ala Thr Ser His

405 410 415

Leu Ser Lys Thr Tyr Ala Thr Asp Pro Asn Tyr Ala Lys Lys Leu Asn

420 425 430

Ser Ile Ile Lys His Tyr Gln Leu Thr Gln Phe Asp Asp Glu Arg Met

435 440 445

Pro Asp Leu Asp Lys Tyr Glu Arg Ser Ile Lys Asp Tyr Asp Asp Ser

450 455 460

Ser Asp Glu Phe Lys Pro Phe Arg Glu Val Ser Asp Ser Met Pro Tyr

465 470 475 480

Pro His Gly Gln Cys Thr Trp Tyr Val Tyr Asn Arg Met Lys Gln Phe

485 490 495

Gly Thr Ser Ile Ser Gly Asp Leu Gly Asp Ala His Asn Trp Asn Asn

500 505 510

Arg Ala Gln Tyr Arg Asp Tyr Gln Val Ser His Thr Pro Lys Arg His

515 520 525

Ala Ala Val Val Phe Glu Ala Gly Gln Phe Gly Ala Asp Gln His Tyr

530 535 540

Gly His Val Ala Phe Val Glu Lys Val Asn Ser Asp Gly Ser Ile Val

545 550 555 560

Ile Ser Glu Ser Asn Val Lys Gly Leu Gly Ile Ile Ser His Arg Thr

565 570 575

Ile Asn Ala Ala Ala Ala Glu Glu Leu Ser Tyr Ile Thr Gly Lys

580 585 590

<210> 61

<211> 960

<212> DNA

<213> 金黄色葡萄球菌

<400> 61

atgaaaacac gtatagtcag ctcagtaaca acaacactat tgctaggttc catattaatg 60

aatcctgtcg ctaatgccgc agattctgat attaatatta aaaccggtac tacagatatt 120

ggaagcaata ctacagtaaa aacaggtgat ttagtcactt atgataaaga aaatggcatg 180

cacaaaaaag tattttatag ttttatcgat gataaaaatc acaataaaaa actgctagtt 240

attagaacga aaggtaccat tgctggtcaa tatagagttt atagcgaaga aggtgctaac 300

aaaagtggtt tagcctggcc ttcagccttt aaggtacagt tgcaactacc tgataatgaa 360

gtagctcaaa tatctgatta ctatccaaga aattcgattg atacaaaaga gtatatgagt 420

actttaactt atggattcaa cggtaatgtt actggtgatg atacaggaaa aattggcggc 480

cttattggtg caaatgtttc gattggtcat acactgaaat atgttcaacc tgatttcaaa 540

acaattttag agagcccaac tgataaaaaa gtaggctgga aagtgatatt taacaatatg 600

gtgaatcaaa attggggacc atatgataga gattcttgga acccggtata tggcaatcaa 660

cttttcatga aaactagaaa tggttctatg aaagcagcag agaacttcct tgatcctaac 720

aaagcaagtt ctctattatc ttcagggttt tcaccagact tcgctacagt tattactatg 780

gatagaaaag catccaaaca acaaacaaat atagatgtaa tatacgaacg agttcgtgat 840

gactaccaat tgcattggac ttcaacaaat tggaaaggta ccaatactaa agataaatgg 900

acagatcgtt cttcagaaag atataaaatc gattgggaaa aagaagaaat gacaaattaa 960

<210> 62

<211> 882

<212> DNA

<213> 人工序列

<220>

<223> Hla -克隆的DNA序列

<400> 62

gcagattctg atattaatat taaaaccggt actacagata ttggaagcaa tactacagta 60

aaaacaggtg atttagtcac ttatgataaa gaaaatggca tgcacaaaaa agtattttat 120

agttttatcg atgataaaaa tcacaataaa aaactgctag ttattagaac gaaaggtacc 180

attgctggtc aatatagagt ttatagcgaa gaaggtgcta acaaaagtgg tttagcctgg 240

ccttcagcct ttaaggtaca gttgcaacta cctgataatg aagtagctca aatatctgat 300

tactatccaa gaaattcgat tgatacaaaa gagtatatga gtactttaac ttatggattc 360

aacggtaatg ttactggtga tgatacagga aaaattggcg gccttattgg tgcaaatgtt 420

tcgattggtc atacactgaa atatgttcaa cctgatttca aaacaatttt agagagccca 480

actgataaaa aagtaggctg gaaagtgata tttaacaata tggtgaatca aaattgggga 540

ccatatgata gagattcttg gaacccggta tatggcaatc aacttttcat gaaaactaga 600

aatggttcta tgaaagcagc agagaacttc cttgatccta acaaagcaag ttctctatta 660

tcttcagggt tttcaccaga cttcgctaca gttattacta tggatagaaa agcatccaaa 720

caacaaacaa atatagatgt aatatacgaa cgagttcgtg atgactacca attgcattgg 780

acttcaacaa attggaaagg taccaatact aaagataaat ggacagatcg ttcttcagaa 840

agatataaaa tcgattggga aaaagaagaa atgacaaatt aa 882

<210> 63

<211> 319

<212> PRT

<213> 金黄色葡萄球菌

<400> 63

Met Lys Thr Arg Ile Val Ser Ser Val Thr Thr Thr Leu Leu Leu Gly

1 5 10 15

Ser Ile Leu Met Asn Pro Val Ala Asn Ala Ala Asp Ser Asp Ile Asn

20 25 30

Ile Lys Thr Gly Thr Thr Asp Ile Gly Ser Asn Thr Thr Val Lys Thr

35 40 45

Gly Asp Leu Val Thr Tyr Asp Lys Glu Asn Gly Met His Lys Lys Val

50 55 60

Phe Tyr Ser Phe Ile Asp Asp Lys Asn His Asn Lys Lys Leu Leu Val

65 70 75 80

Ile Arg Thr Lys Gly Thr Ile Ala Gly Gln Tyr Arg Val Tyr Ser Glu

85 90 95

Glu Gly Ala Asn Lys Ser Gly Leu Ala Trp Pro Ser Ala Phe Lys Val

100 105 110

Gln Leu Gln Leu Pro Asp Asn Glu Val Ala Gln Ile Ser Asp Tyr Tyr

115 120 125

Pro Arg Asn Ser Ile Asp Thr Lys Glu Tyr Met Ser Thr Leu Thr Tyr

130 135 140

Gly Phe Asn Gly Asn Val Thr Gly Asp Asp Thr Gly Lys Ile Gly Gly

145 150 155 160

Leu Ile Gly Ala Asn Val Ser Ile Gly His Thr Leu Lys Tyr Val Gln

165 170 175

Pro Asp Phe Lys Thr Ile Leu Glu Ser Pro Thr Asp Lys Lys Val Gly

180 185 190

Trp Lys Val Ile Phe Asn Asn Met Val Asn Gln Asn Trp Gly Pro Tyr

195 200 205

Asp Arg Asp Ser Trp Asn Pro Val Tyr Gly Asn Gln Leu Phe Met Lys

210 215 220

Thr Arg Asn Gly Ser Met Lys Ala Ala Glu Asn Phe Leu Asp Pro Asn

225 230 235 240

Lys Ala Ser Ser Leu Leu Ser Ser Gly Phe Ser Pro Asp Phe Ala Thr

245 250 255

Val Ile Thr Met Asp Arg Lys Ala Ser Lys Gln Gln Thr Asn Ile Asp

260 265 270

Val Ile Tyr Glu Arg Val Arg Asp Asp Tyr Gln Leu His Trp Thr Ser

275 280 285

Thr Asn Trp Lys Gly Thr Asn Thr Lys Asp Lys Trp Thr Asp Arg Ser

290 295 300

Ser Glu Arg Tyr Lys Ile Asp Trp Glu Lys Glu Glu Met Thr Asn

305 310 315

<210> 64

<211> 293

<212> PRT

<213> 人工序列

<220>

<223> Hla -克隆的肽序列

<400> 64

Ala Asp Ser Asp Ile Asn Ile Lys Thr Gly Thr Thr Asp Ile Gly Ser

1 5 10 15

Asn Thr Thr Val Lys Thr Gly Asp Leu Val Thr Tyr Asp Lys Glu Asn

20 25 30

Gly Met His Lys Lys Val Phe Tyr Ser Phe Ile Asp Asp Lys Asn His

35 40 45

Asn Lys Lys Leu Leu Val Ile Arg Thr Lys Gly Thr Ile Ala Gly Gln

50 55 60

Tyr Arg Val Tyr Ser Glu Glu Gly Ala Asn Lys Ser Gly Leu Ala Trp

65 70 75 80

Pro Ser Ala Phe Lys Val Gln Leu Gln Leu Pro Asp Asn Glu Val Ala

85 90 95

Gln Ile Ser Asp Tyr Tyr Pro Arg Asn Ser Ile Asp Thr Lys Glu Tyr

100 105 110

Met Ser Thr Leu Thr Tyr Gly Phe Asn Gly Asn Val Thr Gly Asp Asp

115 120 125

Thr Gly Lys Ile Gly Gly Leu Ile Gly Ala Asn Val Ser Ile Gly His

130 135 140

Thr Leu Lys Tyr Val Gln Pro Asp Phe Lys Thr Ile Leu Glu Ser Pro

145 150 155 160

Thr Asp Lys Lys Val Gly Trp Lys Val Ile Phe Asn Asn Met Val Asn

165 170 175

Gln Asn Trp Gly Pro Tyr Asp Arg Asp Ser Trp Asn Pro Val Tyr Gly

180 185 190

Asn Gln Leu Phe Met Lys Thr Arg Asn Gly Ser Met Lys Ala Ala Glu

195 200 205

Asn Phe Leu Asp Pro Asn Lys Ala Ser Ser Leu Leu Ser Ser Gly Phe

210 215 220

Ser Pro Asp Phe Ala Thr Val Ile Thr Met Asp Arg Lys Ala Ser Lys

225 230 235 240

Gln Gln Thr Asn Ile Asp Val Ile Tyr Glu Arg Val Arg Asp Asp Tyr

245 250 255

Gln Leu His Trp Thr Ser Thr Asn Trp Lys Gly Thr Asn Thr Lys Asp

260 265 270

Lys Trp Thr Asp Arg Ser Ser Glu Arg Tyr Lys Ile Asp Trp Glu Lys

275 280 285

Glu Glu Met Thr Asn

290

<210> 65

<211> 1053

<212> DNA

<213> 金黄色葡萄球菌

<400> 65

atgacaaaac attatttaaa cagtaagtat caatcagaac aacgttcatc agctatgaaa 60

aagattacaa tgggtacagc atctatcatt ttaggttccc ttgtatacat aggcgcagac 120

agccaacaag tcaatgcggc aacagaagct acgaacgcaa ctaataatca aagcacacaa 180

gtttctcaag caacatcaca accaattaat ttccaagtgc aaaaagatgg ctcttcagag 240

aagtcacaca tggatgacta tatgcaacac cctggtaaag taattaaaca aaataataaa 300

tattatttcc aaaccgtgtt aaacaatgca tcattctgga aagaatacaa attttacaat 360

gcaaacaatc aagaattagc aacaactgtt gttaacgata ataaaaaagc ggatactaga 420

acaatcaatg ttgcagttga acctggatat aagagcttaa ctactaaagt acatattgtc 480

gtgccacaaa ttaattacaa tcatagatat actacgcatt tggaatttga aaaagcaatt 540

cctacattag ctgacgcagc aaaaccaaac aatgttaaac cggttcaacc aaaaccagct 600

caacctaaaa cacctactga gcaaactaaa ccagttcaac ctaaagttga aaaagttaaa 660

cctactgtaa ctacaacaag caaagttgaa gacaatcact ctactaaagt tgtaagtact 720

gacacaacaa aagatcaaac taaaacacaa actgctcata cagttaaaac agcacaaact 780

gctcaagaac aaaataaagt tcaaacacct gttaaagatg ttgcaacagc gaaatctgaa 840

agcaacaatc aagctgtaag tgataataaa tcacaacaaa ctaacaaagt tacaaaacat 900

aacgaaacgc ctaaacaagc atctaaagct aaagaattac caaaaactgg tttaacttca 960

gttgataact ttattagcac agttgccttc gcaacacttg cccttttagg ttcattatct 1020

ttattacttt tcaaaagaaa agaatctaaa taa 1053

<210> 66

<211> 915

<212> DNA

<213> 人工序列

<220>

<223> IsdA -克隆的DNA序列

<400> 66

gcaacagaag ctacgaacgc aactaataat caaagcacac aagtttctca agcaacatca 60

caaccaatta atttccaagt gcaaaaagat ggctcttcag agaagtcaca catggatgac 120

tatatgcaac accctggtaa agtaattaaa caaaataata aatattattt ccaaaccgtg 180

ttaaacaatg catcattctg gaaagaatac aaattttaca atgcaaacaa tcaagaatta 240

gcaacaactg ttgttaacga taataaaaaa gcggatacta gaacaatcaa tgttgcagtt 300

gaacctggat ataagagctt aactactaaa gtacatattg tcgtgccaca aattaattac 360

aatcatagat atactacgca tttggaattt gaaaaagcaa ttcctacatt agctgacgca 420

gcaaaaccaa acaatgttaa accggttcaa ccaaaaccag ctcaacctaa aacacctact 480

gagcaaacta aaccagttca acctaaagtt gaaaaagtta aacctactgt aactacaaca 540

agcaaagttg aagacaatca ctctactaaa gttgtaagta ctgacacaac aaaagatcaa 600

actaaaacac aaactgctca tacagttaaa acagcacaaa ctgctcaaga acaaaataaa 660

gttcaaacac ctgttaaaga tgttgcaaca gcgaaatctg aaagcaacaa tcaagctgta 720

agtgataata aatcacaaca aactaacaaa gttacaaaac ataacgaaac gcctaaacaa 780

gcatctaaag ctaaagaatt accaaaaact ggtttaactt cagttgataa ctttattagc 840

acagttgcct tcgcaacact tgccctttta ggttcattat ctttattact tttcaaaaga 900

aaagaatcta aataa 915

<210> 67

<211> 350

<212> PRT

<213> 金黄色葡萄球菌

<400> 67

Met Thr Lys His Tyr Leu Asn Ser Lys Tyr Gln Ser Glu Gln Arg Ser

1 5 10 15

Ser Ala Met Lys Lys Ile Thr Met Gly Thr Ala Ser Ile Ile Leu Gly

20 25 30

Ser Leu Val Tyr Ile Gly Ala Asp Ser Gln Gln Val Asn Ala Ala Thr

35 40 45

Glu Ala Thr Asn Ala Thr Asn Asn Gln Ser Thr Gln Val Ser Gln Ala

50 55 60

Thr Ser Gln Pro Ile Asn Phe Gln Val Gln Lys Asp Gly Ser Ser Glu

65 70 75 80

Lys Ser His Met Asp Asp Tyr Met Gln His Pro Gly Lys Val Ile Lys

85 90 95

Gln Asn Asn Lys Tyr Tyr Phe Gln Thr Val Leu Asn Asn Ala Ser Phe

100 105 110

Trp Lys Glu Tyr Lys Phe Tyr Asn Ala Asn Asn Gln Glu Leu Ala Thr

115 120 125

Thr Val Val Asn Asp Asn Lys Lys Ala Asp Thr Arg Thr Ile Asn Val

130 135 140

Ala Val Glu Pro Gly Tyr Lys Ser Leu Thr Thr Lys Val His Ile Val

145 150 155 160

Val Pro Gln Ile Asn Tyr Asn His Arg Tyr Thr Thr His Leu Glu Phe

165 170 175

Glu Lys Ala Ile Pro Thr Leu Ala Asp Ala Ala Lys Pro Asn Asn Val

180 185 190

Lys Pro Val Gln Pro Lys Pro Ala Gln Pro Lys Thr Pro Thr Glu Gln

195 200 205

Thr Lys Pro Val Gln Pro Lys Val Glu Lys Val Lys Pro Thr Val Thr

210 215 220

Thr Thr Ser Lys Val Glu Asp Asn His Ser Thr Lys Val Val Ser Thr

225 230 235 240

Asp Thr Thr Lys Asp Gln Thr Lys Thr Gln Thr Ala His Thr Val Lys

245 250 255

Thr Ala Gln Thr Ala Gln Glu Gln Asn Lys Val Gln Thr Pro Val Lys

260 265 270

Asp Val Ala Thr Ala Lys Ser Glu Ser Asn Asn Gln Ala Val Ser Asp

275 280 285

Asn Lys Ser Gln Gln Thr Asn Lys Val Thr Lys His Asn Glu Thr Pro

290 295 300

Lys Gln Ala Ser Lys Ala Lys Glu Leu Pro Lys Thr Gly Leu Thr Ser

305 310 315 320

Val Asp Asn Phe Ile Ser Thr Val Ala Phe Ala Thr Leu Ala Leu Leu

325 330 335

Gly Ser Leu Ser Leu Leu Leu Phe Lys Arg Lys Glu Ser Lys

340 345 350

<210> 68

<211> 304

<212> PRT

<213> 人工序列

<220>

<223> IsdA -克隆的肽序列

<400> 68

Ala Thr Glu Ala Thr Asn Ala Thr Asn Asn Gln Ser Thr Gln Val Ser

1 5 10 15

Gln Ala Thr Ser Gln Pro Ile Asn Phe Gln Val Gln Lys Asp Gly Ser

20 25 30

Ser Glu Lys Ser His Met Asp Asp Tyr Met Gln His Pro Gly Lys Val

35 40 45

Ile Lys Gln Asn Asn Lys Tyr Tyr Phe Gln Thr Val Leu Asn Asn Ala

50 55 60

Ser Phe Trp Lys Glu Tyr Lys Phe Tyr Asn Ala Asn Asn Gln Glu Leu

65 70 75 80

Ala Thr Thr Val Val Asn Asp Asn Lys Lys Ala Asp Thr Arg Thr Ile

85 90 95

Asn Val Ala Val Glu Pro Gly Tyr Lys Ser Leu Thr Thr Lys Val His

100 105 110

Ile Val Val Pro Gln Ile Asn Tyr Asn His Arg Tyr Thr Thr His Leu

115 120 125

Glu Phe Glu Lys Ala Ile Pro Thr Leu Ala Asp Ala Ala Lys Pro Asn

130 135 140

Asn Val Lys Pro Val Gln Pro Lys Pro Ala Gln Pro Lys Thr Pro Thr

145 150 155 160

Glu Gln Thr Lys Pro Val Gln Pro Lys Val Glu Lys Val Lys Pro Thr

165 170 175

Val Thr Thr Thr Ser Lys Val Glu Asp Asn His Ser Thr Lys Val Val

180 185 190

Ser Thr Asp Thr Thr Lys Asp Gln Thr Lys Thr Gln Thr Ala His Thr

195 200 205

Val Lys Thr Ala Gln Thr Ala Gln Glu Gln Asn Lys Val Gln Thr Pro

210 215 220

Val Lys Asp Val Ala Thr Ala Lys Ser Glu Ser Asn Asn Gln Ala Val

225 230 235 240

Ser Asp Asn Lys Ser Gln Gln Thr Asn Lys Val Thr Lys His Asn Glu

245 250 255

Thr Pro Lys Gln Ala Ser Lys Ala Lys Glu Leu Pro Lys Thr Gly Leu

260 265 270

Thr Ser Val Asp Asn Phe Ile Ser Thr Val Ala Phe Ala Thr Leu Ala

275 280 285

Leu Leu Gly Ser Leu Ser Leu Leu Leu Phe Lys Arg Lys Glu Ser Lys

290 295 300

<210> 69

<211> 1938

<212> DNA

<213> 金黄色葡萄球菌

<400> 69

atgaacaaac agcaaaaaga atttaaatca ttttattcaa ttagaaagtc atcactaggc 60

gttgcatctg tagcgattag tacactttta ttattaatgt caaatggcga agcacaagca 120

gcagctgaag aaacaggtgg tacaaataca gaagcacaac caaaaactga agcagttgca 180

agtccaacaa caacatctga aaaagctcca gaaactaaac cagtagctaa tgctgtctca 240

gtatctaata aagaagttga ggcccctact tctgaaacaa aagaagctaa agaagttaaa 300

gaagttaaag cccctaagga aacaaaagca gttaaaccag cagcaaaagc cactaacaat 360

acatatccta ttttgaatca ggaacttaga gaagcgatta aaaaccctgc aataaaagat 420

aaagatcata gcgcaccaaa ctctcgtcca attgattttg aaatgaaaaa agaaaatggt 480

gagcaacaat tttatcatta tgccagctct gttaaacctg ctagagttat tttcactgat 540

tcaaaaccag aaattgaatt aggattacaa tcaggtcaat tttggagaaa atttgaagtt 600

tatgaaggtg acaaaaagtt gccaattaaa ttagtatcat acgatactgt taaagattac 660

gcttacattc gcttctctgt ttcaaatgga acaaaagccg ttaaaattgt aagttcaact 720

cacttcaata acaaagaaga aaaatacgat tacacattaa tggaattcgc acaaccaatt 780

tataacagtg cagataaatt caaaactgaa gaagattata aagctgaaaa attattagcg 840

ccatataaaa aagcgaaaac actagaaaga caagtttatg aattaaataa aattcaagat 900

aaacttcctg aaaaattaaa ggctgagtac aagaagaaat tagaggatac aaagaaagct 960

ttagatgagc aagtgaaatc agctattact gaattccaaa atgtacaacc aacaaatgaa 1020

aaaatgactg atttacaaga tacaaaatat gttgtttatg aaagtgttga gaataacgaa 1080

tctatgatgg atacttttgt taaacaccct attaaaacag gtatgcttaa cggcaaaaaa 1140

tatatggtca tggaaactac taatgacgat tactggaaag atttcatggt tgaaggtcaa 1200

cgtgttagaa ctataagcaa agatgctaaa aataatacta gaacaattat tttcccatat 1260

gttgaaggta aaactctata tgatgctatc gttaaagttc acgtaaaaac gattgattat 1320

gatggacaat accatgtcag aatcgttgat aaagaagcat ttacaaaagc caataccgat 1380

aaatctaaca aaaaagaaca acaagataac tcagctaaga aggaagctac tccagctacg 1440

cctagcaaac caacaccatc acctgttgaa aaagaatcac aaaaacaaga cagccaaaaa 1500

gatgacaata aacaattacc aagtgttgaa aaagaaaatg acgcatctag tgagtcaggt 1560

aaagacaaaa cgcctgctac aaaaccaact aaaggtgaag tagaatcaag tagtacaact 1620

ccaactaagg tagtatctac gactcaaaat gttgcaaaac caacaactgc ttcatcaaaa 1680

acaacaaaag atgttgttca aacttcagca ggttctagcg aagcaaaaga tagtgctcca 1740

ttacaaaaag caaacattaa aaacacaaat gatggacaca ctcaaagcca aaacaataaa 1800

aatacacaag aaaataaagc aaaatcatta ccacaaactg gtgaagaatc aaataaagat 1860

atgacattac cattaatggc attactagct ttaagtagca tcgttgcatt cgtattacct 1920

agaaaacgta aaaactaa 1938

<210> 70

<211> 1818

<212> DNA

<213> 人工序列

<220>

<223> IsdB -克隆的DNA序列

<400> 70

gcagctgaag aaacaggtgg tacaaataca gaagcacaac caaaaactga agcagttgca 60

agtccaacaa caacatctga aaaagctcca gaaactaaac cagtagctaa tgctgtctca 120

gtatctaata aagaagttga ggcccctact tctgaaacaa aagaagctaa agaagttaaa 180

gaagttaaag cccctaagga aacaaaagca gttaaaccag cagcaaaagc cactaacaat 240

acatatccta ttttgaatca ggaacttaga gaagcgatta aaaaccctgc aataaaagat 300

aaagatcata gcgcaccaaa ctctcgtcca attgattttg aaatgaaaaa agaaaatggt 360

gagcaacaat tttatcatta tgccagctct gttaaacctg ctagagttat tttcactgat 420

tcaaaaccag aaattgaatt aggattacaa tcaggtcaat tttggagaaa atttgaagtt 480

tatgaaggtg acaaaaagtt gccaattaaa ttagtatcat acgatactgt taaagattac 540

gcttacattc gcttctctgt ttcaaatgga acaaaagccg ttaaaattgt aagttcaact 600

cacttcaata acaaagaaga aaaatacgat tacacattaa tggaattcgc acaaccaatt 660

tataacagtg cagataaatt caaaactgaa gaagattata aagctgaaaa attattagcg 720

ccatataaaa aagcgaaaac actagaaaga caagtttatg aattaaataa aattcaagat 780

aaacttcctg aaaaattaaa ggctgagtac aagaagaaat tagaggatac aaagaaagct 840

ttagatgagc aagtgaaatc agctattact gaattccaaa atgtacaacc aacaaatgaa 900

aaaatgactg atttacaaga tacaaaatat gttgtttatg aaagtgttga gaataacgaa 960

tctatgatgg atacttttgt taaacaccct attaaaacag gtatgcttaa cggcaaaaaa 1020

tatatggtca tggaaactac taatgacgat tactggaaag atttcatggt tgaaggtcaa 1080

cgtgttagaa ctataagcaa agatgctaaa aataatacta gaacaattat tttcccatat 1140

gttgaaggta aaactctata tgatgctatc gttaaagttc acgtaaaaac gattgattat 1200

gatggacaat accatgtcag aatcgttgat aaagaagcat ttacaaaagc caataccgat 1260

aaatctaaca aaaaagaaca acaagataac tcagctaaga aggaagctac tccagctacg 1320

cctagcaaac caacaccatc acctgttgaa aaagaatcac aaaaacaaga cagccaaaaa 1380

gatgacaata aacaattacc aagtgttgaa aaagaaaatg acgcatctag tgagtcaggt 1440

aaagacaaaa cgcctgctac aaaaccaact aaaggtgaag tagaatcaag tagtacaact 1500

ccaactaagg tagtatctac gactcaaaat gttgcaaaac caacaactgc ttcatcaaaa 1560

acaacaaaag atgttgttca aacttcagca ggttctagcg aagcaaaaga tagtgctcca 1620

ttacaaaaag caaacattaa aaacacaaat gatggacaca ctcaaagcca aaacaataaa 1680

aatacacaag aaaataaagc aaaatcatta ccacaaactg gtgaagaatc aaataaagat 1740

atgacattac cattaatggc attactagct ttaagtagca tcgttgcatt cgtattacct 1800

agaaaacgta aaaactaa 1818

<210> 71

<211> 645

<212> PRT

<213> 金黄色葡萄球菌

<400> 71

Met Asn Lys Gln Gln Lys Glu Phe Lys Ser Phe Tyr Ser Ile Arg Lys

1 5 10 15

Ser Ser Leu Gly Val Ala Ser Val Ala Ile Ser Thr Leu Leu Leu Leu

20 25 30

Met Ser Asn Gly Glu Ala Gln Ala Ala Ala Glu Glu Thr Gly Gly Thr

35 40 45

Asn Thr Glu Ala Gln Pro Lys Thr Glu Ala Val Ala Ser Pro Thr Thr

50 55 60

Thr Ser Glu Lys Ala Pro Glu Thr Lys Pro Val Ala Asn Ala Val Ser

65 70 75 80

Val Ser Asn Lys Glu Val Glu Ala Pro Thr Ser Glu Thr Lys Glu Ala

85 90 95

Lys Glu Val Lys Glu Val Lys Ala Pro Lys Glu Thr Lys Ala Val Lys

100 105 110

Pro Ala Ala Lys Ala Thr Asn Asn Thr Tyr Pro Ile Leu Asn Gln Glu

115 120 125

Leu Arg Glu Ala Ile Lys Asn Pro Ala Ile Lys Asp Lys Asp His Ser

130 135 140

Ala Pro Asn Ser Arg Pro Ile Asp Phe Glu Met Lys Lys Glu Asn Gly

145 150 155 160

Glu Gln Gln Phe Tyr His Tyr Ala Ser Ser Val Lys Pro Ala Arg Val

165 170 175

Ile Phe Thr Asp Ser Lys Pro Glu Ile Glu Leu Gly Leu Gln Ser Gly

180 185 190

Gln Phe Trp Arg Lys Phe Glu Val Tyr Glu Gly Asp Lys Lys Leu Pro

195 200 205

Ile Lys Leu Val Ser Tyr Asp Thr Val Lys Asp Tyr Ala Tyr Ile Arg

210 215 220

Phe Ser Val Ser Asn Gly Thr Lys Ala Val Lys Ile Val Ser Ser Thr

225 230 235 240

His Phe Asn Asn Lys Glu Glu Lys Tyr Asp Tyr Thr Leu Met Glu Phe

245 250 255

Ala Gln Pro Ile Tyr Asn Ser Ala Asp Lys Phe Lys Thr Glu Glu Asp

260 265 270

Tyr Lys Ala Glu Lys Leu Leu Ala Pro Tyr Lys Lys Ala Lys Thr Leu

275 280 285

Glu Arg Gln Val Tyr Glu Leu Asn Lys Ile Gln Asp Lys Leu Pro Glu

290 295 300

Lys Leu Lys Ala Glu Tyr Lys Lys Lys Leu Glu Asp Thr Lys Lys Ala

305 310 315 320

Leu Asp Glu Gln Val Lys Ser Ala Ile Thr Glu Phe Gln Asn Val Gln

325 330 335

Pro Thr Asn Glu Lys Met Thr Asp Leu Gln Asp Thr Lys Tyr Val Val

340 345 350

Tyr Glu Ser Val Glu Asn Asn Glu Ser Met Met Asp Thr Phe Val Lys

355 360 365

His Pro Ile Lys Thr Gly Met Leu Asn Gly Lys Lys Tyr Met Val Met

370 375 380

Glu Thr Thr Asn Asp Asp Tyr Trp Lys Asp Phe Met Val Glu Gly Gln

385 390 395 400

Arg Val Arg Thr Ile Ser Lys Asp Ala Lys Asn Asn Thr Arg Thr Ile

405 410 415

Ile Phe Pro Tyr Val Glu Gly Lys Thr Leu Tyr Asp Ala Ile Val Lys

420 425 430

Val His Val Lys Thr Ile Asp Tyr Asp Gly Gln Tyr His Val Arg Ile

435 440 445

Val Asp Lys Glu Ala Phe Thr Lys Ala Asn Thr Asp Lys Ser Asn Lys

450 455 460

Lys Glu Gln Gln Asp Asn Ser Ala Lys Lys Glu Ala Thr Pro Ala Thr

465 470 475 480

Pro Ser Lys Pro Thr Pro Ser Pro Val Glu Lys Glu Ser Gln Lys Gln

485 490 495

Asp Ser Gln Lys Asp Asp Asn Lys Gln Leu Pro Ser Val Glu Lys Glu

500 505 510

Asn Asp Ala Ser Ser Glu Ser Gly Lys Asp Lys Thr Pro Ala Thr Lys

515 520 525

Pro Thr Lys Gly Glu Val Glu Ser Ser Ser Thr Thr Pro Thr Lys Val

530 535 540

Val Ser Thr Thr Gln Asn Val Ala Lys Pro Thr Thr Ala Ser Ser Lys

545 550 555 560

Thr Thr Lys Asp Val Val Gln Thr Ser Ala Gly Ser Ser Glu Ala Lys

565 570 575

Asp Ser Ala Pro Leu Gln Lys Ala Asn Ile Lys Asn Thr Asn Asp Gly

580 585 590

His Thr Gln Ser Gln Asn Asn Lys Asn Thr Gln Glu Asn Lys Ala Lys

595 600 605

Ser Leu Pro Gln Thr Gly Glu Glu Ser Asn Lys Asp Met Thr Leu Pro

610 615 620

Leu Met Ala Leu Leu Ala Leu Ser Ser Ile Val Ala Phe Val Leu Pro

625 630 635 640

Arg Lys Arg Lys Asn

645

<210> 72

<211> 605

<212> PRT

<213> 人工序列

<220>

<223> IsdB -克隆的肽序列

<400> 72

Ala Ala Glu Glu Thr Gly Gly Thr Asn Thr Glu Ala Gln Pro Lys Thr

1 5 10 15

Glu Ala Val Ala Ser Pro Thr Thr Thr Ser Glu Lys Ala Pro Glu Thr

20 25 30

Lys Pro Val Ala Asn Ala Val Ser Val Ser Asn Lys Glu Val Glu Ala

35 40 45

Pro Thr Ser Glu Thr Lys Glu Ala Lys Glu Val Lys Glu Val Lys Ala

50 55 60

Pro Lys Glu Thr Lys Ala Val Lys Pro Ala Ala Lys Ala Thr Asn Asn

65 70 75 80

Thr Tyr Pro Ile Leu Asn Gln Glu Leu Arg Glu Ala Ile Lys Asn Pro

85 90 95

Ala Ile Lys Asp Lys Asp His Ser Ala Pro Asn Ser Arg Pro Ile Asp

100 105 110

Phe Glu Met Lys Lys Glu Asn Gly Glu Gln Gln Phe Tyr His Tyr Ala

115 120 125

Ser Ser Val Lys Pro Ala Arg Val Ile Phe Thr Asp Ser Lys Pro Glu

130 135 140

Ile Glu Leu Gly Leu Gln Ser Gly Gln Phe Trp Arg Lys Phe Glu Val

145 150 155 160

Tyr Glu Gly Asp Lys Lys Leu Pro Ile Lys Leu Val Ser Tyr Asp Thr

165 170 175

Val Lys Asp Tyr Ala Tyr Ile Arg Phe Ser Val Ser Asn Gly Thr Lys

180 185 190

Ala Val Lys Ile Val Ser Ser Thr His Phe Asn Asn Lys Glu Glu Lys

195 200 205

Tyr Asp Tyr Thr Leu Met Glu Phe Ala Gln Pro Ile Tyr Asn Ser Ala

210 215 220

Asp Lys Phe Lys Thr Glu Glu Asp Tyr Lys Ala Glu Lys Leu Leu Ala

225 230 235 240

Pro Tyr Lys Lys Ala Lys Thr Leu Glu Arg Gln Val Tyr Glu Leu Asn

245 250 255

Lys Ile Gln Asp Lys Leu Pro Glu Lys Leu Lys Ala Glu Tyr Lys Lys

260 265 270

Lys Leu Glu Asp Thr Lys Lys Ala Leu Asp Glu Gln Val Lys Ser Ala

275 280 285

Ile Thr Glu Phe Gln Asn Val Gln Pro Thr Asn Glu Lys Met Thr Asp

290 295 300

Leu Gln Asp Thr Lys Tyr Val Val Tyr Glu Ser Val Glu Asn Asn Glu

305 310 315 320

Ser Met Met Asp Thr Phe Val Lys His Pro Ile Lys Thr Gly Met Leu

325 330 335

Asn Gly Lys Lys Tyr Met Val Met Glu Thr Thr Asn Asp Asp Tyr Trp

340 345 350

Lys Asp Phe Met Val Glu Gly Gln Arg Val Arg Thr Ile Ser Lys Asp

355 360 365

Ala Lys Asn Asn Thr Arg Thr Ile Ile Phe Pro Tyr Val Glu Gly Lys

370 375 380

Thr Leu Tyr Asp Ala Ile Val Lys Val His Val Lys Thr Ile Asp Tyr

385 390 395 400

Asp Gly Gln Tyr His Val Arg Ile Val Asp Lys Glu Ala Phe Thr Lys

405 410 415

Ala Asn Thr Asp Lys Ser Asn Lys Lys Glu Gln Gln Asp Asn Ser Ala

420 425 430

Lys Lys Glu Ala Thr Pro Ala Thr Pro Ser Lys Pro Thr Pro Ser Pro

435 440 445

Val Glu Lys Glu Ser Gln Lys Gln Asp Ser Gln Lys Asp Asp Asn Lys

450 455 460

Gln Leu Pro Ser Val Glu Lys Glu Asn Asp Ala Ser Ser Glu Ser Gly

465 470 475 480

Lys Asp Lys Thr Pro Ala Thr Lys Pro Thr Lys Gly Glu Val Glu Ser

485 490 495

Ser Ser Thr Thr Pro Thr Lys Val Val Ser Thr Thr Gln Asn Val Ala

500 505 510

Lys Pro Thr Thr Ala Ser Ser Lys Thr Thr Lys Asp Val Val Gln Thr

515 520 525

Ser Ala Gly Ser Ser Glu Ala Lys Asp Ser Ala Pro Leu Gln Lys Ala

530 535 540

Asn Ile Lys Asn Thr Asn Asp Gly His Thr Gln Ser Gln Asn Asn Lys

545 550 555 560

Asn Thr Gln Glu Asn Lys Ala Lys Ser Leu Pro Gln Thr Gly Glu Glu

565 570 575

Ser Asn Lys Asp Met Thr Leu Pro Leu Met Ala Leu Leu Ala Leu Ser

580 585 590

Ser Ile Val Ala Phe Val Leu Pro Arg Lys Arg Lys Asn

595 600 605

<210> 73

<211> 4158

<212> DNA

<213> 金黄色葡萄球菌

<400> 73

atgctaaaca gagaaaataa aacggcaata acaagaaaag gcatggtatc caatcgatta 60

aataaatttt cgattagaaa gtacacagtg ggaacagcat caattttagt aggtacaaca 120

ttaatttttg gtctggggaa ccaagaagca aaggctgcag aaagtactaa taaagaattg 180

aacgaagcga caacttcagc aagtgataat caatcgagtg ataaagttga tatgcagcaa 240

ctaaatcaag aagacaatac taaaaatgat aatcaaaaag aaatggtatc atctcaaggt 300

aatgaaacga cttcaaatgg gaataaatca atagaaaaag aaagtgtaca atctaccact 360

ggaaataaag ttgaagtttc aactgccaaa tcagatgagc aagcttcacc aaaatctacg 420

aatgaagatt taaacactaa acaaactata agtaatcaag aagggttaca acctgatttg 480

ctagagaata aatcagtggt aaatgttcaa ccaactaatg aggaaaacaa aaaggtagat 540

gcgaaaactg aatcaactac attaaatgtt aaaagtgatg ctatcaagag taatgctgaa 600

actcttgttg ataacaatag taattcaaat aatgaaaata atgcagatat cattttgcca 660

aaaagtacag cacctaaaag tttgaataca agaatgcgta tggcagcaat acaaccaaac 720

tcaacagatt ctaaaaatgt taatgattta atcacatcaa atacaacatt aactgtcgtt 780

gatgcagata atagcaaaac gattgtacca gcccaagatt atttatcatt aaaatcacaa 840

attacagttg atgacaaagt taaatcaggt gattatttca caattaaata ctcagataca 900

gtacaagtat atggattgaa tccggaagat attaaaaata ttggtgatat taaagatcca 960

aataatggtg aaacaattgc gactgcaaaa catgatactg caaataattt aattacatat 1020

acatttacag attatgttga tcgatttaat tcagtaaaaa tgggtattaa ttactcaatt 1080

tatatggatg cagatacaat tcctgttgac aagaaagatg ttccttttag tgtaactatt 1140

ggaaatcaaa ttacaactac aacagcagat atcacttatc cggcttataa agaagctgac 1200

aataattcaa taggatcagc ttttacagag acagtttctc atgtaggaaa tgttgaagac 1260

cctggttact ataaccaggt agtatatgtt aatcctatgg ataaggattt aaaaggtgct 1320

aagttaaaag ttgaagcgta ccatccgaaa tatccaacta atattggtca aattaatcaa 1380

aatgttacaa atataaaaat atatcgtgtt cctgaaggat atacattgaa taaaggatat 1440

gacgttaata ctaatgattt ggtagacgta actgatgaat ttaaaaataa aatgacgtat 1500

ggatcaaatc aaagtgttaa tcttgatttt ggtgatatta catcagcata tgttgtaatg 1560

gttaatacaa aattccaata tacaaatagc gaaagcccaa cacttgttca aatggctact 1620

ttatcttcaa caggtaataa atccgtttct actggcaatg ctttaggatt tactaataac 1680

caaagtggcg gagctggtca agaagtatat aaaattggta actacgtatg ggaagatact 1740

aataaaaacg gtgttcaaga attaggagaa aaaggcgttg gcaatgtaac tgtaactgta 1800

tttgataata atacaaatac aaaagtagga gaagcagtta ctaaagaaga tgggtcatac 1860

ttgattccaa acttacctaa tggagattac cgtgtagaat tttcaaactt accaaaaggt 1920

tatgaagtaa ccccttcaaa acaaggtaat aacgaagaat tagattcaaa cggcttatct 1980

tcagttatta cagttaatgg caaagataac ttatctgcag acttaggtat ttacaaacct 2040

aaatacaact taggtgacta tgtctgggaa gatacaaata aaaatggtat ccaagaccaa 2100

gatgaaaaag gtatatctgg cgtaacggta acattaaaag atgaaaacgg taacgtgtta 2160

aaaacagtta caacagacgc agatggcaaa tataaattta ctgatttaga taatggtaat 2220

tataaagttg aatttactac accagaaggc tatacaccga ctacagtaac atctggtagc 2280

gacattgaaa aagactctaa tggtttaaca acaacaggtg ttattaatgg tgctgataac 2340

atgacattag atagtggatt ctacaaaaca ccaaaatata atttaggtaa ttatgtatgg 2400

gaagatacaa ataaagatgg taagcaggat tcaactgaaa aaggtatttc aggcgtaaca 2460

gttacattga aaaatgaaaa cggtgaagtt ttacaaacaa ctaaaacaga taaagatggt 2520

aaatatcaat ttactggatt agaaaatgga acttataaag ttgaattcga aacaccatca 2580

ggttacacac caacacaagt aggttcagga actgatgaag gtatagattc aaatggtaca 2640

tcaacaacag gtgtcattaa agataaagat aacgatacta ttgactctgg tttctacaaa 2700

ccgacttaca acttaggtga ctatgtatgg gaagatacaa ataaaaacgg tgttcaagat 2760

aaagatgaaa agggtatttc aggtgtaaca gttacgttaa aagatgaaaa cgacaaagtt 2820

ttaaaaacag ttacaacaga tgaaaatggt aaatatcaat tcactgattt aaacaatgga 2880

acttataaag ttgaattcga gacaccatca ggttatacac caacttcagt aacttctgga 2940

aatgatactg aaaaagattc taatggttta acaacaacag gtgtcattaa agatgcagat 3000

aacatgacat tagacagtgg tttctataaa acaccaaaat atagtttagg tgattatgtt 3060

tggtacgaca gtaataaaga cggcaaacaa gattcaactg aaaaaggtat caaagatgtt 3120

aaagttattt tattaaatga aaaaggcgaa gtaattggaa caactaaaac agatgaaaat 3180

ggtaaatacc gctttgataa tttagatagc ggtaaataca aagttatttt tgaaaagcct 3240

actggcttaa cacaaacagg tacaaataca actgaagatg ataaagatgc cgatggtggc 3300

gaagttgatg taacaattac ggatcatgat gatttcacac ttgataatgg ctactacgaa 3360

gaagaaacat cagatagcga ctcagattcg gacagcgatt cagactcaga cagcgattca 3420

gactcagata gtgattcaga ttcagatagt gattcagatt cagatagtga ttcagattca 3480

gacagcgact cagactcaga tagtgactca gactcagata gcgattcaga ttcagatagc 3540

gattcagact cagacagcga ttcagattca gacagcgact cagactcaga tagcgactca 3600

gattcggaca gcgattcaga ctcagatagc gactcagact cagacagcga ttcagactca 3660

gatagcgact cagactcaga tagcgattca gattcagaca gcgattcaga ttcagacagt 3720

gattcagatt cagacagcga ctcagattca gatagcgatt cagactcaga ctcagatagc 3780

gattcagatt cagacagcga ctcagattcg gacagcgact cagactcaga cagtgattca 3840

gattcagata gcgactcaga ctcagatagc gactcagatt cagacagcga ttcagactca 3900

gatagtgact cagattcgga cagcgattca gactcagata gcgactcaga ttcagacagt 3960

gattcagact cagatgcagg taagcacaca cctgttaaac caatgagtac tactaaagac 4020

catcacaata aagcaaaagc attaccagaa actggtaatg aaaatagtgg ctcaaataac 4080

gcaacgttat ttggcggatt attcgcagca ttaggatcat tattgttatt cggtcgtcgt 4140

aaaaaacaaa ataaataa 4158

<210> 74

<211> 2385

<212> DNA

<213> 人工序列

<220>

<223> SdrD -部分克隆的DNA序列

<400> 74

ggcgttggca atgtaactgt aactgtattt gataataata caaatacaaa agtaggagaa 60

gcagttacta aagaagatgg gtcatacttg attccaaact tacctaatgg agattaccgt 120

gtagaatttt caaacttacc aaaaggttat gaagtaaccc cttcaaaaca aggtaataac 180

gaagaattag attcaaacgg cttatcttca gttattacag ttaatggcaa agataactta 240

tctgcagact taggtattta caaacctaaa tacaacttag gtgactatgt ctgggaagat 300

acaaataaaa atggtatcca agaccaagat gaaaaaggta tatctggcgt aacggtaaca 360

ttaaaagatg aaaacggtaa cgtgttaaaa acagttacaa cagacgcaga tggcaaatat 420

aaatttactg atttagataa tggtaattat aaagttgaat ttactacacc agaaggctat 480

acaccgacta cagtaacatc tggtagcgac attgaaaaag actctaatgg tttaacaaca 540

acaggtgtta ttaatggtgc tgataacatg acattagata gtggattcta caaaacacca 600

aaatataatt taggtaatta tgtatgggaa gatacaaata aagatggtaa gcaggattca 660

actgaaaaag gtatttcagg cgtaacagtt acattgaaaa atgaaaacgg tgaagtttta 720

caaacaacta aaacagataa agatggtaaa tatcaattta ctggattaga aaatggaact 780

tataaagttg aattcgaaac accatcaggt tacacaccaa cacaagtagg ttcaggaact 840

gatgaaggta tagattcaaa tggtacatca acaacaggtg tcattaaaga taaagataac 900

gatactattg actctggttt ctacaaaccg acttacaact taggtgacta tgtatgggaa 960

gatacaaata aaaacggtgt tcaagataaa gatgaaaagg gtatttcagg tgtaacagtt 1020

acgttaaaag atgaaaacga caaagtttta aaaacagtta caacagatga aaatggtaaa 1080

tatcaattca ctgatttaaa caatggaact tataaagttg aattcgagac accatcaggt 1140

tatacaccaa cttcagtaac ttctggaaat gatactgaaa aagattctaa tggtttaaca 1200

acaacaggtg tcattaaaga tgcagataac atgacattag acagtggttt ctataaaaca 1260

ccaaaatata gtttaggtga ttatgtttgg tacgacagta ataaagacgg caaacaagat 1320

tcaactgaaa aaggtatcaa agatgttaaa gttattttat taaatgaaaa aggcgaagta 1380

attggaacaa ctaaaacaga tgaaaatggt aaataccgct ttgataattt agatagcggt 1440

aaatacaaag ttatttttga aaagcctact ggcttaacac aaacaggtac aaatacaact 1500

gaagatgata aagatgccga tggtggcgaa gttgatgtaa caattacgga tcatgatgat 1560

ttcacacttg ataatggcta ctacgaagaa gaaacatcag atagcgactc agattcggac 1620

agcgattcag actcagacag cgattcagac tcagatagtg attcagattc agatagtgat 1680

tcagattcag atagtgattc agattcagac agcgactcag actcagatag tgactcagac 1740

tcagatagcg attcagattc agatagcgat tcagactcag acagcgattc agattcagac 1800

agcgactcag actcagatag cgactcagat tcggacagcg attcagactc agatagcgac 1860

tcagactcag acagcgattc agactcagat agcgactcag actcagatag cgattcagat 1920

tcagacagcg attcagattc agacagtgat tcagattcag acagcgactc agattcagat 1980

agcgattcag actcagactc agatagcgat tcagattcag acagcgactc agattcggac 2040

agcgactcag actcagacag tgattcagat tcagatagcg actcagactc agatagcgac 2100

tcagattcag acagcgattc agactcagat agtgactcag attcggacag cgattcagac 2160

tcagatagcg actcagattc agacagtgat tcagactcag atgcaggtaa gcacacacct 2220

gttaaaccaa tgagtactac taaagaccat cacaataaag caaaagcatt accagaaact 2280

ggtaatgaaa atagtggctc aaataacgca acgttatttg gcggattatt cgcagcatta 2340

ggatcattat tgttattcgg tcgtcgtaaa aaacaaaata aataa 2385

<210> 75

<211> 1524

<212> DNA

<213> 人工序列

<220>

<223> SdrD -部分克隆的DNA序列

<400> 75

ggagaaaaag gcgttggcaa tgtaactgta actgtatttg ataataatac aaatacaaaa 60

gtaggagaag cagttactaa agaagatggg tcatacttga ttccaaactt acctaatgga 120

gattaccgtg tagaattttc aaacttacca aaaggttatg aagtaacccc ttcaaaacaa 180

ggtaataacg aagaattaga ttcaaacggc ttatcttcag ttattacagt taatggcaaa 240

gataacttat ctgcagactt aggtatttac aaacctaaat acaacttagg tgactatgtc 300

tgggaagata caaataaaaa tggtatccaa gaccaagatg aaaaaggtat atctggcgta 360

acggtaacat taaaagatga aaacggtaac gtgttaaaaa cagttacaac agacgcagat 420

ggcaaatata aatttactga tttagataat ggtaattata aagttgaatt tactacacca 480

gaaggctata caccgactac agtaacatct ggtagcgaca ttgaaaaaga ctctaatggt 540

ttaacaacaa caggtgttat taatggtgct gataacatga cattagatag tggattctac 600

aaaacaccaa aatataattt aggtaattat gtatgggaag atacaaataa agatggtaag 660

caggattcaa ctgaaaaagg tatttcaggc gtaacagtta cattgaaaaa tgaaaacggt 720

gaagttttac aaacaactaa aacagataaa gatggtaaat atcaatttac tggattagaa 780

aatggaactt ataaagttga attcgaaaca ccatcaggtt acacaccaac acaagtaggt 840

tcaggaactg atgaaggtat agattcaaat ggtacatcaa caacaggtgt cattaaagat 900

aaagataacg atactattga ctctggtttc tacaaaccga cttacaactt aggtgactat 960

gtatgggaag atacaaataa aaacggtgtt caagataaag atgaaaaggg tatttcaggt 1020

gtaacagtta cgttaaaaga tgaaaacgac aaagttttaa aaacagttac aacagatgaa 1080

aatggtaaat atcaattcac tgatttaaac aatggaactt ataaagttga attcgagaca 1140

ccatcaggtt atacaccaac ttcagtaact tctggaaatg atactgaaaa agattctaat 1200

ggtttaacaa caacaggtgt cattaaagat gcagataaca tgacattaga cagtggtttc 1260

tataaaacac caaaatatag tttaggtgat tatgtttggt acgacagtaa taaagacggc 1320

aaacaagatt caactgaaaa aggtatcaaa gatgttaaag ttattttatt aaatgaaaaa 1380

ggcgaagtaa ttggaacaac taaaacagat gaaaatggta aataccgctt tgataattta 1440

gatagcggta aatacaaagt tatttttgaa aagcctactg gcttaacaca aacaggtaca 1500

aatacaactg aagatgataa ataa 1524

<210> 76

<211> 1385

<212> PRT

<213> 金黄色葡萄球菌

<400> 76

Met Leu Asn Arg Glu Asn Lys Thr Ala Ile Thr Arg Lys Gly Met Val

1 5 10 15

Ser Asn Arg Leu Asn Lys Phe Ser Ile Arg Lys Tyr Thr Val Gly Thr

20 25 30

Ala Ser Ile Leu Val Gly Thr Thr Leu Ile Phe Gly Leu Gly Asn Gln

35 40 45

Glu Ala Lys Ala Ala Glu Ser Thr Asn Lys Glu Leu Asn Glu Ala Thr

50 55 60

Thr Ser Ala Ser Asp Asn Gln Ser Ser Asp Lys Val Asp Met Gln Gln

65 70 75 80

Leu Asn Gln Glu Asp Asn Thr Lys Asn Asp Asn Gln Lys Glu Met Val

85 90 95

Ser Ser Gln Gly Asn Glu Thr Thr Ser Asn Gly Asn Lys Ser Ile Glu

100 105 110

Lys Glu Ser Val Gln Ser Thr Thr Gly Asn Lys Val Glu Val Ser Thr

115 120 125

Ala Lys Ser Asp Glu Gln Ala Ser Pro Lys Ser Thr Asn Glu Asp Leu

130 135 140

Asn Thr Lys Gln Thr Ile Ser Asn Gln Glu Gly Leu Gln Pro Asp Leu

145 150 155 160

Leu Glu Asn Lys Ser Val Val Asn Val Gln Pro Thr Asn Glu Glu Asn

165 170 175

Lys Lys Val Asp Ala Lys Thr Glu Ser Thr Thr Leu Asn Val Lys Ser

180 185 190

Asp Ala Ile Lys Ser Asn Ala Glu Thr Leu Val Asp Asn Asn Ser Asn

195 200 205

Ser Asn Asn Glu Asn Asn Ala Asp Ile Ile Leu Pro Lys Ser Thr Ala

210 215 220

Pro Lys Ser Leu Asn Thr Arg Met Arg Met Ala Ala Ile Gln Pro Asn

225 230 235 240

Ser Thr Asp Ser Lys Asn Val Asn Asp Leu Ile Thr Ser Asn Thr Thr

245 250 255

Leu Thr Val Val Asp Ala Asp Asn Ser Lys Thr Ile Val Pro Ala Gln

260 265 270

Asp Tyr Leu Ser Leu Lys Ser Gln Ile Thr Val Asp Asp Lys Val Lys

275 280 285

Ser Gly Asp Tyr Phe Thr Ile Lys Tyr Ser Asp Thr Val Gln Val Tyr

290 295 300

Gly Leu Asn Pro Glu Asp Ile Lys Asn Ile Gly Asp Ile Lys Asp Pro

305 310 315 320

Asn Asn Gly Glu Thr Ile Ala Thr Ala Lys His Asp Thr Ala Asn Asn

325 330 335

Leu Ile Thr Tyr Thr Phe Thr Asp Tyr Val Asp Arg Phe Asn Ser Val

340 345 350

Lys Met Gly Ile Asn Tyr Ser Ile Tyr Met Asp Ala Asp Thr Ile Pro

355 360 365

Val Asp Lys Lys Asp Val Pro Phe Ser Val Thr Ile Gly Asn Gln Ile

370 375 380

Thr Thr Thr Thr Ala Asp Ile Thr Tyr Pro Ala Tyr Lys Glu Ala Asp

385 390 395 400

Asn Asn Ser Ile Gly Ser Ala Phe Thr Glu Thr Val Ser His Val Gly

405 410 415

Asn Val Glu Asp Pro Gly Tyr Tyr Asn Gln Val Val Tyr Val Asn Pro

420 425 430

Met Asp Lys Asp Leu Lys Gly Ala Lys Leu Lys Val Glu Ala Tyr His

435 440 445

Pro Lys Tyr Pro Thr Asn Ile Gly Gln Ile Asn Gln Asn Val Thr Asn

450 455 460

Ile Lys Ile Tyr Arg Val Pro Glu Gly Tyr Thr Leu Asn Lys Gly Tyr

465 470 475 480

Asp Val Asn Thr Asn Asp Leu Val Asp Val Thr Asp Glu Phe Lys Asn

485 490 495

Lys Met Thr Tyr Gly Ser Asn Gln Ser Val Asn Leu Asp Phe Gly Asp

500 505 510

Ile Thr Ser Ala Tyr Val Val Met Val Asn Thr Lys Phe Gln Tyr Thr

515 520 525

Asn Ser Glu Ser Pro Thr Leu Val Gln Met Ala Thr Leu Ser Ser Thr

530 535 540

Gly Asn Lys Ser Val Ser Thr Gly Asn Ala Leu Gly Phe Thr Asn Asn

545 550 555 560

Gln Ser Gly Gly Ala Gly Gln Glu Val Tyr Lys Ile Gly Asn Tyr Val

565 570 575

Trp Glu Asp Thr Asn Lys Asn Gly Val Gln Glu Leu Gly Glu Lys Gly

580 585 590

Val Gly Asn Val Thr Val Thr Val Phe Asp Asn Asn Thr Asn Thr Lys

595 600 605

Val Gly Glu Ala Val Thr Lys Glu Asp Gly Ser Tyr Leu Ile Pro Asn

610 615 620

Leu Pro Asn Gly Asp Tyr Arg Val Glu Phe Ser Asn Leu Pro Lys Gly

625 630 635 640

Tyr Glu Val Thr Pro Ser Lys Gln Gly Asn Asn Glu Glu Leu Asp Ser

645 650 655

Asn Gly Leu Ser Ser Val Ile Thr Val Asn Gly Lys Asp Asn Leu Ser

660 665 670

Ala Asp Leu Gly Ile Tyr Lys Pro Lys Tyr Asn Leu Gly Asp Tyr Val

675 680 685

Trp Glu Asp Thr Asn Lys Asn Gly Ile Gln Asp Gln Asp Glu Lys Gly

690 695 700

Ile Ser Gly Val Thr Val Thr Leu Lys Asp Glu Asn Gly Asn Val Leu

705 710 715 720

Lys Thr Val Thr Thr Asp Ala Asp Gly Lys Tyr Lys Phe Thr Asp Leu

725 730 735

Asp Asn Gly Asn Tyr Lys Val Glu Phe Thr Thr Pro Glu Gly Tyr Thr

740 745 750

Pro Thr Thr Val Thr Ser Gly Ser Asp Ile Glu Lys Asp Ser Asn Gly

755 760 765

Leu Thr Thr Thr Gly Val Ile Asn Gly Ala Asp Asn Met Thr Leu Asp

770 775 780

Ser Gly Phe Tyr Lys Thr Pro Lys Tyr Asn Leu Gly Asn Tyr Val Trp

785 790 795 800

Glu Asp Thr Asn Lys Asp Gly Lys Gln Asp Ser Thr Glu Lys Gly Ile

805 810 815

Ser Gly Val Thr Val Thr Leu Lys Asn Glu Asn Gly Glu Val Leu Gln

820 825 830

Thr Thr Lys Thr Asp Lys Asp Gly Lys Tyr Gln Phe Thr Gly Leu Glu

835 840 845

Asn Gly Thr Tyr Lys Val Glu Phe Glu Thr Pro Ser Gly Tyr Thr Pro

850 855 860

Thr Gln Val Gly Ser Gly Thr Asp Glu Gly Ile Asp Ser Asn Gly Thr

865 870 875 880

Ser Thr Thr Gly Val Ile Lys Asp Lys Asp Asn Asp Thr Ile Asp Ser

885 890 895

Gly Phe Tyr Lys Pro Thr Tyr Asn Leu Gly Asp Tyr Val Trp Glu Asp

900 905 910

Thr Asn Lys Asn Gly Val Gln Asp Lys Asp Glu Lys Gly Ile Ser Gly

915 920 925

Val Thr Val Thr Leu Lys Asp Glu Asn Asp Lys Val Leu Lys Thr Val

930 935 940

Thr Thr Asp Glu Asn Gly Lys Tyr Gln Phe Thr Asp Leu Asn Asn Gly

945 950 955 960

Thr Tyr Lys Val Glu Phe Glu Thr Pro Ser Gly Tyr Thr Pro Thr Ser

965 970 975

Val Thr Ser Gly Asn Asp Thr Glu Lys Asp Ser Asn Gly Leu Thr Thr

980 985 990

Thr Gly Val Ile Lys Asp Ala Asp Asn Met Thr Leu Asp Ser Gly Phe

995 1000 1005

Tyr Lys Thr Pro Lys Tyr Ser Leu Gly Asp Tyr Val Trp Tyr Asp

1010 1015 1020

Ser Asn Lys Asp Gly Lys Gln Asp Ser Thr Glu Lys Gly Ile Lys

1025 1030 1035

Asp Val Lys Val Ile Leu Leu Asn Glu Lys Gly Glu Val Ile Gly

1040 1045 1050

Thr Thr Lys Thr Asp Glu Asn Gly Lys Tyr Arg Phe Asp Asn Leu

1055 1060 1065

Asp Ser Gly Lys Tyr Lys Val Ile Phe Glu Lys Pro Thr Gly Leu

1070 1075 1080

Thr Gln Thr Gly Thr Asn Thr Thr Glu Asp Asp Lys Asp Ala Asp

1085 1090 1095

Gly Gly Glu Val Asp Val Thr Ile Thr Asp His Asp Asp Phe Thr

1100 1105 1110

Leu Asp Asn Gly Tyr Tyr Glu Glu Glu Thr Ser Asp Ser Asp Ser

1115 1120 1125

Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp

1130 1135 1140

Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser

1145 1150 1155

Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp

1160 1165 1170

Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser

1175 1180 1185

Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp

1190 1195 1200

Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser

1205 1210 1215

Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp

1220 1225 1230

Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser

1235 1240 1245

Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp

1250 1255 1260

Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser

1265 1270 1275

Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp

1280 1285 1290

Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser

1295 1300 1305

Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp

1310 1315 1320

Ser Asp Ala Gly Lys His Thr Pro Val Lys Pro Met Ser Thr Thr

1325 1330 1335

Lys Asp His His Asn Lys Ala Lys Ala Leu Pro Glu Thr Gly Asn

1340 1345 1350

Glu Asn Ser Gly Ser Asn Asn Ala Thr Leu Phe Gly Gly Leu Phe

1355 1360 1365

Ala Ala Leu Gly Ser Leu Leu Leu Phe Gly Arg Arg Lys Lys Gln

1370 1375 1380

Asn Lys

1385

<210> 77

<211> 794

<212> PRT

<213> 人工序列

<220>

<223> SdrD -部分克隆的肽序列

<400> 77

Gly Val Gly Asn Val Thr Val Thr Val Phe Asp Asn Asn Thr Asn Thr

1 5 10 15

Lys Val Gly Glu Ala Val Thr Lys Glu Asp Gly Ser Tyr Leu Ile Pro

20 25 30

Asn Leu Pro Asn Gly Asp Tyr Arg Val Glu Phe Ser Asn Leu Pro Lys

35 40 45

Gly Tyr Glu Val Thr Pro Ser Lys Gln Gly Asn Asn Glu Glu Leu Asp

50 55 60

Ser Asn Gly Leu Ser Ser Val Ile Thr Val Asn Gly Lys Asp Asn Leu

65 70 75 80

Ser Ala Asp Leu Gly Ile Tyr Lys Pro Lys Tyr Asn Leu Gly Asp Tyr

85 90 95

Val Trp Glu Asp Thr Asn Lys Asn Gly Ile Gln Asp Gln Asp Glu Lys

100 105 110

Gly Ile Ser Gly Val Thr Val Thr Leu Lys Asp Glu Asn Gly Asn Val

115 120 125

Leu Lys Thr Val Thr Thr Asp Ala Asp Gly Lys Tyr Lys Phe Thr Asp

130 135 140

Leu Asp Asn Gly Asn Tyr Lys Val Glu Phe Thr Thr Pro Glu Gly Tyr

145 150 155 160

Thr Pro Thr Thr Val Thr Ser Gly Ser Asp Ile Glu Lys Asp Ser Asn

165 170 175

Gly Leu Thr Thr Thr Gly Val Ile Asn Gly Ala Asp Asn Met Thr Leu

180 185 190

Asp Ser Gly Phe Tyr Lys Thr Pro Lys Tyr Asn Leu Gly Asn Tyr Val

195 200 205

Trp Glu Asp Thr Asn Lys Asp Gly Lys Gln Asp Ser Thr Glu Lys Gly

210 215 220

Ile Ser Gly Val Thr Val Thr Leu Lys Asn Glu Asn Gly Glu Val Leu

225 230 235 240

Gln Thr Thr Lys Thr Asp Lys Asp Gly Lys Tyr Gln Phe Thr Gly Leu

245 250 255

Glu Asn Gly Thr Tyr Lys Val Glu Phe Glu Thr Pro Ser Gly Tyr Thr

260 265 270

Pro Thr Gln Val Gly Ser Gly Thr Asp Glu Gly Ile Asp Ser Asn Gly

275 280 285

Thr Ser Thr Thr Gly Val Ile Lys Asp Lys Asp Asn Asp Thr Ile Asp

290 295 300

Ser Gly Phe Tyr Lys Pro Thr Tyr Asn Leu Gly Asp Tyr Val Trp Glu

305 310 315 320

Asp Thr Asn Lys Asn Gly Val Gln Asp Lys Asp Glu Lys Gly Ile Ser

325 330 335

Gly Val Thr Val Thr Leu Lys Asp Glu Asn Asp Lys Val Leu Lys Thr

340 345 350

Val Thr Thr Asp Glu Asn Gly Lys Tyr Gln Phe Thr Asp Leu Asn Asn

355 360 365

Gly Thr Tyr Lys Val Glu Phe Glu Thr Pro Ser Gly Tyr Thr Pro Thr

370 375 380

Ser Val Thr Ser Gly Asn Asp Thr Glu Lys Asp Ser Asn Gly Leu Thr

385 390 395 400

Thr Thr Gly Val Ile Lys Asp Ala Asp Asn Met Thr Leu Asp Ser Gly

405 410 415

Phe Tyr Lys Thr Pro Lys Tyr Ser Leu Gly Asp Tyr Val Trp Tyr Asp

420 425 430

Ser Asn Lys Asp Gly Lys Gln Asp Ser Thr Glu Lys Gly Ile Lys Asp

435 440 445

Val Lys Val Ile Leu Leu Asn Glu Lys Gly Glu Val Ile Gly Thr Thr

450 455 460

Lys Thr Asp Glu Asn Gly Lys Tyr Arg Phe Asp Asn Leu Asp Ser Gly

465 470 475 480

Lys Tyr Lys Val Ile Phe Glu Lys Pro Thr Gly Leu Thr Gln Thr Gly

485 490 495

Thr Asn Thr Thr Glu Asp Asp Lys Asp Ala Asp Gly Gly Glu Val Asp

500 505 510

Val Thr Ile Thr Asp His Asp Asp Phe Thr Leu Asp Asn Gly Tyr Tyr

515 520 525

Glu Glu Glu Thr Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp

530 535 540

Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp

545 550 555 560

Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp

565 570 575

Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp

580 585 590

Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp

595 600 605

Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp

610 615 620

Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp

625 630 635 640

Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp

645 650 655

Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp

660 665 670

Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp

675 680 685

Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp

690 695 700

Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp

705 710 715 720

Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ala Gly

725 730 735

Lys His Thr Pro Val Lys Pro Met Ser Thr Thr Lys Asp His His Asn

740 745 750

Lys Ala Lys Ala Leu Pro Glu Thr Gly Asn Glu Asn Ser Gly Ser Asn

755 760 765

Asn Ala Thr Leu Phe Gly Gly Leu Phe Ala Ala Leu Gly Ser Leu Leu

770 775 780

Leu Phe Gly Arg Arg Lys Lys Gln Asn Lys

785 790

<210> 78

<211> 507

<212> PRT

<213> 人工序列

<220>

<223> SdrD -部分克隆的肽序列

<400> 78

Gly Glu Lys Gly Val Gly Asn Val Thr Val Thr Val Phe Asp Asn Asn

1 5 10 15

Thr Asn Thr Lys Val Gly Glu Ala Val Thr Lys Glu Asp Gly Ser Tyr

20 25 30

Leu Ile Pro Asn Leu Pro Asn Gly Asp Tyr Arg Val Glu Phe Ser Asn

35 40 45

Leu Pro Lys Gly Tyr Glu Val Thr Pro Ser Lys Gln Gly Asn Asn Glu

50 55 60

Glu Leu Asp Ser Asn Gly Leu Ser Ser Val Ile Thr Val Asn Gly Lys

65 70 75 80

Asp Asn Leu Ser Ala Asp Leu Gly Ile Tyr Lys Pro Lys Tyr Asn Leu

85 90 95

Gly Asp Tyr Val Trp Glu Asp Thr Asn Lys Asn Gly Ile Gln Asp Gln

100 105 110

Asp Glu Lys Gly Ile Ser Gly Val Thr Val Thr Leu Lys Asp Glu Asn

115 120 125

Gly Asn Val Leu Lys Thr Val Thr Thr Asp Ala Asp Gly Lys Tyr Lys

130 135 140

Phe Thr Asp Leu Asp Asn Gly Asn Tyr Lys Val Glu Phe Thr Thr Pro

145 150 155 160

Glu Gly Tyr Thr Pro Thr Thr Val Thr Ser Gly Ser Asp Ile Glu Lys

165 170 175

Asp Ser Asn Gly Leu Thr Thr Thr Gly Val Ile Asn Gly Ala Asp Asn

180 185 190

Met Thr Leu Asp Ser Gly Phe Tyr Lys Thr Pro Lys Tyr Asn Leu Gly

195 200 205

Asn Tyr Val Trp Glu Asp Thr Asn Lys Asp Gly Lys Gln Asp Ser Thr

210 215 220

Glu Lys Gly Ile Ser Gly Val Thr Val Thr Leu Lys Asn Glu Asn Gly

225 230 235 240

Glu Val Leu Gln Thr Thr Lys Thr Asp Lys Asp Gly Lys Tyr Gln Phe

245 250 255

Thr Gly Leu Glu Asn Gly Thr Tyr Lys Val Glu Phe Glu Thr Pro Ser

260 265 270

Gly Tyr Thr Pro Thr Gln Val Gly Ser Gly Thr Asp Glu Gly Ile Asp

275 280 285

Ser Asn Gly Thr Ser Thr Thr Gly Val Ile Lys Asp Lys Asp Asn Asp

290 295 300

Thr Ile Asp Ser Gly Phe Tyr Lys Pro Thr Tyr Asn Leu Gly Asp Tyr

305 310 315 320

Val Trp Glu Asp Thr Asn Lys Asn Gly Val Gln Asp Lys Asp Glu Lys

325 330 335

Gly Ile Ser Gly Val Thr Val Thr Leu Lys Asp Glu Asn Asp Lys Val

340 345 350

Leu Lys Thr Val Thr Thr Asp Glu Asn Gly Lys Tyr Gln Phe Thr Asp

355 360 365

Leu Asn Asn Gly Thr Tyr Lys Val Glu Phe Glu Thr Pro Ser Gly Tyr

370 375 380

Thr Pro Thr Ser Val Thr Ser Gly Asn Asp Thr Glu Lys Asp Ser Asn

385 390 395 400

Gly Leu Thr Thr Thr Gly Val Ile Lys Asp Ala Asp Asn Met Thr Leu

405 410 415

Asp Ser Gly Phe Tyr Lys Thr Pro Lys Tyr Ser Leu Gly Asp Tyr Val

420 425 430

Trp Tyr Asp Ser Asn Lys Asp Gly Lys Gln Asp Ser Thr Glu Lys Gly

435 440 445

Ile Lys Asp Val Lys Val Ile Leu Leu Asn Glu Lys Gly Glu Val Ile

450 455 460

Gly Thr Thr Lys Thr Asp Glu Asn Gly Lys Tyr Arg Phe Asp Asn Leu

465 470 475 480

Asp Ser Gly Lys Tyr Lys Val Ile Phe Glu Lys Pro Thr Gly Leu Thr

485 490 495

Gln Thr Gly Thr Asn Thr Thr Glu Asp Asp Lys

500 505

<210> 79

<211> 2808

<212> DNA

<213> 金黄色葡萄球菌

<400> 79

atgaatatga agaaaaaaga aaaacacgca attcggaaaa aatcgattgg cgtggcttca 60

gtgcttgtag gtacgttaat cggttttgga ctactcagca gtaaagaagc agatgcaagt 120

gaaaatagtg ttacgcaatc tgatagcgca agtaacgaaa gcaaaagtaa tgattcaagt 180

agcgttagtg ctgcacctaa aacagacgac acaaacgtga gtgatactaa aacatcgtca 240

aacactaata atggcgaaac gagtgtggcg caaaatccag cacaacagga aacgacacaa 300

tcatcatcaa caaatgcaac tacggaagaa acgccggtaa ctggtgaagc tactactacg 360

acaacgaatc aagctaatac accggcaaca actcaatcaa gcaatacaaa tgcggaggaa 420

ttagtgaatc aaacaagtaa tgaaacgact tctaatgata ctaatacagt atcatctgta 480

aattcacctc aaaattctac aaatgcggaa aatgtttcaa caacgcaaga tacttcaact 540

gaagcaacac cttcaaacaa tgaatcagct ccacagaata cagatgcaag taataaagat 600

gtagttagtc aagcggttaa tccaagtacg cctagaatga gagcatttag tttagcggca 660

gtagctgcag atgcaccggc agctggcaca gatattacga atcagttgac agatgtgaaa 720

gttactattg actctggtac gactgtgtat ccgcaccaag caggttatgt caaactgaat 780

tatggttttt cagtgcctaa ttctgctgtt aaaggtgaca cattcaaaat aactgtacct 840

aaagaattaa acttaaatgg tgtaacttca actgctaaag tgccaccaat tatggctgga 900

gatcaagtat tggcaaatgg tgtaatcgat agtgatggta atgttattta tacatttaca 960

gactatgttg ataataaaga aaatgtaaca gctaatatta ctatgccagc ttatattgac 1020

cctgaaaatg ttacaaagac aggtaatgtg acattgacaa ctggcatagg aaccaatact 1080

gctagtaaga cagtattaat cgactatgag aaatatggac aattccataa tttatcaatt 1140

aaaggtacga ttgatcaaat cgataaaaca aataatacgt atcgccaaac aatttatgtc 1200

aatccaagcg gagataacgt tgtgttacct gccttaacag gtaatttaat tcctaataca 1260

aagagtaatg cgttaataga tgcaaaaaac actgatatta aagtttatag agtcgataat 1320

gctaatgatt tatctgaaag ttattatgtg aatcctagcg attttgaaga tgtaactaat 1380

caagttagaa tttcatttcc aaatgctaat caatacaaag tagaatttcc tacggacgat 1440

gaccaaatta caacaccgta tattgtagtt gttaatggcc atattgatcc tgctagtaca 1500

ggtgatttag cactacgttc gacattttat ggttatgatt ctaattttat atggagatct 1560

atgtcatggg acaacgaagt agcatttaat aacggatcag gttctggtga cggtatcgat 1620

aaaccagttg ttcctgaaca acctgatgag cctggtgaaa ttgaaccaat tccagaggat 1680

tcagattctg acccaggttc agattctggc agcgattcta attcagatag cggttcagat 1740

tctggcagtg attctacatc agatagtggt tcagattcag cgagtgattc agattcagca 1800

agtgattcag actcagcgag tgattcagat tcagcaagtg attcagattc agcaagtgat 1860

tcagattcag caagtgattc agactcagca agtgattcag attcagcaag tgattcagat 1920

tcagcaagcg attcagattc agcgagcgat tcagattcag cgagcgattc agattcagcg 1980

agtgattccg actcagcgag cgattcagac tcagatagtg actcagattc cgatagcgat 2040

tccgactcag atagcgactc agattcagac agcgattctg actcagacag cgattctgac 2100

tcagacagtg actcagattc cgatagcgat tctgactcag acagtgactc agattccgat 2160

agcgattcag attcagacag tgattcagac tcagatagcg attcagattc cgacagtgac 2220

tcagactcag acagcgattc agattccgat agcgattcag attccgacag tgactcagat 2280

tccgatagtg actcggattc agcgagtgat tcagattcag atagcgattc agaatcagat 2340

agtgactcag actcagacag tgattcagat tcagatagtg actcagactc agacagcgat 2400

tcagaatcag atagtgactc cgattcagac agcgattcag aatcagatag tgactccgat 2460

tcagatagcg attcggattc agcgagtgat tcagactcag gtagtgactc cgattcatca 2520

agtgattcag attccgattc aacgagtgac acaggatcag acaacgactc agacagtgat 2580

tcaaatagcg attccgagtc aggttctaac aataatgtag ttccgcctaa ttcacctaaa 2640

aatggtacta atgcttctaa taaaaatgag gctaaagata gtaaagaacc attaccagat 2700

acaggttctg aagatgaagc gaatacgtca ctaatttggg gattattagc atcattaggt 2760

tcattactac ttttcagaag aaaaaaagaa aataaagata agaaataa 2808

<210> 80

<211> 1638

<212> DNA

<213> 人工序列

<220>

<223> ClfA -部分克隆的DNA序列

<400> 80

gaaaatagtg ttacgcaatc tgatagcgca agtaacgaaa gcaaaagtaa tgattcaagt 60

agcgttagtg ctgcacctaa aacagacgac acaaacgtga gtgatactaa aacatcgtca 120

aacactaata atggcgaaac gagtgtggcg caaaatccag cacaacagga aacgacacaa 180

tcatcatcaa caaatgcaac tacggaagaa acgccggtaa ctggtgaagc tactactacg 240

acaacgaatc aagctaatac accggcaaca actcaatcaa gcaatacaaa tgcggaggaa 300

ttagtgaatc aaacaagtaa tgaaacgact tctaatgata ctaatacagt atcatctgta 360

aattcacctc aaaattctac aaatgcggaa aatgtttcaa caacgcaaga tacttcaact 420

gaagcaacac cttcaaacaa tgaatcagct ccacagaata cagatgcaag taataaagat 480

gtagttagtc aagcggttaa tccaagtacg cctagaatga gagcatttag tttagcggca 540

gtagctgcag atgcaccggc agctggcaca gatattacga atcagttgac agatgtgaaa 600

gttactattg actctggtac gactgtgtat ccgcaccaag caggttatgt caaactgaat 660

tatggttttt cagtgcctaa ttctgctgtt aaaggtgaca cattcaaaat aactgtacct 720

aaagaattaa acttaaatgg tgtaacttca actgctaaag tgccaccaat tatggctgga 780

gatcaagtat tggcaaatgg tgtaatcgat agtgatggta atgttattta tacatttaca 840

gactatgttg ataataaaga aaatgtaaca gctaatatta ctatgccagc ttatattgac 900

cctgaaaatg ttacaaagac aggtaatgtg acattgacaa ctggcatagg aaccaatact 960

gctagtaaga cagtattaat cgactatgag aaatatggac aattccataa tttatcaatt 1020

aaaggtacga ttgatcaaat cgataaaaca aataatacgt atcgccaaac aatttatgtc 1080

aatccaagcg gagataacgt tgtgttacct gccttaacag gtaatttaat tcctaataca 1140

aagagtaatg cgttaataga tgcaaaaaac actgatatta aagtttatag agtcgataat 1200

gctaatgatt tatctgaaag ttattatgtg aatcctagcg attttgaaga tgtaactaat 1260

caagttagaa tttcatttcc aaatgctaat caatacaaag tagaatttcc tacggacgat 1320

gaccaaatta caacaccgta tattgtagtt gttaatggcc atattgatcc tgctagtaca 1380

ggtgatttag cactacgttc gacattttat ggttatgatt ctaattttat atggagatct 1440

atgtcatggg acaacgaagt agcatttaat aacggatcag gttctggtga cggtatcgat 1500

aaaccagttg ttcctgaaca acctgatgag cctggtgaaa ttgaaccaat tccagaggat 1560

tcagattctg acccaggttc agattctggc agcgattcta attcagatag cggttcagat 1620

tctggcagtg attcttaa 1638

<210> 81

<211> 1353

<212> DNA

<213> 人工序列

<220>

<223> ClfA -部分克隆的DNA序列

<400> 81

ccgtatattg tagttgttaa tggccatatt gatcctgcta gtacaggtga tttagcacta 60

cgttcgacat tttatggtta tgattctaat tttatatgga gatctatgtc atgggacaac 120

gaagtagcat ttaataacgg atcaggttct ggtgacggta tcgataaacc agttgttcct 180

gaacaacctg atgagcctgg tgaaattgaa ccaattccag aggattcaga ttctgaccca 240

ggttcagatt ctggcagcga ttctaattca gatagcggtt cagattctgg cagtgattct 300

acatcagata gtggttcaga ttcagcgagt gattcagatt cagcaagtga ttcagactca 360

gcgagtgatt cagattcagc aagtgattca gattcagcaa gtgattcaga ttcagcaagt 420

gattcagact cagcaagtga ttcagattca gcaagtgatt cagattcagc aagcgattca 480

gattcagcga gcgattcaga ttcagcgagc gattcagatt cagcgagtga ttccgactca 540

gcgagcgatt cagactcaga tagtgactca gattccgata gcgattccga ctcagatagc 600

gactcagatt cagacagcga ttctgactca gacagcgatt ctgactcaga cagtgactca 660

gattccgata gcgattctga ctcagacagt gactcagatt ccgatagcga ttcagattca 720

gacagtgatt cagactcaga tagcgattca gattccgaca gtgactcaga ctcagacagc 780

gattcagatt ccgatagcga ttcagattcc gacagtgact cagattccga tagtgactcg 840

gattcagcga gtgattcaga ttcagatagc gattcagaat cagatagtga ctcagactca 900

gacagtgatt cagattcaga tagtgactca gactcagaca gcgattcaga atcagatagt 960

gactccgatt cagacagcga ttcagaatca gatagtgact ccgattcaga tagcgattcg 1020

gattcagcga gtgattcaga ctcaggtagt gactccgatt catcaagtga ttcagattcc 1080

gattcaacga gtgacacagg atcagacaac gactcagaca gtgattcaaa tagcgattcc 1140

gagtcaggtt ctaacaataa tgtagttccg cctaattcac ctaaaaatgg tactaatgct 1200

tctaataaaa atgaggctaa agatagtaaa gaaccattac cagatacagg ttctgaagat 1260

gaagcgaata cgtcactaat ttggggatta ttagcatcat taggttcatt actacttttc 1320

agaagaaaaa aagaaaataa agataagaaa taa 1353

<210> 82

<211> 935

<212> PRT

<213> 金黄色葡萄球菌

<400> 82

Met Asn Met Lys Lys Lys Glu Lys His Ala Ile Arg Lys Lys Ser Ile

1 5 10 15

Gly Val Ala Ser Val Leu Val Gly Thr Leu Ile Gly Phe Gly Leu Leu

20 25 30

Ser Ser Lys Glu Ala Asp Ala Ser Glu Asn Ser Val Thr Gln Ser Asp

35 40 45

Ser Ala Ser Asn Glu Ser Lys Ser Asn Asp Ser Ser Ser Val Ser Ala

50 55 60

Ala Pro Lys Thr Asp Asp Thr Asn Val Ser Asp Thr Lys Thr Ser Ser

65 70 75 80

Asn Thr Asn Asn Gly Glu Thr Ser Val Ala Gln Asn Pro Ala Gln Gln

85 90 95

Glu Thr Thr Gln Ser Ser Ser Thr Asn Ala Thr Thr Glu Glu Thr Pro

100 105 110

Val Thr Gly Glu Ala Thr Thr Thr Thr Thr Asn Gln Ala Asn Thr Pro

115 120 125

Ala Thr Thr Gln Ser Ser Asn Thr Asn Ala Glu Glu Leu Val Asn Gln

130 135 140

Thr Ser Asn Glu Thr Thr Ser Asn Asp Thr Asn Thr Val Ser Ser Val

145 150 155 160

Asn Ser Pro Gln Asn Ser Thr Asn Ala Glu Asn Val Ser Thr Thr Gln

165 170 175

Asp Thr Ser Thr Glu Ala Thr Pro Ser Asn Asn Glu Ser Ala Pro Gln

180 185 190

Asn Thr Asp Ala Ser Asn Lys Asp Val Val Ser Gln Ala Val Asn Pro

195 200 205

Ser Thr Pro Arg Met Arg Ala Phe Ser Leu Ala Ala Val Ala Ala Asp

210 215 220

Ala Pro Ala Ala Gly Thr Asp Ile Thr Asn Gln Leu Thr Asp Val Lys

225 230 235 240

Val Thr Ile Asp Ser Gly Thr Thr Val Tyr Pro His Gln Ala Gly Tyr

245 250 255

Val Lys Leu Asn Tyr Gly Phe Ser Val Pro Asn Ser Ala Val Lys Gly

260 265 270

Asp Thr Phe Lys Ile Thr Val Pro Lys Glu Leu Asn Leu Asn Gly Val

275 280 285

Thr Ser Thr Ala Lys Val Pro Pro Ile Met Ala Gly Asp Gln Val Leu

290 295 300

Ala Asn Gly Val Ile Asp Ser Asp Gly Asn Val Ile Tyr Thr Phe Thr

305 310 315 320

Asp Tyr Val Asp Asn Lys Glu Asn Val Thr Ala Asn Ile Thr Met Pro

325 330 335

Ala Tyr Ile Asp Pro Glu Asn Val Thr Lys Thr Gly Asn Val Thr Leu

340 345 350

Thr Thr Gly Ile Gly Thr Asn Thr Ala Ser Lys Thr Val Leu Ile Asp

355 360 365

Tyr Glu Lys Tyr Gly Gln Phe His Asn Leu Ser Ile Lys Gly Thr Ile

370 375 380

Asp Gln Ile Asp Lys Thr Asn Asn Thr Tyr Arg Gln Thr Ile Tyr Val

385 390 395 400

Asn Pro Ser Gly Asp Asn Val Val Leu Pro Ala Leu Thr Gly Asn Leu

405 410 415

Ile Pro Asn Thr Lys Ser Asn Ala Leu Ile Asp Ala Lys Asn Thr Asp

420 425 430

Ile Lys Val Tyr Arg Val Asp Asn Ala Asn Asp Leu Ser Glu Ser Tyr

435 440 445

Tyr Val Asn Pro Ser Asp Phe Glu Asp Val Thr Asn Gln Val Arg Ile

450 455 460

Ser Phe Pro Asn Ala Asn Gln Tyr Lys Val Glu Phe Pro Thr Asp Asp

465 470 475 480

Asp Gln Ile Thr Thr Pro Tyr Ile Val Val Val Asn Gly His Ile Asp

485 490 495

Pro Ala Ser Thr Gly Asp Leu Ala Leu Arg Ser Thr Phe Tyr Gly Tyr

500 505 510

Asp Ser Asn Phe Ile Trp Arg Ser Met Ser Trp Asp Asn Glu Val Ala

515 520 525

Phe Asn Asn Gly Ser Gly Ser Gly Asp Gly Ile Asp Lys Pro Val Val

530 535 540

Pro Glu Gln Pro Asp Glu Pro Gly Glu Ile Glu Pro Ile Pro Glu Asp

545 550 555 560

Ser Asp Ser Asp Pro Gly Ser Asp Ser Gly Ser Asp Ser Asn Ser Asp

565 570 575

Ser Gly Ser Asp Ser Gly Ser Asp Ser Thr Ser Asp Ser Gly Ser Asp

580 585 590

Ser Ala Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp Ser Ala Ser Asp

595 600 605

Ser Asp Ser Ala Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp Ser Ala

610 615 620

Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp

625 630 635 640

Ser Ala Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp Ser Ala Ser Asp

645 650 655

Ser Asp Ser Ala Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp Ser Asp

660 665 670

Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp

675 680 685

Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp

690 695 700

Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp

705 710 715 720

Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp

725 730 735

Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp

740 745 750

Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Ala

755 760 765

Ser Asp Ser Asp Ser Asp Ser Asp Ser Glu Ser Asp Ser Asp Ser Asp

770 775 780

Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp

785 790 795 800

Ser Glu Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Glu Ser Asp

805 810 815

Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp

820 825 830

Ser Gly Ser Asp Ser Asp Ser Ser Ser Asp Ser Asp Ser Asp Ser Thr

835 840 845

Ser Asp Thr Gly Ser Asp Asn Asp Ser Asp Ser Asp Ser Asn Ser Asp

850 855 860

Ser Glu Ser Gly Ser Asn Asn Asn Val Val Pro Pro Asn Ser Pro Lys

865 870 875 880

Asn Gly Thr Asn Ala Ser Asn Lys Asn Glu Ala Lys Asp Ser Lys Glu

885 890 895

Pro Leu Pro Asp Thr Gly Ser Glu Asp Glu Ala Asn Thr Ser Leu Ile

900 905 910

Trp Gly Leu Leu Ala Ser Leu Gly Ser Leu Leu Leu Phe Arg Arg Lys

915 920 925

Lys Glu Asn Lys Asp Lys Lys

930 935

<210> 83

<211> 545

<212> PRT

<213> 人工序列

<220>

<223> ClfA -部分的克隆的肽序列

<400> 83

Glu Asn Ser Val Thr Gln Ser Asp Ser Ala Ser Asn Glu Ser Lys Ser

1 5 10 15

Asn Asp Ser Ser Ser Val Ser Ala Ala Pro Lys Thr Asp Asp Thr Asn

20 25 30

Val Ser Asp Thr Lys Thr Ser Ser Asn Thr Asn Asn Gly Glu Thr Ser

35 40 45

Val Ala Gln Asn Pro Ala Gln Gln Glu Thr Thr Gln Ser Ser Ser Thr

50 55 60

Asn Ala Thr Thr Glu Glu Thr Pro Val Thr Gly Glu Ala Thr Thr Thr

65 70 75 80

Thr Thr Asn Gln Ala Asn Thr Pro Ala Thr Thr Gln Ser Ser Asn Thr

85 90 95

Asn Ala Glu Glu Leu Val Asn Gln Thr Ser Asn Glu Thr Thr Ser Asn

100 105 110

Asp Thr Asn Thr Val Ser Ser Val Asn Ser Pro Gln Asn Ser Thr Asn

115 120 125

Ala Glu Asn Val Ser Thr Thr Gln Asp Thr Ser Thr Glu Ala Thr Pro

130 135 140

Ser Asn Asn Glu Ser Ala Pro Gln Asn Thr Asp Ala Ser Asn Lys Asp

145 150 155 160

Val Val Ser Gln Ala Val Asn Pro Ser Thr Pro Arg Met Arg Ala Phe

165 170 175

Ser Leu Ala Ala Val Ala Ala Asp Ala Pro Ala Ala Gly Thr Asp Ile

180 185 190

Thr Asn Gln Leu Thr Asp Val Lys Val Thr Ile Asp Ser Gly Thr Thr

195 200 205

Val Tyr Pro His Gln Ala Gly Tyr Val Lys Leu Asn Tyr Gly Phe Ser

210 215 220

Val Pro Asn Ser Ala Val Lys Gly Asp Thr Phe Lys Ile Thr Val Pro

225 230 235 240

Lys Glu Leu Asn Leu Asn Gly Val Thr Ser Thr Ala Lys Val Pro Pro

245 250 255

Ile Met Ala Gly Asp Gln Val Leu Ala Asn Gly Val Ile Asp Ser Asp

260 265 270

Gly Asn Val Ile Tyr Thr Phe Thr Asp Tyr Val Asp Asn Lys Glu Asn

275 280 285

Val Thr Ala Asn Ile Thr Met Pro Ala Tyr Ile Asp Pro Glu Asn Val

290 295 300

Thr Lys Thr Gly Asn Val Thr Leu Thr Thr Gly Ile Gly Thr Asn Thr

305 310 315 320

Ala Ser Lys Thr Val Leu Ile Asp Tyr Glu Lys Tyr Gly Gln Phe His

325 330 335

Asn Leu Ser Ile Lys Gly Thr Ile Asp Gln Ile Asp Lys Thr Asn Asn

340 345 350

Thr Tyr Arg Gln Thr Ile Tyr Val Asn Pro Ser Gly Asp Asn Val Val

355 360 365

Leu Pro Ala Leu Thr Gly Asn Leu Ile Pro Asn Thr Lys Ser Asn Ala

370 375 380

Leu Ile Asp Ala Lys Asn Thr Asp Ile Lys Val Tyr Arg Val Asp Asn

385 390 395 400

Ala Asn Asp Leu Ser Glu Ser Tyr Tyr Val Asn Pro Ser Asp Phe Glu

405 410 415

Asp Val Thr Asn Gln Val Arg Ile Ser Phe Pro Asn Ala Asn Gln Tyr

420 425 430

Lys Val Glu Phe Pro Thr Asp Asp Asp Gln Ile Thr Thr Pro Tyr Ile

435 440 445

Val Val Val Asn Gly His Ile Asp Pro Ala Ser Thr Gly Asp Leu Ala

450 455 460

Leu Arg Ser Thr Phe Tyr Gly Tyr Asp Ser Asn Phe Ile Trp Arg Ser

465 470 475 480

Met Ser Trp Asp Asn Glu Val Ala Phe Asn Asn Gly Ser Gly Ser Gly

485 490 495

Asp Gly Ile Asp Lys Pro Val Val Pro Glu Gln Pro Asp Glu Pro Gly

500 505 510

Glu Ile Glu Pro Ile Pro Glu Asp Ser Asp Ser Asp Pro Gly Ser Asp

515 520 525

Ser Gly Ser Asp Ser Asn Ser Asp Ser Gly Ser Asp Ser Gly Ser Asp

530 535 540

Ser

545

<210> 84

<211> 450

<212> PRT

<213> 人工序列

<220>

<223> ClfA -部分的克隆的肽序列

<400> 84

Pro Tyr Ile Val Val Val Asn Gly His Ile Asp Pro Ala Ser Thr Gly

1 5 10 15

Asp Leu Ala Leu Arg Ser Thr Phe Tyr Gly Tyr Asp Ser Asn Phe Ile

20 25 30

Trp Arg Ser Met Ser Trp Asp Asn Glu Val Ala Phe Asn Asn Gly Ser

35 40 45

Gly Ser Gly Asp Gly Ile Asp Lys Pro Val Val Pro Glu Gln Pro Asp

50 55 60

Glu Pro Gly Glu Ile Glu Pro Ile Pro Glu Asp Ser Asp Ser Asp Pro

65 70 75 80

Gly Ser Asp Ser Gly Ser Asp Ser Asn Ser Asp Ser Gly Ser Asp Ser

85 90 95

Gly Ser Asp Ser Thr Ser Asp Ser Gly Ser Asp Ser Ala Ser Asp Ser

100 105 110

Asp Ser Ala Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp Ser Ala Ser

115 120 125

Asp Ser Asp Ser Ala Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp Ser

130 135 140

Ala Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp Ser Ala Ser Asp Ser

145 150 155 160

Asp Ser Ala Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp Ser Ala Ser

165 170 175

Asp Ser Asp Ser Ala Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser

180 185 190

Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser

195 200 205

Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser

210 215 220

Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser

225 230 235 240

Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser

245 250 255

Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser

260 265 270

Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp Ser

275 280 285

Asp Ser Asp Ser Glu Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser

290 295 300

Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Glu Ser Asp Ser

305 310 315 320

Asp Ser Asp Ser Asp Ser Asp Ser Glu Ser Asp Ser Asp Ser Asp Ser

325 330 335

Asp Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp Ser Gly Ser Asp Ser

340 345 350

Asp Ser Ser Ser Asp Ser Asp Ser Asp Ser Thr Ser Asp Thr Gly Ser

355 360 365

Asp Asn Asp Ser Asp Ser Asp Ser Asn Ser Asp Ser Glu Ser Gly Ser

370 375 380

Asn Asn Asn Val Val Pro Pro Asn Ser Pro Lys Asn Gly Thr Asn Ala

385 390 395 400

Ser Asn Lys Asn Glu Ala Lys Asp Ser Lys Glu Pro Leu Pro Asp Thr

405 410 415

Gly Ser Glu Asp Glu Ala Asn Thr Ser Leu Ile Trp Gly Leu Leu Ala

420 425 430

Ser Leu Gly Ser Leu Leu Leu Phe Arg Arg Lys Lys Glu Asn Lys Asp

435 440 445

Lys Lys

450

<210> 85

<211> 717

<212> DNA

<213> 人工序列

<220>

<223> GFP -克隆的DNA序列

<400> 85

atgagtaaag gagaagaact tttcactgga gttgtcccaa ttcttgttga attagatggt 60

gatgttaatg ggcacaaatt ttctgtcagt ggagagggtg aaggtgatgc aacatacgga 120

aaacttaccc ttaaatttat ttgcactact ggaaaactac ctgttccatg gccaacactt 180

gtcactactt tctcttatgg tgttcaatgc ttttcccgtt atccggatca tatgaaacgg 240

catgactttt tcaagagtgc catgcccgaa ggttatgtac aggaacgcac tatatctttc 300

aaagatgacg ggaactacaa gacgcgtgct gaagtcaagt ttgaaggtga tacccttgtt 360

aatcgtatcg agttaaaagg tattgatttt aaagaagatg gaaacattct cggacacaaa 420

ctcgagtaca actataactc acacaatgta tacatcacgg cagacaaaca aaagaatgga 480

atcaaagcta acttcaaaat tcgccacaac attgaagatg gatccgttca actagcagac 540

cattatcaac aaaatactcc aattggcgat ggccctgtcc ttttaccaga caaccattac 600

ctgtcgacac aatctgccct ttcgaaagat cccaacgaaa agcgtgacca catggtcctt 660

cttgagtttg taactgctgc tgggattaca catggcatgg atgagctcta caaataa 717

<210> 86

<211> 238

<212> PRT

<213> 人工序列

<220>

<223> GFP -克隆的肽序列

<400> 86

Met Ser Lys Gly Glu Glu Leu Phe Thr Gly Val Val Pro Ile Leu Val

1 5 10 15

Glu Leu Asp Gly Asp Val Asn Gly His Lys Phe Ser Val Ser Gly Glu

20 25 30

Gly Glu Gly Asp Ala Thr Tyr Gly Lys Leu Thr Leu Lys Phe Ile Cys

35 40 45

Thr Thr Gly Lys Leu Pro Val Pro Trp Pro Thr Leu Val Thr Thr Phe

50 55 60

Ser Tyr Gly Val Gln Cys Phe Ser Arg Tyr Pro Asp His Met Lys Arg

65 70 75 80

His Asp Phe Phe Lys Ser Ala Met Pro Glu Gly Tyr Val Gln Glu Arg

85 90 95

Thr Ile Ser Phe Lys Asp Asp Gly Asn Tyr Lys Thr Arg Ala Glu Val

100 105 110

Lys Phe Glu Gly Asp Thr Leu Val Asn Arg Ile Glu Leu Lys Gly Ile

115 120 125

Asp Phe Lys Glu Asp Gly Asn Ile Leu Gly His Lys Leu Glu Tyr Asn

130 135 140

Tyr Asn Ser His Asn Val Tyr Ile Thr Ala Asp Lys Gln Lys Asn Gly

145 150 155 160

Ile Lys Ala Asn Phe Lys Ile Arg His Asn Ile Glu Asp Gly Ser Val

165 170 175

Gln Leu Ala Asp His Tyr Gln Gln Asn Thr Pro Ile Gly Asp Gly Pro

180 185 190

Val Leu Leu Pro Asp Asn His Tyr Leu Ser Thr Gln Ser Ala Leu Ser

195 200 205

Lys Asp Pro Asn Glu Lys Arg Asp His Met Val Leu Leu Glu Phe Val

210 215 220

Thr Ala Ala Gly Ile Thr His Gly Met Asp Glu Leu Tyr Lys

225 230 235

Claims (14)

1.一种免疫原性组合物，其包含至少一种金黄色葡萄球菌(Staphylococcus aureus)抗原，其中所述抗原是与SEQ ID NO：8的SdrH样多肽、SEQ ID NO：4的Nuc或SEQ ID NO：12的LukG具有至少80％同一性的多肽。

2.根据权利要求1所述的免疫原性组合物，其包含与SEQ ID NO：8的SdrH样多肽具有至少80％同一性的抗原和与SEQ ID NO：12的LukG具有至少80％同一性的抗原。

3.根据权利要求1或2所述的免疫原性组合物，其中所述组合物包含所述金黄色葡萄球菌抗原中的两种或更多种，其呈单独多肽的形式、或呈一种或多种融合多肽的形式、或呈单独多肽和融合多肽的形式。

4.根据权利要求1至3中任一项所述的免疫原性组合物，进一步包含药学上可接受的赋形剂。

5.权利要求1至4中任一项所述的免疫原性组合物，用作赋予受试者针对金黄色葡萄球菌引起的疾病的保护作用的疫苗的用途。

6.一种免疫治疗组合物，其包含与至少一种权利要求1中限定的抗原选择性结合的多克隆抗体，其中所述抗体促进吞噬细胞对金黄色葡萄球菌的摄取和杀死。

7.根据权利要求6所述的免疫治疗组合物，其进一步包含药学上可接受的赋形剂。

8.权利要求6或7所述的免疫治疗组合物，用于赋予受试者针对由金黄色葡萄球菌引起的疾病的保护作用的被动免疫治疗的用途。

9.根据权利要求5或8所述用途的免疫原性或免疫治疗组合物，其中所述金黄色葡萄球菌是耐甲氧西林的金黄色葡萄球菌(MRSA)或甲氧西林易感的金黄色葡萄球菌(MSSA)。

10.根据权利要求5和权利要求8至9中任一项所述用途的免疫原性或免疫治疗组合物，其中所述受试者具有骨关节装置，优选具有骨关节植入物，更优选具有全关节置换假体。

11.权利要求1至9中任一项所述的免疫原性或免疫治疗组合物，用于与一种或多种对金黄色葡萄球菌感染有效的抗生素联合使用。

12.一种鉴定抗原的体外方法，所述抗原赋予受试者针对金黄色葡萄球菌引起的疾病的保护作用，所述方法包括：

a)将包含金黄色葡萄球菌的溶液与包含针对金黄色葡萄球菌抗原产生的抗体的溶液一起孵育，优选在35℃下孵育1小时，从而获得混合悬浮液，

b)使巨噬细胞与步骤a)的混合悬浮液接触，

c)从巨噬细胞中去除混合悬浮液并添加补充有抗生素的新鲜培养基以杀死细胞外的金黄色葡萄球菌细菌，和

d)评估所述巨噬细胞对金黄色葡萄球菌细菌的内化和杀死，其中当所述抗原诱导对金黄色葡萄球菌的内化和杀死增加时，视为所述抗原赋予了针对金黄色葡萄球菌引起的疾病的保护作用。

13.根据权利要求12所述的方法，其中所述巨噬细胞是永生化巨噬细胞系，优选J774.2细胞系。

14.根据权利要求12或13所述的方法，其中通过将在步骤c)之后3小时的内化在巨噬细胞中的细菌量与在步骤c)之后6小时的内化在巨噬细胞中的细菌量进行比较，以在步骤d)中评估对金黄色葡萄球菌细菌的杀死。

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