CN107073095B - 基于脂多糖缺失的细胞组分的抗鲍氏不动杆菌疫苗 - Google Patents

基于脂多糖缺失的细胞组分的抗鲍氏不动杆菌疫苗 Download PDF

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CN107073095B
CN107073095B CN201580036683.9A CN201580036683A CN107073095B CN 107073095 B CN107073095 B CN 107073095B CN 201580036683 A CN201580036683 A CN 201580036683A CN 107073095 B CN107073095 B CN 107073095B
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迈克尔·詹姆斯·麦康奈尔
梅里特克塞尔·加西亚·金塔尼利亚
玛丽娜·普利多·托莱达诺
玛利亚·皮拉尔·佩雷斯·罗梅罗
杰罗尼莫·帕琼·迪亚兹
胡安·约瑟·英凡特·维诺洛
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Abstract

本发明涉及一种包含来自不动杆菌属的LPS缺失的灭活细胞和/或由其形成的外膜囊泡的组合物,及其在制备用于预防由不动杆菌属生物体引起的疾病的药物,优选是疫苗,中的用途。

Description

基于脂多糖缺失的细胞组分的抗鲍氏不动杆菌疫苗
技术领域
本发明一般涉及药理学和免疫学领域,并且特别地涉及适于预防性治疗由鲍氏不动杆菌(Acinetobacter baumannii)菌株在哺乳动物中引起的感染的疫苗组合物。
背景技术
由多药耐药鲍氏不动杆菌引起的感染的临床重要性提高确保用于预防和治疗由该病原体引起的感染的新方法的发展。在这种背景下,某些患者群体的免疫可有助于降低由该病原体引起的发病率和死亡率。基于灭活的全细菌细胞的抗革兰氏阴性细菌疫苗具有高度免疫原性,并且已经显示出对许多细菌种类产生保护性免疫。然而,由于脂多糖的存在,这些疫苗中高水平的内毒素使它们在人类中的使用复杂化。
鲍氏不动杆菌是在医院环境中具有临床重要性的革兰氏阴性结肠杆菌。这种生物体高度分布在土壤和周围水源中(Baumann,P.1968.J.Bacteriol.96,39-42),并且可以作为院内病原体引起不同类型的感染,例如肺炎、菌血症、脑膜炎和皮肤,软组织感染等(García-Quintanilla et al.,2013.Curr.Pharm.Biotechnol.In press)。这种病原体通常感染接受机械通气的患者和身受烧伤的患者(
Figure GDA0003486413080000011
-Price yWeinstein.2008.N.Engl.J.Med.358,1271-1281)。然而,在社区获得性肺炎的情况下(Hoet al.,2009.Chest.136,1119-1127;Ong et al.,2009.Respirology 14,1200-1205)和在越南、伊拉克、科威特和阿富汗中身受战争相关创伤的军事人员中(Jones et al.,2006.Lancet Infect.Dis.6,317-318;Tong,1972.JAMA 219,1044-1047)也分离出鲍氏不动杆菌。对于医院内感染,与鲍氏不动杆菌感染相关的粗死亡率在35%和70%之间(Vila yPachón,2008.Expert Opin.Pharmacother.9,587-599)。由于鲍氏不动杆菌获得对抗生素的耐药性的能力,多药耐药菌株的数量在前几年显著增加(Tasbakan et al.,2009.Mikrobiyol Bul.43,61-70;Valencia et al.,2009.Infect.ControlHosp.Epidemiol.30:257-263)。这些高耐药性菌株的出现使得由鲍氏不动杆菌引起的感染的临床管理复杂化。在这种背景下,抗鲍氏不动杆菌疫苗的开发可以降低由该病原体引起的发病率和死亡率(Pachón y McConnell,2014.Vaccine,In press)。
已经描述的鲍氏不动杆菌实验疫苗可以分为两大类,由单一纯化抗原组成的疫苗和多组分疫苗。在第一组内,外膜蛋白OmpA(Luo et al.,2012.PLoS One 7,e2944),生物膜相关蛋白Bap(Fattahian et al.,2011.Microb.Pathog.51,402-406),膜转运蛋白Ata(Bentancor et al.,2012.Infect.Immun.80,3381-3388)和表面多糖聚-N-乙酰基-β-(1-6)-葡萄糖胺(Bentancor et al.,2012.Infect Immun 80,651-656)由于其引发特异性免疫应答的能力而被描述为良好的候选者。然而,主动免疫后测试存活实验仅证明OmpA提供部分保护,并且在没有形成生物膜的菌株中没有清楚地证明Bap的表达。使用多组分疫苗的方法包括外膜复合物(McConnell et al.,2011.Infect.Immun.79,518-526),外膜囊泡(outer membrane vesicles;McConnell et al.,2011.Vaccine 29,5705-5710)和灭活的全细胞(McConnell y Pachón,2010.Vaccine 29:1-5)。这些疫苗中的每一种诱导强免疫应答,并且能够在使用ATCC 19606菌株和临床分离物的小鼠模型中引发高水平抗感染保护。然而,尽管这些结果给人以希望,鉴于这些疫苗中高含量的内毒素(因这些制剂中存在大量的脂多糖(LPS)),这些疫苗在人类中的使用是复杂的。
LPS由O抗原、核心多糖和类脂A形成,类脂A负责LPS的内毒素活性。使用大肠杆菌的第一研究证明LPS的产生对细菌活力是必需的(Raetz,1990.Annu.Rev Biochem.59,129-170)。然而,随后的工作表明,某些细菌物种,比如脑膜炎奈瑟氏菌和卡他莫拉菌(Neisseria meningitidis y Moraxella catarrhalis),在编码参与LPS生物合成的酶的基因突变后是活的,导致菌株完全缺失LPS(Peng et al.,2005.Infect.Immun.73,7569-7577;Steeghs et al.,1999.Infect.Immun.67,4988-4993)。最近的研究表明鲍氏不动杆菌可以通过参与LPS生物合成的基因lpxA、lpxC和lpxD的突变获得对抗生素粘菌素的耐药性(Moffatt et al.,2010.Antimicrob.Agents Chemother.54,4971-4977),完全缺乏LPS的菌株的存活上升。该结果表明鲍氏不动杆菌在不存在LPS的情况下也可存活,提高了基于这些菌株开发疫苗的可能性。
外膜囊泡(OMV)是由许多革兰氏阴性细菌分泌的来自细菌外膜的囊泡(Kulp etal.,2010.Annu.Rev.Microbiol.64,163-184)。OMV是约20-200nm的球形囊泡,其由外膜蛋白、周质蛋白和LPS组成(Kuehn et al.,2005.Genes Dev.19,2645-2655;Mashburn etal.,2005.Nature.437,422-425)。分泌的OMV已经显示参与群体感应检测,毒力因子转运和基因转移,表明它们在细菌发病机理中起作用。还已经证明,OMV可以通过与脂筏融合将蛋白质递送至宿主细胞内部,表明OMV可以用于大距离运输细菌产物(Kesty et al.,2004.Embo J.23,4538-4549)。Kwon等人最近的研究证明,鲍氏不动杆菌的临床分离物在体外生长期间分泌OMV(Kwon et al.,2009.FEMS Microbiol.Lett.297,150-156)。OMV的蛋白质组学分析证明它们含有多种毒力因子和免疫调节蛋白,这表明OMV在鲍氏不动杆菌的发病机理中起重要作用。
已经开发有基于OMV的疫苗,其用于各种革兰氏阴性细菌,包括脑膜炎奈瑟氏菌、幽门螺杆菌和霍乱弧菌(Bjune et al.,1991.NIPH Ann.14,125-130;Keenan et al.,2003.FEMS Immunol.Med.Microbiol.36,199-205;Bishop et al.,2012.J.Infect.Dis.205,412-21)。用OMV免疫显示会诱导抗多种细菌抗原的抗体,以及在感染的动物模型中提供保护性免疫的能力。此外,分离自脑膜炎奈瑟氏菌血清群B的OMV显示在人类中是安全且致免疫的,并且已经用于控制新西兰脑膜炎球菌性脑膜炎的爆发(Nokleby et al.,2007.Vaccine.25,3080-84)。
由鲍氏不动杆菌引起的感染通常发生在由单个克隆引起的爆发中。为此,如果OMV从致病性克隆中分离,基于OMV的疫苗可能更有效。细菌培养物中OMV的纯化是快速且简单的,仅需要过滤培养物上清液和浓缩OMV。
发明内容
方面A:本发明的该方面涉及适于预防性治疗(感染前)由鲍氏不动杆菌菌株在哺乳动物中引起的感染的药物组合物,优选疫苗组合物,其包括:
a.脂多糖(LPS)缺失的鲍氏不动杆菌菌株全细胞,其特征在于使编码内源性
LPS的一种或多种细胞核酸分子部分或完全失活;和/或
b.来源于上段a)中定义的脂多糖(LPS)缺失的鲍氏不动杆菌菌株的外膜囊泡(OMV)。
在本发明该方面的优选实施例中,脂多糖(LPS)缺失的鲍氏不动杆菌菌株的特征在于选自lpxA、lpxB和/或lpxC的基因的部分或完全失活。
在本发明该方面的另一个优选实施例或其任何优选实施例中,所述药物组合物,优选疫苗组合物,还包含选自以下的多肽,优选重组多肽:
a.氨基酸序列SEQ ID No 27(推定的三价铁铁载体受体(鲍氏不动杆菌ATCC17978;登录号YP_001084684))或其片段,其中术语“片段”在本文中理解为生物活性片段,其选自SEQ ID No 1至SEQ ID NO 11或其任何组合,或与序列SEQ ID NO 1至SEQ ID NO 11中的任一个具有至少85%一致性的氨基酸序列;和/或
b.氨基酸序列SEQ ID No 28(推定的异羟肟酸铁铁载体受体(鲍氏不动杆菌ATCC17978;登录号YP_001084696))或其片段,其中术语片段在本文中理解为生物活性片段,其选自SEQ ID NO 12至SEQ ID NO 23或其任何组合,或与氨基酸SEQ ID NO 12至SEQ ID NO23具有至少85%一致性的序列。
在本发明该方面的另一个优选实施例或其任何优选实施例中,药物组合物,优选疫苗组合物,还包含选自以下的鲍氏不动杆菌的纯化的外膜蛋白序列:SEQ ID NO:29、SEQID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQ ID NO:47、SEQID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51、SEQ ID NO:52、SEQ ID NO:53、SEQID NO:54、SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:57、SEQ ID NO:58、SEQ ID NO:59、SEQID NO:60、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:63、SEQ ID NO:64、SEQ ID NO:65、SEQID NO:66、SEQ ID NO:67、SEQ ID NO:68、SEQ ID NO:69、SEQ ID NO:70、SEQ ID NO:71、SEQID NO:72、SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:77、SEQID NO:78、SEQ ID NO:79、SEQ ID No:80、SEQ ID NO:81、SEQ ID NO:82、SEQ ID NO:83、SEQID NO:84、SEQ ID NO:85、SEQ ID NO:86、SEQ ID NO:87、SEQ ID NO:88、SEQ ID NO:89或其任何组合。
在本发明该方面的另一个优选实施例或其任何优选实施例中,药物组合物,优选疫苗组合物,还包含融合重组多肽序列SEQ ID NO 24和/或25和/或由核苷酸序列SEQ IDNO 26编码的氨基酸序列。
在本发明该方面的另一个优选实施例或其任何优选实施例中,脂多糖(LPS)缺失的鲍氏不动杆菌菌株包含这样的核苷酸序列或用这样的核苷酸序列转化、转导或转染:能够编码在任何前述段落中定义的任何氨基酸序列,使得所述菌株能够产生任何这些氨基酸序列的外源表达。
在本发明该方面的另一个优选实施例或其任何优选实施例中,所述药物组合物,优选疫苗组合物,还包含载体,例如病毒载体、质粒或表达盒,其包含能够编码任何前述段落中定义的任何氨基酸序列的核苷酸序列并表达所述氨基酸序列。
在本发明该方面的另一个优选实施例或其任何优选实施例中,脂多糖(LPS)缺失的鲍氏不动杆菌菌株是灭活的。优选地,所述菌株或细胞来源于ATCC菌株19606。
方面B:本发明的该方面涉及本发明的方面A或其任何优选实施例的药物组合物,优选疫苗组合物,用于预防性治疗或主动免疫由鲍氏不动杆菌在哺乳动物中,优选在人类中引起的感染。
方面C:本发明的该方面涉及包含抗体(单克隆或多克隆)或其片段的疫苗组合物,抗体(单克隆或多克隆)或其片段优选地选自Fab、Fab'、Fab'-SH、Fv、scFv、F(ab')2、Vhh、纳米抗体和双抗体,其对脂多糖(LPS)缺失的鲍氏不动杆菌菌株和/或由其衍生的外膜囊泡(OMV)具有亲和力或结合亲和力。在优选的实施例中,所述抗体或其片段特异性结合脂多糖(LPS)缺失的鲍氏不动杆菌菌株和/或由其衍生的外膜囊泡(OMV)。
“亲和力”或“结合亲和力”KD通常通过测量平衡结合常数(ka)和平衡解离常数(kd)并计算kd与ka的商(KD=kd/ka)来确定。
术语“特异性结合”是指抗体以低于或等于10"6M的亲和力KD(单价亲和力)结合缺乏LPS的菌株或由其衍生的OMV。与其它不相关分子相比,该抗体可以对靶抗原具有明显更大的亲和力抗体。与同源物相比,该抗体对靶抗原具有明显更大的亲和力,例如至少1.5倍、2倍、5倍、10倍、100倍、10"3倍、10"4倍、10"5倍、10"6倍或对靶抗原具有更大的相对亲和力。这种亲和力可以使用常规技术轻易地确定,例如,通过平衡透析、通过使用放射性标记的靶抗原的放射免疫测定法,或本领域技术人员知晓的另一方法。亲和力数据可以通过例如[Kaufman RJ,Sharp PA.(1982)Amplification and expression of sequencescotransfected with a modular dihydrofolate reductase complementary dna gene.JMol Biol.159:601-621]中描述的方法进行分析。
术语“抗体”以最广泛的含义使用且包括完全组装的抗体、单克隆抗体、多克隆抗体、多特异性抗体(例如,双特异性抗体)、可结合抗原的抗体片段(例如,Fab'、F'(ab)2、Fv、单链抗体、双抗体)、骆驼抗体和包含前述抗体的重组肽,只要它们显示出所需的生物活性。
因此,抗体/免疫球蛋白的“功能片段”或“抗原结合抗体片段”定义为保留抗原结合区的抗体/免疫球蛋白片段(例如,IgG的可变区)。抗体的“抗原结合区”通常见于抗体的一个或多个高变区,即CDR-1、CDR-2和/或CDR-3区;然而,可变“框架”区也可以在抗原结合中起重要作用,例如通过为CDR提供支架。
术语“高变区”是指负责抗原结合的抗体或功能片段的可变结构域VH和VL的氨基酸残基。抗体片段的非限制性实例包括Fab、Fab'、F(ab')2、Fv,结构域抗体(dAb)、互补决定区(CDR)片段、单链抗体(scFv)、单链抗体片段、双抗体、三链抗体(triabodies)、四链抗体(tetrabodies)、微型抗体(minibodies)、,线性抗体[J Johnson G,Wu TT.(2000)Kabatdatabase and its applications:30years after the first variabilityplot.Nucleic Acids Res.28:214-218];螯合重组抗体、三体或双体、胞内抗体、纳米抗体、小模块免疫药物(SMI Ps)、抗原结合结构域免疫球蛋白融合蛋白、骆驼化抗体、含VHH的抗体,或突变蛋白或其衍生物,和含至少一部分免疫球蛋白(足以使特异性抗原结合至多肽)的多肽,例如CDR序列,只要该抗体保留所需的生物活性;以及由抗体片段形成的多特异性抗体[Chothia C,Lesk AM.(1987)Canonical structures for the hypervariableregions of immunoglobulins.J Mol Biol.196:901-917;Zapata G,Ridgway JB,Mordenti J,Osaka G,Wong WL,Bennett GL,Carter P.(1995)Engineering linear F(ab')2fragments for efficient production in Escherichia coli and enhancedantiproliferative activity.Protein Eng.8:1057-1062]。
在本发明方面C的优选实施例中,药物或疫苗组合物是用如本发明第一方面定义的疫苗组合物免疫哺乳动物后获得的或可获得的。
方面D:本发明的该方面涉及如本发明的方面C中所定义的疫苗组合物,其用于治疗性处理(感染后),或用于由鲍氏不动杆菌在哺乳动物,优选在人中,引起的感染的被动免疫。方面E:本发明的该方面涉及脂多糖(LPS)缺失的鲍氏不动杆菌菌株,该脂多糖(LPS)缺失的鲍氏不动杆菌菌株用能够编码如本发明方面A中所定义的任何氨基酸序列的核苷酸序列转化,转导或转染,使得这种菌株能够产生任何所述氨基酸序列的外源表达。优选地,所述鲍氏不动杆菌缺陷菌株用作药物。
方面F:本发明的该方面涉及生产抗体或其片段的方法,所述抗体或其片段优选地选自Fab、Fab'、Fab'-SH、Fv、scFv、F(ab')2、Vhh、纳米抗体和双抗体,所述方法包括:
a.选择抗体或其片段,优选地选自抗体库;
b.使用脂多糖(LPS)缺失的鲍氏不动杆菌菌株和/或由其衍生的外膜囊泡(OMV)作为抗原靶;
c.选择具有亲和力或结合亲和力或能够特异性结合这种菌株和/或OMV的那些抗体或其片段;并且
d.生产在上述步骤c)中鉴定的那些抗体或其片段
应当注意,鲍氏不动杆菌中的血清型特异性变异依赖于LPS组分的表位的变化。通过根据上述方面F中详述的方法消除LPS组分,我们使抗体集中提升至针对与LPS组分无关的细菌表面变异较少的表位的抗体。这些表位在鲍氏不动杆菌菌株或属于鲍氏不动杆菌分类中使用的所有鲍氏不动杆菌国际克隆的个体分离物中是保守的。因此,该方法提供了用于抗鲍氏不动杆菌感染的普及治疗的工具,其与造成宿主感染的菌株的来源无关。
方面G:本发明的该方面涉及通过本发明方面F的方法产生,获得或可获得的抗体或其片段。方面H:本发明的该方面涉及脂多糖(LPS)缺失和/或由其衍生的外膜囊泡(OMV)的鲍氏不动杆菌菌株用于生产具有亲和力或结合亲和力,或能够特异性结合这种菌株和/或OMV,的抗体或其片段的用途。
发明的具体描述
本发明涉及由鲍氏不动杆菌(A.baumannii)的LPS缺失的全细胞和/或外膜囊泡组成的组合物和疫苗,所述组合物和疫苗能够抗由感染性病原体引起的感染提供保护。
发明人证明,LPS缺失的鲍氏不动杆菌灭活细胞和/或来自鲍氏不动杆菌的外膜囊泡在接种后产生免疫,这为抗由所述细菌引起的后感染提供了保护,证明了这些细胞或菌株作为抗鲍氏不动杆菌引起的感染的预防性疫苗的效用。
本发明的第一方面涉及一种在LPS缺失的鲍氏不动杆菌细胞或菌株,下文称为本发明的细胞或菌株。
不动杆菌的种类是严格好氧的非发酵和氧化酶阴性非运动杆菌,并在显微镜中成对出现。它们在自然界中广泛分布,并且在土壤中是重要的且有助于土壤的矿化。
应当理解,本发明中的“灭活细胞”是不具有复制能力但保持其免疫原性能力的细胞。本发明的细胞在接种之前被灭活以防止它们在宿主中复制,并因此阻止通过其施用产生的发明。本发明的细胞的灭活可以使用现有技术中已知的各种方法进行,例如但不限于:吸附、加热、紫外光、电离辐射、超声、苯酚、甲醛、甲醛、结晶紫、甘油醛、环氧乙烷、丙内酯、乙烯胺(ethylenamina)、溴乙烯胺(bromoethyleneamina)或福尔马林。在优选的实施例中,本发明的细胞用福尔马林灭活。在另一个优选的实施例中,本发明的细胞来自鲍氏不动杆菌并且它们用福尔马林灭活。
在本发明的该方面的一个优选实施例中,LPS缺陷可以通过使编码LPS亚基(特别是LPS的lpxA、lpxB和/或lpxC)的内源基因的一种或多种细胞核酸分子部分或全部失活而实现。
在本发明的另一个优选实施例中,通过在编码参与LPS生物合成的基因的核酸序列和/或控制其表达的序列中缺失和/或插入一个或多个核苷酸而获得LPS缺失的不动杆菌细胞或菌株。缺失和/或插入可以通过同源重组、插入转座子或本领域已知的其它适当方法产生。
在本发明的优选实施例中,通过,例如,构建含有基因lpxA,lpxB,lpxC,lpxD,lpxK,lpxL和/或lpxM或其任何组合的自杀载体,或者以筛选用标记基因打断,用载体转化靶细胞并且筛选LPS表达阴性的阳性细胞,从而使所述序列失活。
在本发明的另一个优选实施例中,本发明的细胞或菌株优选为鲍氏不动杆菌细胞,特别是减毒的鲍氏不动杆菌细胞或其它不动杆菌、贝氏不动杆菌(Acinetobacterbaylyi)、拜叶林克氏不动杆菌(A.beijerinckii)、A.bereziniae、A.boissieri、波氏不动杆菌(A.bouvetii)、A.brisouii、碳酸钙不动杆菌(A.calcoaceticus)、金氏不动杆菌(A.gerneri)、A.guillouiae、格氏不动杆菌(A.grimontii)、A.gyllenbergii、溶血不动杆菌(A.haemolyticus)、A.indicus、约翰逊不动杆菌(A.johnsonii)、琼氏不动杆菌(A.junii)、洛菲不动杆菌(A.lwoffii)、A.nectaris、医院不动杆菌(A.nosocomialis)、小茵落不动杆菌(A.parvus)、皮特不动杆菌(A.pittii)、A.puyangensis、抗辐射不动杆菌(A.radioresistens)、A.rudis、信氏不动杆菌(A.schindleri)、A.soli、坦氏不动杆菌(A.tandoii)、腾氏不动杆菌(A.tjernbergiae)、唐氏不动杆菌(A.towneri)、乌氏不动杆菌(A.ursingii)或威尼斯不动杆菌(A.venetianus)。
在本报告中,应当理解,不动杆菌是指细菌界,变形菌门,γ变形菌纲,假单胞菌目,莫拉氏菌科。
应当理解,本发明中的“鲍氏不动杆菌的细胞或菌株”是属于细菌界,变形菌门,γ变形菌纲,假单胞菌目,莫拉氏菌科,不动杆菌属,鲍氏不动杆菌种的那些细胞。
应当理解,“脂多糖(LPS)或脂寡糖”是在各种革兰氏阴性菌的外膜上发现的组分。由于其发现史,术语LPS通常和“内毒素”可互换使用。LPS由多糖链组成,其余是脂质,称为脂质A,其是形成内毒素活性的原因。多糖链在不同细菌之间是可变的并且决定血清型。内毒素的大小约为10kDa,但可形成高达1000kDa的大聚集体。人类能够生产针对LPS的抗体,但是通常这些抗体只能防御特定血清型的细菌。内毒素是形成由革兰氏阴性菌如脑膜炎奈瑟氏菌和鲍氏不动杆菌引起的感染的许多临床表现的原因。
本发明的组合物
本发明的第二方面涉及一种组合物,下文成为本发明的组合物,其包括:
a)本发明的细胞或菌株,以及
b)任选地,核苷酸和/或氨基酸或多肽序列。
在本发明该方面的更优选的实施例中,核酸和/或氨基酸序列或多肽是重组的。
在另一个更优选的实施例中,所述多肽选自
I)肽序列SEQ ID NO.27(推定的三价铁载体受体(鲍氏不动杆菌ATCC 17978;登录号YP_001084684))或其片段,其中所述片段是生物活性片段,优选地选自SEQ ID NO:
1至SEQ ID NO.11或其任何组合,或与肽序列SEQ ID NO.1至SEQ ID NO.11具有至少85%序列一致性的序列,和/或
II)肽序列SEQ ID No 28(推定的异羟肟酸铁铁载体受体(鲍氏不动杆菌ATCC17978;登录号YP_001084696))或其片段,其中所述片段是生物活性片段,优选地选自SEQID NO:12至SEQ ID NO.23或其任何组合,或与肽序列SEQ ID NO.12至SEQ ID NO.23具有至少85%序列一致性的序列。
在另一个更优选的实施例中,本发明的组合物包含氨基酸序列SEQ ID NO.28和氨基酸序列SEQ ID NO.27。
在另一个优选的实施例中,本发明的组合物包含由选自SEQ ID NO:1至SEQ IDNO:23或者与序列SEQ ID NO:1至SEQ ID NO:23具有至少85%一致性的这些序列的变体的至少2个,优选3个,更优选4个氨基酸序列组成的融合蛋白。
在另一个优选的实施例中,融合蛋白包含氨基酸序列SEQ ID NO:24或氨基酸序列SEQ ID NO:25。
在另一个优选的实施例中,本发明的组合物包含能够转录本发明中所述氨基酸序列的核苷酸序列,下文称为本发明的核苷酸序列。更优选地,核苷酸序列为SEQ ID NO:26。
前述片段在氨基酸序列上至少有一个氨基酸不同。最优选的变体是与SEQ ID NO:1至SEQ ID NO:25中所示的任何多肽具有至少85%或更多,包括90%,93%或更多,并且优选95%或更多,96%或更多,97%或更多,98%或更多,99%或更多序列一致性的那些变体。更优选地,本发明涉及通过与多肽SEQ ID NO:1至SEQ ID NO:25中任一个相关的至少一个(至少两个,至少三个,至少四个)突变表征的序列变体。与发明内容部分中描述的发明一致,突变可以指通过插入、缺失和取代选择的任何突变。优选取代。
在另一个优选的实施例中,本发明的组合物包含表达载体(下文称为本发明的表达载体),其包含本发明的核苷酸序列。
在另一个优选的实施例中,本发明的组合物还包含LPS缺失的外膜囊泡,下文称为本发明的外膜囊泡。
在另一个优选的实施例中,本发明的组合物还包含从鲍氏不动杆菌的膜纯化的具有氨基酸序列SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ IDNO:45、SEQ ID NO:46;SEQ ID NO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ IDNO:51、SEQ ID NO:52、SEQ ID NO:53、SEQ ID NO:54、SEQ ID NO:55、SEQ ID NO:56、SEQ IDNO:57、SEQ ID NO:58、SEQ ID NO:59、SEQ ID NO:60、SEQ ID NO:61、SEQ ID NO:62、SEQ IDNO:63、SEQ ID NO:64、SEQ ID NO:65、SEQ ID NO:66、SEQ ID NO:67、SEQ ID NO:68、SEQ IDNO:69、SEQ ID NO:70、SEQ ID NO:71、SEQ ID NO:72、SEQ ID NO:73、SEQ ID NO:74、SEQ IDNO:75、SEQ ID NO:76、SEQ ID NO:77、SEQ ID NO:78、SEQ ID NO:79、SEQ ID NO:80、SEQ IDNO:81、SEQ ID NO:82、SEQ ID NO:83、SEQ ID NO:84、SEQ ID NO:85、SEQ ID NO:86、SEQ IDNO:87、SEQ ID NO:88,和SEQ ID NO:89或其任何组合的至少一种或蛋白。
更优选地,鲍氏不动杆菌外膜的至少一种蛋白质通过包括以下步骤的方法获得:
a.用含鲍氏不动杆菌ATCC 19606的菌落接种一升Mueller-Hinton肉汤;
b.孵育培养物直到600nm光密度为0.6;
c.用30ml 10mM磷酸盐缓冲液pH7.2洗涤细菌细胞;
d.以6000×g离心10分钟;
e.将细菌沉淀重悬在pH为7.2的10ml 10mM磷酸盐缓冲液中,通过超声处理5次持续1分钟进行裂解;
f.通过以6000xg离心5分钟除去未裂解的细胞;
g.以4℃,20000×g将上清液离心1小时;
h.通过将5ml 2%的N-月桂酰肌氨酸盐溶解在pH7.2的10mM磷酸盐缓冲液中在37℃下持续30分钟,除去外膜的蛋白质;
i.通过在4℃下以20000×g离心1小时沉淀不溶性部分(含有外膜蛋白质);
j.用pH 6.8的2ml 62.5mM Tric-HCl洗涤沉淀一次,并在4℃下离心1小时;
k.将沉淀重悬在5%SDS溶液中,用甲醇/氯仿沉淀;并且
l.在无菌PBS中重悬沉淀。
在本发明的另一个优选实施例中,本发明的组合物是药物组合物,更优选还包含可接受的药物载体,甚至更优选还包含另一种活性成分。
在另一个优选的实施例中,本发明的组合物还包含佐剂。在另一个优选的实施例中,本发明的组合物为疫苗。
在本发明的上下文中,术语“疫苗”是指用于诱导对疾病的免疫应答的抗原制剂。疫苗由抗原制备,所述抗原一旦在宿主内,通过产生抗体激发免疫应答,并产生免疫记忆,从而产生瞬时或永久免疫。应注意,本文所用的术语“疫苗”还可理解为来自适于由不动杆菌菌株,特别是鲍氏不动杆菌菌株引起的感染的治疗性处理或被动免疫的抗体或其片段的制剂。
核苷酸序列和表达载体
本发明的第三方面涉及核苷酸序列,下文称为本发明的第二核苷酸序列,其编码SEQ ID NO 1至25、27或28中的任一个或其任何组合。本发明的所述第二核苷酸序列还包括核酸序列SEQ ID NO:26。
本发明的第四方面涉及包含本发明的第二核苷酸序列的表达载体,以下称为本发明的表达载体。
在该方面的优选实施例中,本发明的细胞包含本发明的表达载体。
核酸可以位于重组载体中。优选地,重组载体为原核载体,即,含有用于复制和/或整合到原核细胞的基因组中的元件的载体。优选地,重组载体含有可操作地连接表达控制序列的本发明的核酸分子。控制序列优选控制不动杆菌,特别是鲍氏不动杆菌中的活性表达的序列。载体可以是足以整合入染色体的染色体外的载体。本领域的专家已知这样的载体的实例,例如在Sambrook等人的上述文献中所述。
本发明的外膜囊泡
本发明的第五方面涉及LPS缺失的外膜囊泡。在该方面的优选实施例中,外膜囊泡自本发明的细胞或菌株获得。
细胞、囊泡和本发明组合物的用途
第六方面涉及用作药物的本发明的组合物,或者可替换地,涉及本发明的组合物在药物制备上的用途。
本报告中使用的术语“药物”或“药物组合物”是指用于预防、缓解、治疗或治愈人或动物疾病的任何物质。在本发明的上下文中是指包含本发明的组分的组合物。本发明的此组合物包含治疗有效量的不动杆菌属的灭活细胞和/或其外膜囊泡,其能够在针对不动杆菌属而施用该灭活细胞和/或其外膜囊泡的生物体中诱导免疫应答。因此,术语“药物”或“药物组合物”被称为疫苗。
用于获得有效治疗量的剂量取决于多种因素,例如哺乳动物的年龄、体重、性别、耐受性……。本说明书中所使用的“有效治疗量”是指不动杆菌属无活性细胞和/或外膜囊泡产生期望的效果的量,并且通常由期望的治疗效果决定。
本发明的第七方面涉及本发明的组合物,其用于预防,改善或治疗由鲍氏不动杆菌在哺乳动物中引起的感染,或者可替换地,涉及本发明的组合物在加工用于预防,改善或治疗由鲍氏不动杆菌在哺乳动物中引起的感染的药物的用途。
“由不动杆菌属的生物体引起的疾病”应理解为病理病原来自不动杆菌属或其任何代谢产物的那些疾病。不动杆菌属产生各种病理,例如,但不限于:菌血症、脑膜炎、尿路感染、皮肤和软组织感染、手术部位感染和肺炎。由于这些原因,由不动杆菌属生物体引起的疾病的较优选的形式之一选自菌血症、脑膜炎、尿路感染、皮肤和软组织感染、手术部位感染和肺炎。
本发明的药物和组合物可以单独使用或与用于治疗由来自不动杆菌属生物体引起的疾病的其它药物或组合物组合使用。
本发明的药物和组合物也可以包括药学上可接受的载体或赋形剂。
本发明的药物和组合物可以单独使用或与用于治疗或预防由不动杆菌属生物体引起的疾病的其它药物或组合物组合使用。
术语“赋形剂”指的是这样的物质:有助于吸收本发明的药物的组合物的元素,稳定所述元件,活化或帮助制备药物,从而提供稠度或风味,使其更可口。在不排除本段中所述的其它类型的赋形剂的情况下,赋形剂可以将成分保持在一起,例如,为淀粉、糖、纤维素、甜味剂、着色剂的情况,保护药物的功能,例如,将药物与空气和/或湿气隔离,填充丸子、胶囊或任何其它呈递形式的功能,例如,磷酸二氢钙的情况,促进组分的溶解及其在肠中的吸收的功能。
以与赋形剂相同的方式,载体是在药物中用于将本发明的任何组分稀释至期望体积或重量的物质。药学上可接受的载体是惰性物质或与本发明的任何元素具有相似作用的惰性物质。载体的功能是便于结合其它元件,允许更好地配量和施用并且为药物提供稠度和形式。当呈递形式是液体时,药学上可接受的载体是稀释剂。
可用于本发明组合物中的佐剂和药学上可接受的载体是本领域技术人员已知的那些载体。在本报告中,术语“佐剂”是指本身不造成抗原活性的任何试剂,其可用于刺激免疫系统以增加对疫苗的应答。存在许多佐剂,例如,但不限于:磷酸铝、氢氧化铝、toll样受体激动剂、细胞因子、鲨烯、弗氏不完全佐剂和完全佐剂。在本发明的该方面的优选形式中,佐剂选自磷酸铝、氢氧化铝、toll样受体激动剂、细胞因子、鲨烯、弗氏不完全佐剂和完全佐剂。在本发明的该方面的甚至更优选的形式中,佐剂为磷酸铝。
本文所使用的术语“活性成分”、“活性物质”或“药物活性物质”或“药物活性成分”是指在疾病的诊断、治愈、缓解、治疗或预防中潜在地提供药理活性或其它不同作用或影响人或动物体的结构或功能的任何组分。该术语包括在药物加工中促进化学变化,并且以提供特定活性或效果的相同和修饰形式呈递的的那些组分。
本发明的第八方面涉及针对鲍氏不动杆菌在哺乳动物中引起的感染提供保护的本发明的组合物,或者可替换地,涉及本发明的组合物在加工针对鲍氏不动杆菌在哺乳动物中引起的感染提供保护的药物上的用途。
本发明的另一方面涉及本发明的融合蛋白或肽或本发明的第一或第二方面的组合物或本发明的药物组合物,其可以施用一次或多次,例如两次、三次、四次、五次、六次、七次、八次、九次或十次或更多次。每剂中活性成分的量没有特别限制。
本发明的另一方面涉及组合物,其由能够结合至SEQ ID NO:27或SEQ ID NO:28的抗体或其片或在第二方面中定义的融合蛋白或本发明的融合蛋白段组成,其中优选地所述组合物为药物组合物,优选疫苗,并且其中所述药物组合物用于治疗或预防鲍氏不动杆菌引起的感染。
本发明的第九方面涉及可通过用本发明的第一或第二方面的组合物或用本发明的融合蛋白免疫哺乳动物而获得的抗体或其活性片段,优选地所述抗体或活性片段包括这样的组合物,其中优选所述组合物为药物组合物并且所述药物组合物用作治疗方案,特别是用于治疗由鲍氏不动杆菌引起的感染。
根据本发明制备不动杆菌细胞的方法
本发明的第十方面涉及一种制备如上所述的鲍氏不动杆菌细胞的方法。
不动杆菌
与此方面一致,该方法包括以下步骤:(i)提供LPS缺失的细菌细胞,特别是不动杆菌细胞;(ii)在所述细菌细胞中插入重组核酸分子,所述核酸分子编码的融合肽包括以下结构域(a)多肽的至少一个结构域,其中所述结构域能够在哺乳动物中产生免疫应答,和(b)吞噬溶酶体的逃脱结构域;以及(iii)在适当的条件下培养获得的与步骤(ii)一致的细胞。优选地,获得能够表达所述核酸的细胞。更优选地,该细胞为鲍氏不动杆菌细胞。
与另一方面一致,该方法包括以下步骤:(i)提供LPS缺失的细菌细胞,特别是不动杆菌细胞,(ii)在所述细菌中插入重组核酸分子,所述核酸分子编码用于逃脱吞噬溶酶体的肽或多肽,以及(iii)在适当的条件下培养获得的与步骤(ii)一致的细胞。
如果需要,本发明的方法包括在细菌细胞中插入至少一种重组核酸分子,所述分子编码能够在哺乳动物中产生免疫应答的肽或多肽。
应当理解,本发明中的“感染”是由不动杆菌属任何生物体,优选是鲍氏不动杆菌的任何生物体侵袭或定殖任何宿主组织所产生的病状。
应当理解,本发明中的“软组织”是生物体的所有非骨组织。
本发明中所理解的术语“预防”包括避免损伤的出现,所述损伤的原因是不动杆菌属细胞或其任何衍生物或代谢产物。
报告中的术语“抗原”是指可以诱导抗体形成的分子(通常是蛋白质或多糖)。有许多不同类型的分子可以作为抗原,例如蛋白质、肽、多糖,以及更少见的其它分子例如核酸。
术语“耐药性”是指细菌针对药物产生的任何防御机制。由细菌获得和传播的耐药性的机制是最重要的,并且主要包括:产生灭活抗生素的酶,阻碍药物到达其靶标的修饰的出现和/或靶标本身的改变。一种细菌菌株可以针对一种或多种抗生素产生各种耐药性机制,并且抗生素可以以相同的方式被来自各种细菌物种的不同的机制灭活。
术语“多核苷酸”和“核酸”可互换使用,指任何长度的核苷酸的聚合形式,包括DNA和RNA。
术语“氨基酸序列”、“肽”、“寡肽”、“多肽”和“蛋白质”可互换使用,并且是指可以以化学方法或生物化学方法修饰的任何长度的氨基酸的聚合形式。
在权利要求的描述张,词语“包括”及其变体不意在排除其它技术特征,添加物、组分或步骤。对于本领域的专家来说,本发明的描述和实践部分公开了本发明的其它目的、优点和特征。提供以下实施例和附图作为说明,其并不意在限制本发明。
附图说明
图1.IB010的稳定性和内毒素含量。(A)从ATCC 19606和IB010的三份独立培养物提取基因组DNA,并使用lpxD基因特异引物扩增。对应于约1000Kb的条带与完整的lpxD基因对应,而较快的迁移条带与缺失462个核苷酸的lpxD基因对应。(B)通过鲎变形细胞试验(Limulus Amebocyte Assay)测定的ATCC 19606和IB010的内毒素水平。柱代表三份独立培养物的中值,误差条代表平均值的标准误差。EU:内毒素单位。
图2.使用IB010免疫的抗体应答。在免疫前(第0天)和第一次免疫后第7和21天从ATCC 19606免疫小鼠、IB010免疫小鼠和对照小鼠收集血清样本,并通过ELISA测量抗原特异性总IgG(A)和IgM(B)的水平(n=8只小鼠/组)。在21天测量IgG1(C)和IgG2c(D)水平,在ATCC 19606免疫小鼠、IB010免疫小鼠和对照小鼠中通过ELISA测量血清。在所有图中,盒须图分别表示四分位数范围和范围,水平线表示中值。*与相同时间点对照小鼠中的水平相比,p<0.05,与来自相同实验组的7天样本相比,#p<0.05,与ATCC 19606免疫小鼠中的21天样本相比,
Figure GDA0003486413080000141
图3.免疫对组织细菌负荷的影响。用2.0×106cfu(300x LD50)的ATCC 19606菌株感染免疫小鼠和对照小鼠,并在感染后12小时确定脾细菌负荷(n=8只小鼠/组)。数据点代表来自个体小鼠的细菌负荷,水平线代表来自小鼠组的中值。*与对照小鼠相比,p<0.05。
图4.免疫对感染后促炎细胞因子水平的影响。用2.0x 106cfu(300x LD50)的ATCC19606菌株感染免疫小鼠和对照小鼠,确定IL-1β、TNF-α和IL-6的血清水平(n=8只小鼠/组)。数据点代表来自个体小鼠的细胞因子水平,并且水平线代表来自小鼠组的中值。与对照小鼠相比,*p<0.05,与ATCC 19606免疫小鼠相比,#p<0.05。
图5.免疫对弥散性鲍氏不动杆菌感染的小鼠模型中的存活的影响。用2.25x106cfu(340.9x LD50)的ATCC 19606菌株(A)或1.05x 106cfu(2.18x LD50)的鲍氏不动杆菌临床分离物Ab-154(B)感染免疫小鼠和对照小鼠,在接下来的7天监测存活(n=8只小鼠/组)。*与对照小鼠相比,p<0.05。
图6.没有LPS的鲍氏不动杆菌OMV的蛋白质图谱。在培养24小时、48小时和72小时后菌株ATCC 19606和IB010用于产生OMV。在纯化OMV后,使用布Bradford方法定量蛋白质的量,并在10%聚丙烯酰胺凝胶中用考马斯染色使10mcg蛋白质显现。
图7.2,2-联吡啶、铁螯合剂对OMV的蛋白质图谱的影响。菌株ATCC 19606和IB010用于分析培养24小时后2,2-联吡啶(BIP)对OMV的蛋白质图谱的影响。在ATCC 19606菌株的情况下,使用200mcM的浓度,而在IB010的情况下使用100mcM和150mcM的浓度。纯化OMV后,使用Bradford方法定量蛋白质的量,并在10%聚丙烯酰胺凝胶中用考马斯染色使10mcg的蛋白质显现。
图8.2,2联吡啶、铁螯合剂对OMV的生产的影响。菌株ATCC 19606和IB010用于分析培养24小时后2,2联吡啶(BIP)对OMV的生产的影响。在该图中,在用BIP处理并用Bradford测量浓度后显示OMV的总蛋白质含量。
图9.OMV的可视化。使用1.6%的戊二醛固定从ATCC 19606纯化的OMV,用四氧化锇和铅及铀染色,并通过电子显微镜显现。
图10.纯化的OMV的可视化。使用1.6%的戊二醛固定从IB010纯化的OMV,四氧化锇和铅及铀染色,并通过电子显微镜显现。
图11.不含LPS的OMV的蛋白质图谱。菌株IB010和167R用于生产OMV,并且定量每个样本的蛋白质的量。在10%聚丙烯酰胺凝胶中用考马斯染色使10mcg的蛋白质显现。
本发明的实施例
实施例1
道德声明
涉及使用动物的所有实验由大学医院伦理和实验委员会批准(niversityHospital Virgen del Rocío Committee on Ethics and Experimentation,评估代码:2013PI/296)。在所有实验中,努力使痛苦最小化,并且在实验过程中使用硫喷妥钠使看起来濒死的任何动物立即安乐死。
细菌菌株。鲍氏不动杆菌ATCC19606是一种对抗生素敏感的参照菌株。如先前所述(临床和实验室标准协会2013),通过将ATCC 19606的过夜培养物在含有10mg/l粘菌素的Mueller Hinton琼脂上铺板,获得ATCC 19606的LPS缺陷型衍生物。通过对37℃过夜生长后存在的粘菌素耐药突变体的lpxA、lpxC和lpxD基因进行测序,鉴定在涉及LPS生物合成的基因中有突变的菌株。鉴定了lpxD基因中缺失较大的菌株,并命名为IB010。根据临床和实验室标准协会指南[23],通过肉汤微量稀释来确认对粘菌素的耐药性。使用QCL-1000鲎变形细胞试验(Lonza),根据制造商的说明书测量每种菌株的三份独立培养物的内毒素水平来证实LPS不存在。Ab-154菌株是先前表征的鲍氏不动杆菌临床分离物(Gautom,1997.J.Clin.Microbiol.35,2977-2980)。
疫苗制备和小鼠免疫。基于先前描述的方法(Moffatt et al.,2010.Antimicrob.Agents Chemother.54,4971-4977)制备IWC疫苗(含LPS和LPS缺陷型)。简而言之,ATCC19606和IB010菌株在Mueller-Hinton肉汤中生长至OD600为0.8。在IB010的情况下,向培养物中加入10μg/ml粘菌素。为了证实在IB010生长期间没有发生野生型回复,使ATCC 19606和IB010的三份独立培养物生长,并使用QIAmp DNAMini Kit(Qiagen)从每份培养物中分离基因组DNA。使用lpxD特异性引物5′GCTAATTGGTGAAGGTAGTC 3′和5′GACGAATCGTTTGAATCTGC 3′来从培养物中扩增基因组DNA,以证实在生长后IB010中lpxD缺失的存在。
对于疫苗制备,在磷酸盐缓冲液中彻底洗涤细菌,然后在0.5M福尔马林中在室温下摇动18小时进行灭活。通过在血琼脂上铺板来确认细菌完全灭活。将灭活细胞的浓度调节至1x1010个细胞/ml,并与基于铝的佐剂,Alhydrogel 2%(w/v)(InvivoGen)以1:1(v/v)组合。通过在第0和14天向每只四头肌肌内注射100μl疫苗在6至8周龄的雌性C57BL/6小鼠中进行免疫。对照小鼠类似地注射磷酸盐缓冲液和佐剂的混合物。
鲍氏不动杆菌感染的小鼠模型。将先前由我们小组开发并用于评价抗鲍氏不动杆菌的疫苗的败血症小鼠模型用于表征功效(Batson et al.,1950.J.Exp.Med.91,219-229;Rodríguez-Hernández et al.,2000.J.Antimicrob.Chemother.45,493-501)。在腹膜内灌注接种物后,该模型产生弥散性感染,通常导致在24至48小时内死亡。为了制备接种物,鲍氏不动杆菌菌株在37℃下在Mueller-Hinton肉汤培养中生长18小时,并如先前所述(Moffatt et al.,2010.Antimicrob.Agents Chemother.54,4971-4977;Martin et al.,1998.J.Immunol.Methods 212,187-192)在生理盐水中调节到适当的浓度。通过在血琼脂上铺板确定接种物的细菌浓度。在第21天(第二次免疫后一周)通过腹膜内注射0.5ml细菌悬浮液感染小鼠,并监测存活7天。
脾细菌负荷和血清细胞因子水平。在感染后12小时,在免疫小鼠和对照小鼠中确定感染后细菌负荷。用过量的硫喷妥钠使小鼠安乐死,在从眶后窦收集血液样本后,无菌取出脾脏,称重并在2ml生理盐水中进行匀浆。将系列对数稀释液在血琼脂平板上铺板,以进行细菌定量。使用BD OptEIA小鼠试剂盒(BD Biosciences)在感染后12小时确定小鼠白细胞介素-1β(IL-1β)、肿瘤坏死因子α(TNF-α)和白细胞介素-6(IL-6)的血清水平。
酶联免疫吸附试验(ELISA)。对于间接酶联免疫吸附试验(ELISA),通过在4℃下孵育过夜,用含5x 107个细菌细胞/孔的磷酸盐缓冲液涂布96孔板。如先前所述[28],使用在第0、7和21天收集的血清进行ELISA。针对用于免疫小鼠的菌株测量抗体滴度,并且定义为分光光度计读数比背景孔(不含血清的孔)高至少0.1个单位的稀释度。
统计分析。对独立样本使用Kruskal-Wallis H检验和Mann-Whitney U检验,对相依样本使用Friedmann和Wilcoxon检验,比较抗体滴度、细菌负荷和细胞因子水平。适当时应用Bonferroni校正。使用对数秩检验比较存活数据。所有统计均使用15.0版SPSS软件(SPSS Inc.)进行,p值≤0.05被认为是显著的。
结果
选择LPS缺失的菌株用于疫苗开发。在存在10μg/ml粘菌素的情况下,ATCC 19606的生长导致lpxA、lpxC和lpxD基因突变的许多粘菌素耐药衍生物(数据未显示)。这些菌株之一,IB010,在lpxD(核苷酸104-565)基因中包含462个核苷酸的较大缺失,并被选择在疫苗研究中进一步使用。我们推断,基于该菌株含有较大缺失,与在LPS生物合成基因中包含单个核苷酸变化或较小缺失的菌株相比,该菌株在生长期间不太可能回复为野生型。肉汤微量稀释实验证明ATCC 19606菌株的最小抑制浓度为≤0.25μg/ml,并且对于IB010,最小抑制浓度>128μg/ml。这证明:与前述结果类似,lpxD中的突变可导致对粘菌素的耐药性(Moffatt et al.,2010.Antimicrob.Agents Chemother.54,4971-4977)。为了确保IB010在生长期间的遗传稳定性,来自ATCC 19606和IB010的三份独立培养物的基因组DNA用lpxD特异性引物扩增以证实缺失存在。如图1A所示,从所有IB010培养物扩增后,存在与包含462个核苷酸缺失的IB010的突变lpxD基因的条带,表明没有发生回复。对于ATCC 19606和IB010通过鲎变形细胞试验来表征LPS的表型缺失和内毒素水平的降低,并且证明lpxD基因中的突变导致内毒素水平显著降低至每106个细胞>1EU(图1B)。
对LPS缺失的IWC疫苗的抗体应答。用福尔马林处理ATCC 19606和IB010导致没有活细菌,表明细菌被完全灭活。为了定量通过用灭活的IB010免疫产生的抗体应答,使用从阴性对照小鼠(用PBS和佐剂免疫)和用1x 109个灭活的IB010细胞免疫的小鼠收集的血清,进行间接ELISA。基于我们先前已经显示用这些细胞免疫会诱导强烈的免疫应答并产生抗实验感染的保护性免疫(McConnell y Pachón,2010.Vaccine 29,1-5),作为阳性对照,小鼠组用1x 109个灭活的ATCC 19606细胞免疫。如图2A所示,用灭活的IB010免疫在单次肌内给药后7天,在所有小鼠中引起可检测的抗原特异性总IgG水平,并且在通过第二次施用疫苗进行加强后,这些抗体水平明显提高(p=0.03,Wicoxon试验)。接受施用两次灭活的IB010疫苗的小鼠的总IgG滴度与接受含有灭活的野生型细胞的疫苗的小鼠中的滴度相似(p=0.726Mann Whitney U检验)。对照小鼠在任何点都没有可检测的抗原特异性IgG。相比之下,在单次施用后7天,用灭活的IB010疫苗免疫的小鼠和接受灭活的野生型细胞的小鼠之间的IgM水平相似(p=0.186Mann Whitney U检验),然而在第二次免疫后7天,IB010免疫小鼠中没有可检测的抗原特异性IgM,而用灭活的野生型细胞免疫的所有小鼠都具有可检测的IgM水平(图2B)。
确定21天血清中的IgG亚型IgG1和IgG2c(C57BL/6中的IgG2a同源物)的水平(Martin et al.,1998.J.Immunol.Methods 212:187-192)(图2C和D)。与对照小鼠相比,接受灭活疫苗的两组小鼠都具有显著的IgG1和IgG2c水平(p<0.001;Mann-Whitney U检验)。有趣的是,与ATCC 19606免疫小鼠相比,IB010免疫小鼠中的IgG1滴度明显更高(p=0.003;Mann-Whitney U检验),而IgG2c滴度在这些组之间相似。这些结果表明,Th1和Th2应答均由灭活的IB010疫苗引起,类似于对于灭活的ATCC 19606疫苗先前所显示的应答(McConnelly Pachón,2010.Vaccine 29,1-5)。
免疫对感染后细菌负荷的影响。为了表征疫苗对感染后组织细菌负载的影响,我们使用由我们组先前开发的小鼠模型表征用于预防鲍氏不动杆菌引起的感染的疫苗(McConnell et al.,2011.Infect.Immun.79,518-526;McConnell et al.,2011.Vaccine29:5705-5710;McConnell y Pachón,2010.Vaccine 29,1-5)。该模型快速产生弥散性感染,其中感染后刚1小时就在远端器官中检测到细菌[16]。用2.0x106 cfu(300x LD50)的ATCC 19606菌株感染免疫小鼠和对照小鼠,并且在感染后12小时测定脾脏细菌负荷(图3)。与对照小鼠相比,IB010免疫使脾脏中的细菌数量降低约1000倍(p<0.05;Mann-Whitney U检验)。IB010免疫小鼠中的脾脏细菌负荷与用灭活的ATCC 19606细胞免疫的小鼠中的细菌负荷没有明显差异。
免疫对感染后血清细胞因子水平和存活的影响。为了表征用灭活的LPS缺陷疫苗免疫对细胞因子水平的影响,在感染后12小时从免疫小鼠和对照小鼠收集血清,并确定IL-1β、IL-6和TNF-α的水平(图4)。两组免疫小鼠的所有三种细胞因子水平明显低于对照小鼠的所有三种细胞因子水平(对于IL-1β、IL-6和TNF-α,p=0.003;Mann-Whitney U检验),表明免疫小鼠没有经历与败血性休克的发展相关的促炎细胞因子释放。
在第二次免疫后7天,通过用2.25x 106cfu(340.9x LD50)的ATCC 19606菌株感染免疫小鼠和对照小鼠来测试疫苗功效,并监测存活七天(图5)。用IB010疫苗免疫的所有小鼠都免于攻击,而所有对照小鼠在48小时内死亡(P<0.001;对数秩检验)。如预期,用ATCC19606菌株免疫的所有小鼠都在攻击中存活,类似于先前报道的结果(McConnell et al.,2011.Infect.Immun.79,518-526;McConnell et al.,2011.Vaccine 29:5705-5710;McConnell y Pachón,2010.Vaccine 29,1-5)。为了确定用IB010免疫是否可以保护免于被不相关的菌株进行异源攻击,用1.05x 106cfu(2.18x LD50)以前表征的鲍氏不动杆菌临床分离物Ab-154感染免疫小鼠和对照小鼠[29]。再次,所有免疫小鼠在攻击下存活,而对照小鼠在48小时内死于感染(p<0.001;对数秩检验),表明用IB010免疫可针对异源菌株攻击提供的交叉保护。总之,这些结果提供了关于基于缺乏LPS的全细菌细胞开发用于预防由鲍氏不动杆菌引起的感染的疫苗的重要信息。这些结果还可以提供对基于缺乏LPS的菌株开发用于其它细菌物种的疫苗的可能性的见解。
实施例2
该实施例涉及基于从不含LPS的突变体的所述培养物纯化的OMVS的抗鲍氏不动杆菌的疫苗的开发。
为了实现该目的,菌株ATCC 19606T及其不含LPS的突变体IB010,IB010在我们的实验室中由ATCC 19606T菌株产生,并且包含在基因lpxD的位置103和565之间的462个核苷酸缺失。
在实现所述菌株的OMV的纯化时,使用以下方案:
-使菌株在具有10mcg/ml的粘菌素的血琼脂或MHBII平板上更新,并在37℃下生长过夜。
-液体培养物用于使ATCC 19606或IB010生长。将它们以37℃,180rpm通气培养过夜。
-第二天在MHB中制成50或100ml或1L培养物,并以37℃,通气(180rpm)孵育过夜,
-孵育后,将细胞以4℃,4000rpm离心30分钟。
-接下来,用0.22微米过滤器过滤上清液。
-然后,通过以4℃,以30000rpm超速离心90分钟来沉淀OMV。
最后,将沉淀物重悬浮于PBS中,通过铺板证实不存在活细菌。将OMV存储在-80℃。
(方案改编自McConnell MJ et al.2011Aug 5;29(34):5705-10)
使用先前的方案,对OMV进行了不同的纯化。
-纯化在培养24、48和72小时后产生OMV的菌株ATCC 19606和IB010的OMV。在纯化OMV后,使用Bradford方法定量蛋白质的量,并在10%聚丙烯酰胺凝胶中用考马斯染色使10mcg的蛋白质显现。
此外,在存在和不存在作为铁螯合剂的Bip的情况下,用来自菌株ATCC 19606和IB010的OMV进行纯化,目的是验证螯合剂的存在是否导致与铁代谢相关的蛋白质,例如铁载体受体,的表达增加。在这种情况下,纯化OMV,进行蛋白质定量和丙烯酰胺凝胶的考马斯染色,且通过电子显微镜使OMV显现。
最后,从鲍氏不动杆菌Ab-167的临床分离物的LPS突变体纯化OMV,鲍氏不动杆菌Ab-167在lpxC基因中含有ISAba1插入。将蛋白质定量并通过考马斯染色在丙烯酰胺凝胶上显现。并且通过Bradford和2D Quant试剂盒定量蛋白质。
实施例3.外膜蛋白质的纯化。
鲍氏不动杆菌ATCC19606在1升Mueller-Hinton肉汤中生长至600nm的光密度(OD600)为0.6,将沉淀的细菌重悬于10ml 10mM pH7.2的磷酸盐缓冲液中,并通过声波降解法裂解。通过以4,000x g离心5分钟除去未裂解的细胞,并将上清液以20,000_g离心1小时以沉淀细胞被膜。通过在37℃下孵育30分钟,用5ml的2%N-月桂酰肌氨酸盐选择性地溶解内膜。通过以20,000_g离心1小时使不溶性碎片沉淀,然后用2ml 62.5mM Tris-Cl(pH 6.8)洗涤。
通过使用冷清洗剂洗涤步骤从制剂中提取内毒素,其中将蛋白质重悬于5%SDS中并在4℃下孵育10分钟。随后通过在甲醇氯仿中沉淀来除去SDS和内毒素,并重悬浮于PBS中。
佐剂的添加
将浓度为500mcg/ml的纯化蛋白质与磷酸铝佐剂以1:1比例混合。
条款
1.一种LPS缺失的不动杆菌细胞。
2.根据前面权利要求所述的不动杆菌细胞,其通过使编码内源LPS生物合成基因的一个或多个核酸部分或完全失活而获得。
3.根据前面权利要求所述的不动杆菌细胞,其中所述基因选自lpxA、lpxB和/或lpxC或其任何组合。
4.根据前面权利要求中任一项所述的不动杆菌细胞,其中通过在所述基因的编码序列中缺失和/或插入一个或多个核苷酸而获得所述细胞。
5.根据前面权利要求中任一项所述的不动杆菌细胞,其中所述细胞是减毒的不动杆菌细胞。
6.一种组合物,其包含:
a)根据权利要求1-2中任一项的细胞,和
b)核酸分子,和/或多肽。
7.根据前面权利要求所述的组合物,其中所述核酸分子是重组的,并且所述多肽是重组的。
8.根据权利要求6-7中任一项所述的组合物,其中所述多肽选自:
a)肽序列SEQ ID NO:27(推定的三价铁载体受体(鲍氏不动杆菌ATCC 17978;登录号YP_001084684))或其片段,其中所述片段是生物活性片段,并且优选地选自SEQ ID NO:1至SEQ ID NO:11或其任何组合,或与肽序列SEQ ID NO:1至SEQ ID NO:11具有至少85%序列一致性的序列,和/或
b)肽序列SEQ ID No 28(推定的异羟肟酸铁铁载体受体(鲍氏不动杆菌ATCC17978;登录号YP_001084696))或其片段,其中所述片段是生物活性片段,优选地选自SEQID NO:12至SEQ ID NO:23或其任何组合,或与肽序列SEQ ID NO:12至SEQ ID NO:23具有至少85%序列一致性的序列。
9.根据权利要求6-8中任一项所述的组合物,其还包含氨基酸序列SEQ ID NO:28和氨基酸序列SEQ ID NO:27。
10.根据权利要求6-9中任一项所述的组合物,其还包含融合蛋白,所述融合蛋白包含来自SEQ ID NO:1至SEQ ID NO:23,或与SEQ ID NO:1至SEQ ID NO:23具有至少85%的序列一致性的这些序列的变体的至少2个,优选3个,更优选4个氨基酸序列。
11.根据权利要求10所述的组合物,其中所述融合蛋白还包含氨基酸序列SEQ IDNO:24或氨基酸序列SEQ ID NO:25。
12.根据权利要求6-11中任一项所述的组合物,其中所述组合物包含能够转录根据权利要求8-11中任一项所述的氨基酸序列的核苷酸序列。
13.根据权利要求12所述的组合物,其中所述核苷酸序列为SEQ ID NO:26。
14.根据权利要求6-13中任一项所述的组合物,其还包含表达载体,所述表达载体包含根据权利要求12-13中任一项所述的核苷酸序列
15.根据权利要求6-14中任一项所述的组合物,其还包含LPS缺失的外膜囊泡或根据权利要求1至5中任一项所述的细胞。
16.根据权利要求6-14中任一项所述的组合物,其还包含具有氨基酸序列SEQ IDNO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ IDNO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ IDNO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQ IDNO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51、SEQ ID NO:52、SEQ IDNO:53、SEQ ID NO:54、SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:57、SEQ ID NO:58、SEQ IDNO:59、SEQ ID NO:60、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:63、SEQ ID NO:64、SEQ IDNO:65、SEQ ID NO:66、SEQ ID NO:67、SEQ ID NO:68、SEQ ID NO:69、SEQ ID NO:70、SEQ IDNO:71、SEQ ID NO:72、SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ IDNO:77、SEQ ID NO:78、SEQ ID NO:79、SEQ ID NO:80、SEQ ID NO:81、SEQ ID NO:82、SEQ IDNO:83、SEQ ID NO:84、SEQ ID NO:85、SEQ ID NO:86、SEQ ID NO:87、SEQ ID NO:88、SEQ IDNO:89或其组合的,鲍氏不动杆菌的纯化的至少一种外膜蛋白。
17.一种LPS缺失的外膜囊泡。
18.根据权利要求17所述的外膜囊泡,其从根据权利要求1-5中任一项所述的细胞获得。
19.根据权利要求6-15中任一项所述的组合物,其中所述细胞或所述外膜囊泡设计为生产根据权利要求8-11或16中任一项所述的氨基酸序列和/或包含根据权利要求12-13中任一项所述的核苷酸或核酸。
20.一种核苷酸序列,其能够转录根据权利要求10-11中任一项所述的任何融合蛋白。
21.一种表达载体,其包含根据权利要求12-13中任一项所述的核苷酸或核酸。
22.根据权利要求7至16和19中任一项所述的组合物,所述组合物是药物组合物。
23.根据权利要求22所述的组合物,其还包含药学上可接受的载体。
24.根据权利要求22或23中任一项所述的组合物,其还包含另一种活性成分。
25.根据权利要求22-24中任一项所述的组合物,其还包含佐剂。
26.根据权利要求7至16、19至22和25中任一项所述的组合物,其中所述组合物为疫苗。
27.根据权利要求7至16、19至22和25中任一项所述的组合物,其用作药物。
28.根据权利要求7至16、19至22和25中任一项所述的组合物,其用于预防、改善或治疗由鲍氏不动杆菌在哺乳动物中引起的感染。
29.根据权利要求7至16、19至22和25中任一项所述的组合物,其用于针对鲍氏不动杆菌在哺乳动物中引起的感染提供保护作用。
30.一种抗体或其活性片段,其通过用根据权利要求7至16、19至22和25中任一项所述的组合物免疫哺乳动物获得。
31.根据前面权利要求所述的抗体或其片段,其中所述组合物是药物组合物,并且其中所述组合物用于治疗,特别是用于治疗和预防由鲍氏不动杆菌引起的感染。
附加条款
1.一种LPS缺失的不动杆菌细胞,其通过使编码内源性LPS生物合成基因的一种或多种细胞核酸分子部分或完全失活获得。
2.根据前面权利要求所述的不动杆菌细胞,其中所述基因选自lpxA、lpxB和/或lpxC,或其任何组合。
3.一种组合物,其包含:
a)根据权利要求1-2中任一项所述的细胞,和
b)重组核酸分子,和/或重组多肽。
4.根据权利要求3所述的组合物,其中所述多肽选自:
a)肽序列SEQ ID NO:27(推定的三价铁载体受体(鲍氏不动杆菌ATCC 17978;登录号YP_001084684))或其片段,其中所述片段是生物活性片段,并且优选地选自SEQ ID NO:1至SEQ ID NO:11或其任何组合,或与肽序列SEQ ID NO:1至SEQ ID NO:11具有至少85%序列一致性的序列,和/或
b)肽序列SEQ ID No 28(推定的异羟肟酸铁铁载体受体(鲍氏不动杆菌ATCC17978;登录号YP_001084696))或其片段,其中所述片段是生物活性片段,并且优选地选自SEQ ID NO:12至SEQ ID NO:23或其任何组合,或与肽序列SEQ ID NO:12至SEQ ID NO:23具有至少85%序列一致性的序列。
5.根据权利要求3-4中任一项所述的组合物,其中所述组合物包含能够转录根据权利要求4所述的氨基酸序列的核苷酸序列,优选SEQ ID NO:26。
6.根据权利要求3-5中任一项所述的组合物,还包含LPS缺失的外膜囊泡或根据权利要求1和2中任一项所述的细胞。
7.根据权利要求3-6中任一项所述的组合物,其还包含从鲍氏不动杆菌的外膜纯化的至少一种蛋白质SEQ ID NO:29,SEQ ID NO:30,SEQ ID NO:31,SEQ ID NO:32,SEQ IDNO:33,SEQ ID NO:34,SEQ ID NO:35,SEQ ID NO:36,SEQ ID NO:37,SEQ ID NO:38,SEQ IDNO:39,SEQ ID NO:40,SEQ ID NO:41,SEQ ID NO:42,SEQ ID NO:43,SEQ ID NO:44,SEQ IDNO:45,SEQ ID NO:46;SEQ ID NO:47;SEQ ID NO:48;SEQ ID NO:49;SEQ ID NO:50;SEQ IDNO:51;SEQ ID NO:52;SEQ ID NO:53;SEQ ID NO:54;SEQ ID NO:55;SEQ ID NO:56;SEQ IDNO:57;SEQ ID NO:58;SEQ ID NO:59;SEQ ID NO:60;SEQ ID NO:61;SEQ ID NO:62;SEQ IDNO:63;SEQ ID NO:64;SEQ ID NO:65;SEQ ID NO:66;SEQ ID NO:67;SEQ ID NO:68;SEQ IDNO:69;SEQ ID NO:70;SEQ ID NO:71;SEQ ID NO:72;SEQ ID NO:73;SEQ ID NO:74;SEQ IDNO:75;SEQ ID NO:76,SEQ ID NO:77,SEQ ID NO:78,SEQ ID NO:79,SEQ ID NO:80,SEQ IDNO:81,SEQ ID NO:82,SEQ ID NO:83,SEQ ID NO:84,SEQ ID NO:85,SEQ ID NO:86,SEQ IDNO:87,SEQ ID NO:88,SEQ ID NO:89,或其组合。
8.一种LPS缺失的外膜囊泡。
9.根据权利要求8所述的外膜囊泡,其由根据权利要求1-2中任一项所述的细胞获得。
10.根据权利要求3-7中任一项所述的组合物,其中所述细胞或所述外膜囊泡设计为生产根据权利要求4和7中任一项所述的多肽序列,和/或包含权利要求5所述的核酸序列。
11.根据权利要求3-7和10中任一项所述的组合物,其中所述组合物是药物组合物。
12.根据权利要求3-7、10和11中任一项所述的组合物,其用作药物。
13.根据权利要求3-7、10和11中任一项所述的组合物,其用于预防、改善或治疗由鲍氏不动杆菌在哺乳动物中引起的感染。
14.一种抗体或其活性片段,其通过用根据权利要求3至7、10和11中任一项所述的组合物免疫哺乳动物获得。
15.根据前面权利要求所述的抗体或其活性片段,其中所述组合物为药物组合物,并且其中所述组合物用于治疗,特别是用于治疗和预防由鲍氏不动杆菌引起的感染。
序列表
<110> 安达卢西亚健康服务部
塞维利亚安达卢西亚健康研究管理公共基金会
瓦克斯丁公司
<120> 基于脂多糖缺失的细胞组分的抗鲍氏不动杆菌疫苗
<130> EP-06839
<140> EP14382164.3
<141> 04.07.2014
<160> 101
<170> PatentIn version 3.5
<210> 1
<211> 12
<212> PRT
<213> Acinetobacter baumannii
<220>
<221> PEPTIDE
<222> (1)..(12)
<223> anti-A. baumannii immunogen
<400> 1
Thr Ser Ser Asp Thr Phe Arg Ser Asp Gly Leu Ala
1 5 10
<210> 2
<211> 28
<212> PRT
<213> Acinetobacter baumannii
<220>
<221> PEPTIDE
<222> (1)..(28)
<223> Anti-A. Baumannii immunogen
<400> 2
Thr Ser Arg Gly Ser Gln Phe Asp Gly Asn Gly Asp Arg Ile Ser Leu
1 5 10 15
Ser Pro Trp Gln Gly Ser Thr Met Asp Thr Asp Thr
20 25
<210> 3
<211> 41
<212> PRT
<213> Acinetobacter baumannii
<220>
<221> PEPTIDE
<222> (1)..(41)
<223> Anti-A. Baumannii immunogen
<400> 3
Tyr Lys Lys Gln Asp Thr Asp Tyr Gly Pro Asp Tyr Ser Tyr Leu Pro
1 5 10 15
Thr Thr Ser Lys Ser Asn Asp Ala Thr Thr Pro Thr Tyr Lys Ala Ile
20 25 30
Lys Gly Leu Lys Leu Ser Asn Pro Leu
35 40
<210> 4
<211> 29
<212> PRT
<213> Acinetobacter baumannii
<220>
<221> PEPTIDE
<222> (1)..(29)
<223> Anti-A. Baumannii immunogen
<400> 4
Arg Asn Glu Lys Ser Arg Phe Phe Pro Tyr Gly Leu Ser Asn Lys Ser
1 5 10 15
Val Thr Ser Val Asn Gln Ser Gln Ser Glu Ile Glu Val
20 25
<210> 5
<211> 36
<212> PRT
<213> Acinetobacter baumannii
<220>
<221> PEPTIDE
<222> (1)..(36)
<223> Anti-A. Baumannii immunogen
<400> 5
Glu Lys Asp Lys Gln Phe Val Asp Ile Leu Ala Thr Gln Tyr Pro Tyr
1 5 10 15
Leu Val Tyr Thr Pro Thr Gly Gln Arg Lys Gly Tyr Gly Pro Asn Thr
20 25 30
Glu Ile Gln Asn
35
<210> 6
<211> 28
<212> PRT
<213> Acinetobacter baumannii
<220>
<221> PEPTIDE
<222> (1)..(28)
<223> Anti-A. Baumannii immunogen
<400> 6
Ile Gln Ala Asp Thr Asp Ala Tyr Ile Pro Ser Arg Glu Thr Thr Met
1 5 10 15
Val Pro Ala Gly Ser Thr His Asp Asp Lys Pro Leu
20 25
<210> 7
<211> 27
<212> PRT
<213> Acinetobacter baumannii
<220>
<221> PEPTIDE
<222> (1)..(27)
<223> Anti-A. Baumannii immunogen
<400> 7
Pro Asp Val Gln Arg Met Leu Arg Asp Val Ser Thr Tyr Thr Val Ser
1 5 10 15
Thr Ala Asn Leu Gln Pro Ile Thr Val Asn Ser
20 25
<210> 8
<211> 23
<212> PRT
<213> Acinetobacter baumannii
<220>
<221> PEPTIDE
<222> (1)..(23)
<223> Anti-A. Baumannii immunogen
<400> 8
Asn Thr Ser Asp Lys Thr Val Gln Phe Asn Asn Arg Ala Ala Lys Val
1 5 10 15
Val Asp Thr Asp Gln Arg Val
20
<210> 9
<211> 22
<212> PRT
<213> Acinetobacter baumannii
<220>
<221> PEPTIDE
<222> (1)..(22)
<223> Anti-A. Baumannii immunogen
<400> 9
Thr Arg Gly Gln Tyr Lys Asp Val Ala Asn Lys Trp His Glu Leu Asn
1 5 10 15
Ser Phe Thr Val Ala Pro
20
<210> 10
<211> 36
<212> PRT
<213> Acinetobacter baumannii
<220>
<221> PEPTIDE
<222> (1)..(36)
<223> Anti-A. Baumannii immunogen
<400> 10
Ile Lys Gly Thr Asn Lys Ala Tyr Lys Asp Asp Arg Glu Leu Ala Ala
1 5 10 15
Phe Ala Thr Thr Gln Asp Glu Ala Phe Gln Asn Ala Val Lys Asn Asp
20 25 30
Ala Asn Ser Ala
35
<210> 11
<211> 33
<212> PRT
<213> Acinetobacter baumannii
<220>
<221> PEPTIDE
<222> (1)..(33)
<223> Anti-A. Baumannii immunogen
<400> 11
Tyr Asn Val Trp Asn Arg Gln Tyr Arg Thr Val Phe Ala Gln Gln Ala
1 5 10 15
Ala Val Ser Asn Ala Asn Pro Leu Leu Ala Ile Pro Ala Glu Gly Arg
20 25 30
Thr
<210> 12
<211> 28
<212> PRT
<213> Acinetobacter baumannii
<220>
<221> PEPTIDE
<222> (1)..(28)
<223> Anti-A. Baumannii immunogen
<400> 12
Val Lys Gly Ala Asp Ser Leu Thr Asn Ala Phe Gly Asp Pro Ser Ala
1 5 10 15
Thr Ile Asn Asn Ile Arg Lys Arg Pro Thr Gln Glu
20 25
<210> 13
<211> 28
<212> PRT
<213> Acinetobacter baumannii
<220>
<221> PEPTIDE
<222> (1)..(28)
<223> Anti-A. Baumannii immunogen
<400> 13
Ser Gly Lys Val Arg Gly Arg Ile Met Gly Tyr Glu Gln Thr Gly Asp
1 5 10 15
Ser Tyr Leu Asp Arg Tyr Ser Ala Glu Lys Asn Gly
20 25
<210> 14
<211> 11
<212> PRT
<213> Acinetobacter baumannii
<220>
<221> PEPTIDE
<222> (1)..(11)
<223> Anti-A. Baumannii immunogen
<400> 14
Ser Gln Glu Gln Asn Lys Pro Asn Ala Asn Asn
1 5 10
<210> 15
<211> 15
<212> PRT
<213> Acinetobacter baumannii
<220>
<221> PEPTIDE
<222> (1)..(15)
<223> Anti-A. Baumannii immunogen
<400> 15
Asn Pro Asn Pro Asp Trp Ala His Trp Asp Asn Glu Thr Gln Asn
1 5 10 15
<210> 16
<211> 36
<212> PRT
<213> Acinetobacter baumannii
<220>
<221> PEPTIDE
<222> (1)..(36)
<223> Anti-A. Baumannii immunogen
<400> 16
Leu Asp Thr Lys His Asn Ser Arg Leu Leu Tyr Tyr Tyr Gly Tyr Pro
1 5 10 15
Lys Ala Asp Gly Ser Gly Val Ser Leu Thr Pro Trp Gly Gly Gln Glu
20 25 30
His Gln Glu Lys
35
<210> 17
<211> 50
<212> PRT
<213> Acinetobacter baumannii
<220>
<221> PEPTIDE
<222> (1)..(50)
<223> Anti-A. Baumanii immunogen
<400> 17
Val Arg Asn His Gln Gln Asp Lys Gln Ser Thr Gly Thr Ile Asn Asp
1 5 10 15
Ser Asn Val Ile Lys Ser Thr Thr Thr Asp Trp Ala Ser Trp Thr Pro
20 25 30
Gln Ser Ile Thr Trp Ser Asp Phe Thr Glu Ala Ala Asn Tyr Lys Gln
35 40 45
Asn Ile
50
<210> 18
<211> 20
<212> PRT
<213> Acinetobacter baumannii
<220>
<221> PEPTIDE
<222> (1)..(20)
<223> Anti-A. Baumannii immunogen
<400> 18
Val Gln Ala Glu Ser Lys Gly Glu Ser Tyr Ser Ser Pro Met Ser Tyr
1 5 10 15
Ser Glu Ser Lys
20
<210> 19
<211> 21
<212> PRT
<213> Acinetobacter baumannii
<220>
<221> PEPTIDE
<222> (1)..(21)
<223> Anti-A. Baumannii immunogen
<400> 19
Arg Pro Gln Thr Gly Ile Asp Lys Asp Thr Asn Gln Ala Leu Lys Pro
1 5 10 15
Ile Glu Gly Lys Ser
20
<210> 20
<211> 29
<212> PRT
<213> Acinetobacter baumannii
<220>
<221> PEPTIDE
<222> (1)..(29)
<223> Anti-A. Baumannii immunogen
<400> 20
Thr Glu Gln Asn Asn Tyr Pro Leu Arg Asn Ser Asp Gly Asn Pro Leu
1 5 10 15
Asn Arg Lys Val Pro Thr Ser Asp Leu Glu Ser Gln Gly
20 25
<210> 21
<211> 20
<212> PRT
<213> Acinetobacter baumannii
<220>
<221> PEPTIDE
<222> (1)..(20)
<223> Anti-A. Baumannii immunogen
<400> 21
Ala Gln Phe Ser Ile Lys Asp Thr Lys Asn Gly Gly Glu Ala Arg Thr
1 5 10 15
Tyr Asn Pro Asn
20
<210> 22
<211> 20
<212> PRT
<213> Acinetobacter baumannii
<220>
<221> PEPTIDE
<222> (1)..(20)
<223> Anti-A. Baumannii immunogen
<400> 22
Gln Asp Gly Ile Lys Leu Tyr Asp Ser Asn Val Asn Gly Thr Ile Lys
1 5 10 15
Gln Asp Ala Tyr
20
<210> 23
<211> 20
<212> PRT
<213> Acinetobacter baumannii
<220>
<221> PEPTIDE
<222> (1)..(20)
<223> Anti-A. Baumannii immunogen
<400> 23
Asp Lys Lys Tyr Leu Asn Ser Phe Pro Asp Gly Gln Ala Phe Tyr Gly
1 5 10 15
Ala Pro Ala Asn
20
<210> 24
<211> 586
<212> PRT
<213> Artificial Sequence
<220>
<223> Fusion protein
<220>
<221> PEPTIDE
<222> (1)..(586)
<223> Fusion protein
<400> 24
Val Lys Gly Ala Asp Ser Leu Thr Asn Ala Phe Gly Asp Pro Ser Ala
1 5 10 15
Thr Ile Asn Asn Ile Arg Lys Arg Pro Thr Gln Glu Ser Gln Glu Gln
20 25 30
Asn Lys Pro Asn Ala Asn Asn Asn Pro Asn Pro Asp Trp Ala His Trp
35 40 45
Asp Asn Glu Thr Gln Asn Leu Asp Thr Lys His Asn Ser Arg Leu Leu
50 55 60
Tyr Tyr Tyr Gly Tyr Pro Lys Ala Asp Gly Ser Gly Val Ser Leu Thr
65 70 75 80
Pro Trp Gly Gly Gln Glu His Gln Glu Lys Val Arg Asn His Gln Gln
85 90 95
Asp Lys Gln Ser Thr Gly Thr Ile Asn Asp Ser Asn Val Ile Lys Ser
100 105 110
Thr Thr Thr Asp Trp Ala Ser Trp Thr Pro Gln Ser Ile Thr Trp Ser
115 120 125
Asp Phe Thr Glu Ala Ala Asn Tyr Lys Gln Asn Ile Val Gln Ala Glu
130 135 140
Ser Lys Gly Glu Ser Tyr Ser Ser Pro Met Ser Tyr Ser Glu Ser Lys
145 150 155 160
Arg Pro Gln Thr Gly Ile Asp Lys Asp Thr Asn Gln Ala Leu Lys Pro
165 170 175
Ile Glu Gly Lys Ser Thr Glu Gln Asn Asn Tyr Pro Leu Arg Asn Ser
180 185 190
Asp Gly Asn Pro Leu Asn Arg Lys Val Pro Thr Ser Asp Leu Glu Ser
195 200 205
Gln Gly Ala Gln Phe Ser Ile Lys Asp Thr Lys Asn Gly Gly Glu Ala
210 215 220
Arg Thr Tyr Asn Pro Asn Gln Asp Gly Ile Lys Leu Tyr Asp Ser Asn
225 230 235 240
Val Asn Gly Thr Ile Lys Gln Asp Ala Tyr Asp Lys Lys Tyr Leu Asn
245 250 255
Ser Phe Pro Asp Gly Gln Ala Phe Tyr Gly Ala Pro Ala Asn Thr Ser
260 265 270
Ser Asp Thr Phe Arg Ser Asp Gly Leu Ala Thr Ser Arg Gly Ser Gln
275 280 285
Phe Asp Gly Asn Gly Asp Arg Ile Ser Leu Ser Pro Trp Gln Gly Ser
290 295 300
Thr Met Asp Thr Asp Thr Tyr Lys Asp Lys Gln Asp Thr Asp Tyr Gly
305 310 315 320
Pro Asp Tyr Ser Tyr Leu Pro Thr Thr Ser Lys Ser Asn Asp Ala Thr
325 330 335
Thr Pro Thr Tyr Lys Ala Ile Lys Gly Leu Lys Leu Ser Asn Pro Leu
340 345 350
Arg Asn Glu Lys Ser Arg Phe Phe Pro Tyr Gly Leu Ser Asn Lys Ser
355 360 365
Val Thr Ser Val Asn Gln Ser Gln Ser Glu Ile Glu Val Glu Lys Asp
370 375 380
Lys Gln Phe Val Asp Ile Leu Ala Thr Gln Tyr Pro Tyr Leu Val Tyr
385 390 395 400
Thr Pro Thr Gly Gln Arg Lys Gly Tyr Gly Pro Asn Thr Glu Ile Gln
405 410 415
Asn Ile Gln Ala Asp Thr Asp Ala Tyr Ile Pro Ser Arg Glu Thr Thr
420 425 430
Met Val Pro Ala Gly Ser Thr His Asp Asp Lys Pro Leu Pro Asp Val
435 440 445
Gln Arg Met Leu Arg Asp Val Ser Thr Tyr Thr Val Ser Thr Ala Asn
450 455 460
Leu Gln Pro Ile Thr Val Asn Ser Asn Thr Ser Asp Lys Thr Val Gln
465 470 475 480
Phe Asn Asn Arg Ala Ala Lys Val Val Asp Thr Asp Gln Arg Val Thr
485 490 495
Arg Gly Gln Tyr Lys Asp Val Ala Asn Lys Trp His Glu Leu Asn Ser
500 505 510
Phe Thr Val Ala Pro Ile Lys Gly Thr Asn Lys Ala Tyr Lys Asp Asp
515 520 525
Arg Glu Leu Ala Ala Phe Ala Thr Thr Gln Asp Glu Ala Phe Gln Asn
530 535 540
Ala Val Lys Asn Asp Ala Asn Ser Ala Tyr Asn Val Trp Asn Arg Gln
545 550 555 560
Tyr Arg Thr Val Phe Ala Gln Gln Ala Ala Val Ser Asn Ala Asn Pro
565 570 575
Leu Leu Ala Ile Pro Ala Glu Gly Arg Thr
580 585
<210> 25
<211> 615
<212> PRT
<213> Artificial Sequence
<220>
<223> Fusion protein
<220>
<221> PEPTIDE
<222> (1)..(615)
<223> Fusion protein
<400> 25
Met Ser Gly Lys Val Arg Gly Arg Ile Met Gly Tyr Glu Gln Thr Gly
1 5 10 15
Asp Ser Tyr Leu Asp Arg Tyr Ser Ala Glu Lys Asn Gly Val Lys Gly
20 25 30
Ala Asp Ser Leu Thr Asn Ala Phe Gly Asp Pro Ser Ala Thr Ile Asn
35 40 45
Asn Ile Arg Lys Arg Pro Thr Gln Glu Ser Gln Glu Gln Asn Lys Pro
50 55 60
Asn Ala Asn Asn Asn Pro Asn Pro Asp Trp Ala His Trp Asp Asn Glu
65 70 75 80
Thr Gln Asn Leu Asp Thr Lys His Asn Ser Arg Leu Leu Tyr Tyr Tyr
85 90 95
Gly Tyr Pro Lys Ala Asp Gly Ser Gly Val Ser Leu Thr Pro Trp Gly
100 105 110
Gly Gln Glu His Gln Glu Lys Val Arg Asn His Gln Gln Asp Lys Gln
115 120 125
Ser Thr Gly Thr Ile Asn Asp Ser Asn Val Ile Lys Ser Thr Thr Thr
130 135 140
Asp Trp Ala Ser Trp Thr Pro Gln Ser Ile Thr Trp Ser Asp Phe Thr
145 150 155 160
Glu Ala Ala Asn Tyr Lys Gln Asn Ile Val Gln Ala Glu Ser Lys Gly
165 170 175
Glu Ser Tyr Ser Ser Pro Met Ser Tyr Ser Glu Ser Lys Arg Pro Gln
180 185 190
Thr Gly Ile Asp Lys Asp Thr Asn Gln Ala Leu Lys Pro Ile Glu Gly
195 200 205
Lys Ser Thr Glu Gln Asn Asn Tyr Pro Leu Arg Asn Ser Asp Gly Asn
210 215 220
Pro Leu Asn Arg Lys Val Pro Thr Ser Asp Leu Glu Ser Gln Gly Ala
225 230 235 240
Gln Phe Ser Ile Lys Asp Thr Lys Asn Gly Gly Glu Ala Arg Thr Tyr
245 250 255
Asn Pro Asn Gln Asp Gly Ile Lys Leu Tyr Asp Ser Asn Val Asn Gly
260 265 270
Thr Ile Lys Gln Asp Ala Tyr Asp Lys Lys Tyr Leu Asn Ser Phe Pro
275 280 285
Asp Gly Gln Ala Phe Tyr Gly Ala Pro Ala Asn Thr Ser Ser Asp Thr
290 295 300
Phe Arg Ser Asp Gly Leu Ala Thr Ser Arg Gly Ser Gln Phe Asp Gly
305 310 315 320
Asn Gly Asp Arg Ile Ser Leu Ser Pro Trp Gln Gly Ser Thr Met Asp
325 330 335
Thr Asp Thr Tyr Lys Asp Lys Gln Asp Thr Asp Tyr Gly Pro Asp Tyr
340 345 350
Ser Tyr Leu Pro Thr Thr Ser Lys Ser Asn Asp Ala Thr Thr Pro Thr
355 360 365
Tyr Lys Ala Ile Lys Gly Leu Lys Leu Ser Asn Pro Leu Arg Asn Glu
370 375 380
Lys Ser Arg Phe Phe Pro Tyr Gly Leu Ser Asn Lys Ser Val Thr Ser
385 390 395 400
Val Asn Gln Ser Gln Ser Glu Ile Glu Val Glu Lys Asp Lys Gln Phe
405 410 415
Val Asp Ile Leu Ala Thr Gln Tyr Pro Tyr Leu Val Tyr Thr Pro Thr
420 425 430
Gly Gln Arg Lys Gly Tyr Gly Pro Asn Thr Glu Ile Gln Asn Ile Gln
435 440 445
Ala Asp Thr Asp Ala Tyr Ile Pro Ser Arg Glu Thr Thr Met Val Pro
450 455 460
Ala Gly Ser Thr His Asp Asp Lys Pro Leu Pro Asp Val Gln Arg Met
465 470 475 480
Leu Arg Asp Val Ser Thr Tyr Thr Val Ser Thr Ala Asn Leu Gln Pro
485 490 495
Ile Thr Val Asn Ser Asn Thr Ser Asp Lys Thr Val Gln Phe Asn Asn
500 505 510
Arg Ala Ala Lys Val Val Asp Thr Asp Gln Arg Val Thr Arg Gly Gln
515 520 525
Tyr Lys Asp Val Ala Asn Lys Trp His Glu Leu Asn Ser Phe Thr Val
530 535 540
Ala Pro Ile Lys Gly Thr Asn Lys Ala Tyr Lys Asp Asp Arg Glu Leu
545 550 555 560
Ala Ala Phe Ala Thr Thr Gln Asp Glu Ala Phe Gln Asn Ala Val Lys
565 570 575
Asn Asp Ala Asn Ser Ala Tyr Asn Val Trp Asn Arg Gln Tyr Arg Thr
580 585 590
Val Phe Ala Gln Gln Ala Ala Val Ser Asn Ala Asn Pro Leu Leu Ala
595 600 605
Ile Pro Ala Glu Gly Arg Thr
610 615
<210> 26
<211> 1650
<212> DNA
<213> Artificial Sequence
<220>
<223> Polynucleotide coding for the fusion protein
<220>
<221> misc_feature
<222> (1)..(1650)
<223> Polynucleotide coding for fusion protein
<400> 26
atgtctggta aagttcgtgg tcgtatcatg ggttacgaac agaccggtga ctcttacctg 60
gaccgttact ctgctgaaaa aaacggtgtt aaaggtgctg actctctgac caacgctttc 120
ggtgacccgt ctgctaccat caacaacatc cgtaaacgtc cgacccagga atctcaggaa 180
cagaacaaac cgaacgctaa caacaacccg aacccggact gggctcactg ggacaacgaa 240
acccagaacc tggacaccaa acacaactct cgtctgctgt actactacgg ttacccgaaa 300
gctgacggtt ctggtgtttc tctgaccccg tggggtggtc aggaacacca ggaaaaagtt 360
cgtaaccacc agcaggacaa acagtctacc ggtaccatca acgactctaa cgttatcaaa 420
tctaccacca ccgactgggc ttcttggacc ccgcagtcta tcacctggtc tgacttcacc 480
gaagctgcta actacaaaca gaacatcgtt caggctgaat ctaaaggtga atcttactct 540
tctccgatgt cttactctga atctaaacgt ccgcagaccg gtatcgacaa agacaccaac 600
caggctctga aaccgatcga aggtaaatct accgaacaga acaactaccc gctgcgtaac 660
tctgacggta acccgctgaa ccgtaaagtt ccgacctctg acctggaatc tcagggtgct 720
cagttctcta tcaaagacac caaaaacggt ggtgaagctc gtacctacaa cccgaaccag 780
gacggtatca aactgtacga ctctaacgtt aacggtacca tcaaacagga cgcttacgac 840
aaaaaatacc tgaactcttt cccggacggt caggctttct acggtgctcc ggctaacacc 900
tcttctgaca ccttccgttc tgacggtctg gctacctctc gtggttctca gttcgacggt 960
aacggtgacc gtatctctct gtctccgtgg cagggttcta ccatggacac cgacacctac 1020
aaagacaaac aggacaccga ctacggtccg gactactctt acctgccgac cacctctaaa 1080
tctaacgacg ctaccacccc gacctacaaa gctatcaaag gtctgaaact gtctaacccg 1140
ctgcgtaacg aaaaatctcg tttcttcccg tacggtctgt ctaacaaatc tgttacctct 1200
gttaaccagt ctcagtctga aatcgaagtt gaaaaagaca aacagttcgt tgacatcctg 1260
gctacccagt acccgtacct ggtttacacc ccgaccggtc agcgtaaagg ttacggtccg 1320
aacaccgaaa tccagaacat ccaggctgac accgacgctt acatcccgtc tcgtgaaacc 1380
accatggttc cggctggttc tacccacgac gacaaaccgc tgccggacgt tcagcgtatg 1440
ctgcgtgacg tttctaccta caccgtttct accgctaacc tgcagccgat caccgttaac 1500
tctaacacct ctgacaaaac cgttcagttc aacaaccgtg ctgctaaagt tgttgacacc 1560
gaccagcgtg ttacccgtgg tcagtacaaa gacgttgcta acaaatggca cgaactgaac 1620
tctttcaccg ttgctccgat caaaggtacc 1650
<210> 27
<211> 746
<212> PRT
<213> Acinetobacter baumannii
<220>
<221> PEPTIDE
<222> (1)..(746)
<223> Amino acid sequence of putative ferric siderophore receptor
protein
<400> 27
Met Thr Pro Cys Cys Leu Ala Ile Ser Ala Ile Phe Ala Gln Gln Ala
1 5 10 15
Tyr Ala Glu Thr Val Thr Gln Thr Ala Glu Val Ser Glu Asn Ala Thr
20 25 30
Gln Lys Pro Val Ala Gln Leu Gln Lys Ile Val Val Thr Ala Thr Arg
35 40 45
Thr Pro Lys Asn Ile Ala Glu Ile Ala Gly Thr Val Gln Ser Ile Asp
50 55 60
Gln Lys Gln Ile Ile Gln Gln Ala Thr Ala Gly Arg Lys Val Ala Asp
65 70 75 80
Ile Leu Ala Gln Leu Val Pro Ser Leu Ala Ser Ser Ser Gly Thr Thr
85 90 95
Ser Asn Tyr Gly Gln Thr Met Arg Gly Arg Asn Val Leu Val Met Ile
100 105 110
Asp Gly Val Ser Gln Thr Gly Ser Arg Asp Val Ser Arg Gln Leu Asn
115 120 125
Ser Ile Ser Pro Gly Met Ile Glu Arg Ile Glu Val Ile Ser Gly Ala
130 135 140
Thr Ser Ile Tyr Gly Ser Gly Ala Thr Gly Gly Ile Ile Asn Ile Ile
145 150 155 160
Thr Lys Arg Ala Asp Thr Ser Lys Pro Leu Ser Phe Glu Thr Lys Val
165 170 175
Gly Ile Thr Ser Ser Asp Thr Phe Arg Ser Asp Gly Leu Ala Tyr Glu
180 185 190
Val Gly Gln Ser Val Ser Phe Asn Lys Gly Asn Ile Asp Gly Phe Leu
195 200 205
Gly Ala Asn Phe Thr Ser Arg Gly Ser Gln Phe Asp Gly Asn Gly Asp
210 215 220
Arg Ile Ser Leu Ser Pro Trp Gln Gly Ser Thr Met Asp Thr Asp Thr
225 230 235 240
Ile Asp Val Asn Gly Arg Leu Asn Phe Asn Leu Asn Asp Thr Gln Thr
245 250 255
Leu Ser Phe Gly Ala Gln Tyr Tyr Lys Asp Lys Gln Asp Thr Asp Tyr
260 265 270
Gly Pro Asp Tyr Ser Tyr Leu Pro Thr Thr Ser Lys Ser Asn Asp Ala
275 280 285
Thr Thr Pro Thr Tyr Lys Ala Ile Lys Gly Leu Lys Leu Ser Asn Pro
290 295 300
Leu Phe Thr Glu Arg Tyr Ala Val Asn Ser Gln Tyr Gln Asn Gln Asp
305 310 315 320
Phe Leu Gly Gln Ile Leu Asn Val Glu Ala Tyr Tyr Arg Asn Glu Lys
325 330 335
Ser Arg Phe Phe Pro Tyr Gly Leu Ser Asn Lys Ser Val Thr Ser Val
340 345 350
Asn Gln Ser Gln Ser Glu Ile Glu Val Ala Gly Leu Arg Ser Thr Met
355 360 365
Gln Thr Asp Leu Asn Ile Ala Asn Arg Asp Met Lys Ile Thr Tyr Gly
370 375 380
Leu Asp Tyr Asp Trp Glu Lys Asp Lys Gln Phe Val Asp Ile Leu Ala
385 390 395 400
Thr Gln Tyr Pro Tyr Leu Val Tyr Thr Pro Thr Gly Gln Arg Lys Gly
405 410 415
Tyr Gly Pro Asn Thr Glu Ile Gln Asn Ile Gly Ala Phe Val Gln Ser
420 425 430
Asp Tyr Ala Val Thr Asp Lys Leu Asn Leu Gln Ala Gly Ile Arg Tyr
435 440 445
Gln Tyr Ile Gln Ala Asp Thr Asp Ala Tyr Ile Pro Ser Arg Glu Thr
450 455 460
Thr Met Val Pro Ala Gly Ser Thr His Asp Asp Lys Pro Leu Phe Asn
465 470 475 480
Leu Gly Ala Val Tyr Lys Leu Thr Asp Ala Gln Gln Val Tyr Ala Asn
485 490 495
Phe Ser Gln Gly Phe Ser Phe Pro Asp Val Gln Arg Met Leu Arg Asp
500 505 510
Val Ser Thr Tyr Thr Val Ser Thr Ala Asn Leu Gln Pro Ile Thr Val
515 520 525
Asn Ser Tyr Glu Leu Gly Trp Arg Leu Asn Gln Asp Asp Gly Leu Asn
530 535 540
Leu Gly Leu Thr Gly Phe Tyr Asn Thr Ser Asp Lys Thr Val Gln Phe
545 550 555 560
Asn Asn Arg Ala Ala Lys Val Val Asp Thr Asp Gln Arg Val Tyr Gly
565 570 575
Ala Glu Ala Thr Ile Ser Tyr Pro Phe Met Glu Asn Tyr Lys Val Gly
580 585 590
Gly Thr Leu Gly Tyr Thr Arg Gly Gln Tyr Lys Asp Val Ala Asn Lys
595 600 605
Trp His Glu Leu Asn Ser Phe Thr Val Ala Pro Val Lys Gly Thr Leu
610 615 620
Phe Ala Glu Trp Asp Asn Asn Glu Gly Tyr Gly Val Arg Val Gln Met
625 630 635 640
Gln Ala Ile Lys Gly Thr Asn Lys Ala Tyr Lys Asp Asp Arg Glu Leu
645 650 655
Ala Ala Phe Ala Thr Thr Gln Asp Glu Ala Phe Gln Asn Ala Val Lys
660 665 670
Asn Asp Ala Asn Ser Ala Ala Gln Ile Lys Gly Tyr Thr Thr Met Asp
675 680 685
Val Leu Ala His Phe Pro Ala Trp Lys Gly Arg Val Asp Phe Gly Val
690 695 700
Tyr Asn Val Trp Asn Arg Gln Tyr Arg Thr Val Phe Ala Gln Gln Ala
705 710 715 720
Ala Val Ser Asn Ala Asn Pro Leu Leu Ala Ile Pro Ala Glu Gly Arg
725 730 735
Thr Tyr Gly Leu Ser Tyr Thr Phe Asn Tyr
740 745
<210> 28
<211> 679
<212> PRT
<213> Acinetobacter baumannii
<220>
<221> PEPTIDE
<222> (1)..(679)
<223> Amino acid sequence of putative ferric hydroxamate siderophore
receptor
<400> 28
Met Gln Thr Ile Gln Val Lys Ala Ser Asp Ala Glu Gln Ser Ser Glu
1 5 10 15
Gln Thr Lys Ala Tyr Asn Val Lys Asn Ser Ser Ser Ala Thr Lys Leu
20 25 30
Asn Ile Glu Ala Lys Glu Thr Pro Gln Thr Ile Asn Val Val Thr Arg
35 40 45
Gln Gln Ile Glu Asp Phe Gly Leu Thr Ser Thr Arg Asp Val Leu Arg
50 55 60
Asn Thr Pro Gly Val Thr Val Ser Asn Gln Glu Thr Glu Arg Thr Thr
65 70 75 80
Tyr Met Ala Arg Gly Phe Glu Ile Ser Asn Ile Leu Thr Asp Gly Val
85 90 95
Gly Phe Pro Leu Ser Gly Tyr Asn Tyr Asn Asn Thr Asn Pro Asp Thr
100 105 110
Tyr Phe Tyr Asp Arg Val Glu Val Val Lys Gly Ala Asp Ser Leu Thr
115 120 125
Asn Ala Phe Gly Asp Pro Ser Ala Thr Ile Asn Asn Ile Arg Lys Arg
130 135 140
Pro Thr Gln Glu Phe Gln Ala Ser Asp Gly Val Ser Tyr Gly Ser Trp
145 150 155 160
Asp Thr Gln Arg Tyr Glu Ala Asp Val Ser Gly Ser Ile Leu Pro Ser
165 170 175
Gly Lys Val Arg Gly Arg Ile Met Gly Tyr Glu Gln Thr Gly Asp Ser
180 185 190
Tyr Leu Asp Arg Tyr Ser Ala Glu Lys Asn Gly Phe Ala Gly Ile Val
195 200 205
Glu Ala Asp Leu Thr Asp Ser Thr Leu Leu Thr Ala Gly Tyr Ser Gln
210 215 220
Glu Gln Asn Lys Pro Asn Ala Asn Asn Trp Gly Ala Leu Pro Leu Leu
225 230 235 240
Asp Ala Asn Gly Lys Gln Ile Ser Tyr Asp Arg Ser Tyr Asn Pro Asn
245 250 255
Pro Asp Trp Ala His Trp Asp Asn Glu Thr Gln Asn Ala Phe Val Glu
260 265 270
Leu Lys Gln Lys Leu Asn Asp Gln Trp Asn Ala Lys Leu Thr Tyr Asn
275 280 285
Tyr Leu Asp Thr Lys His Asn Ser Arg Leu Leu Tyr Tyr Tyr Gly Tyr
290 295 300
Pro Lys Ala Asp Gly Ser Gly Val Ser Leu Thr Pro Trp Gly Gly Gln
305 310 315 320
Glu His Gln Glu Lys His Ala Val Asp Phe Asn Leu Glu Gly Thr Tyr
325 330 335
Lys Leu Phe Asn Arg Glu His Glu Ala Thr Leu Gly Tyr Ser Tyr Val
340 345 350
Arg Asn His Gln Gln Asp Lys Gln Ser Thr Gly Thr Ile Asn Asp Ser
355 360 365
Asn Val Ile Lys Ser Thr Thr Thr Asp Trp Ala Ser Trp Thr Pro Gln
370 375 380
Ser Ile Thr Trp Ser Ala Phe Thr Glu Ala Ala Asn Tyr Lys Gln Asn
385 390 395 400
Ile Asn Ser Ile Tyr Ala Ala Thr Arg Leu His Leu Asn Glu Asp Leu
405 410 415
Lys Leu Leu Leu Gly Val Asn Tyr Val Gln Ala Glu Ser Lys Gly Glu
420 425 430
Ser Tyr Ser Ser Pro Met Ser Tyr Ser Glu Ser Lys Val Ser Pro Tyr
435 440 445
Val Gly Leu Thr Tyr Asn Phe Thr Pro Glu Tyr Thr Gly Tyr Met Ser
450 455 460
Tyr Thr Ser Ile Phe Arg Pro Gln Thr Gly Ile Asp Lys Asp Thr Asn
465 470 475 480
Gln Ala Leu Lys Pro Ile Glu Gly Lys Ser Tyr Glu Met Gly Val Lys
485 490 495
Ser Ser Trp Leu Asp Asp Arg Leu Thr Gly Thr Leu Ser Val Phe Lys
500 505 510
Thr Glu Gln Asn Asn Tyr Pro Leu Arg Asn Ser Asp Gly Asn Pro Leu
515 520 525
Asn Arg Lys Val Pro Thr Ser Asp Leu Glu Ser Gln Gly Val Glu Val
530 535 540
Gly Leu Ser Gly Gln Ile Thr Asp Asn Val Asn Leu Ser Leu Gly Tyr
545 550 555 560
Ala Gln Phe Ser Ile Lys Asp Thr Lys Asn Gly Gly Glu Ala Arg Ile
565 570 575
Tyr Asn Pro Asn Gln Thr Leu Asn Leu Leu Thr Thr Tyr Thr Pro Pro
580 585 590
Val Leu Pro Lys Leu Lys Val Gly Ala Gly Leu Gln Trp Gln Asp Gly
595 600 605
Ile Lys Leu Tyr Asp Ser Asn Val Asn Gly Thr Ile Lys Gln Asp Ala
610 615 620
Tyr Ala Leu Val Asn Leu Met Ala Ser Tyr Glu Val Asn Asp His Ile
625 630 635 640
Thr Leu Gln Ala Asn Gly Asn Asn Ile Phe Asp Lys Lys Tyr Leu Asn
645 650 655
Ser Phe Pro Asp Gly Gln Ala Phe Tyr Gly Ala Pro Ala Asn Tyr Thr
660 665 670
Val Ala Val Lys Phe Lys Tyr
675
<210> 29
<211> 829
<212> PRT
<213> Acinetobacter baumannii
<400> 29
Met Pro Leu Ala Leu Val Ser Ala Met Ala Ala Val Gln Gln Ala Tyr
1 5 10 15
Ala Ala Asp Asp Phe Val Val Arg Asp Ile Arg Val Asn Gly Leu Val
20 25 30
Arg Leu Thr Pro Ala Asn Val Tyr Thr Met Leu Pro Ile Asn Ser Gly
35 40 45
Asp Arg Val Asn Glu Pro Met Ile Ala Glu Ala Ile Arg Thr Leu Tyr
50 55 60
Ala Thr Gly Leu Phe Asp Asp Ile Lys Ala Ser Lys Glu Asn Asp Thr
65 70 75 80
Leu Val Phe Asn Val Ile Glu Arg Pro Ile Ile Ser Lys Leu Glu Phe
85 90 95
Lys Gly Asn Lys Leu Ile Pro Lys Glu Ala Leu Glu Gln Gly Leu Lys
100 105 110
Lys Met Gly Ile Ala Glu Gly Glu Val Phe Lys Lys Ser Ala Leu Gln
115 120 125
Thr Ile Glu Thr Glu Leu Glu Gln Gln Tyr Thr Gln Gln Gly Arg Tyr
130 135 140
Asp Ala Asp Val Thr Val Asp Thr Val Ala Arg Pro Asn Asn Arg Val
145 150 155 160
Glu Leu Lys Ile Asn Phe Asn Glu Gly Thr Pro Ala Lys Val Phe Asp
165 170 175
Ile Asn Val Ile Gly Asn Thr Val Phe Lys Asp Ser Glu Ile Lys Gln
180 185 190
Ala Phe Ala Val Lys Glu Ser Gly Trp Ala Ser Val Val Thr Arg Asn
195 200 205
Asp Arg Tyr Ala Arg Glu Lys Met Ala Ala Ser Leu Glu Ala Leu Arg
210 215 220
Ala Met Tyr Leu Asn Lys Gly Tyr Ile Asn Phe Asn Ile Asn Asn Ser
225 230 235 240
Gln Leu Asn Ile Ser Glu Asp Lys Lys His Ile Phe Ile Glu Val Ala
245 250 255
Val Asp Glu Gly Ser Gln Phe Lys Phe Gly Gln Thr Lys Phe Leu Gly
260 265 270
Asp Ala Leu Tyr Lys Pro Glu Glu Leu Gln Ala Leu Lys Ile Tyr Lys
275 280 285
Asp Gly Asp Thr Tyr Ser Gln Glu Lys Val Asn Ala Val Lys Gln Leu
290 295 300
Leu Leu Arg Lys Tyr Gly Asn Ala Gly Tyr Tyr Phe Ala Asp Val Asn
305 310 315 320
Ile Val Pro Gln Ile Asn Asn Glu Thr Gly Val Val Asp Leu Asn Tyr
325 330 335
Tyr Val Asn Pro Gly Gln Gln Val Thr Val Arg Arg Ile Asn Phe Thr
340 345 350
Gly Asn Ser Lys Thr Ser Asp Glu Val Leu Arg Arg Glu Met Arg Gln
355 360 365
Met Glu Gly Ala Leu Ala Ser Asn Glu Lys Ile Asp Leu Ser Lys Val
370 375 380
Arg Leu Glu Arg Thr Gly Phe Phe Lys Thr Val Asp Ile Lys Pro Ala
385 390 395 400
Arg Ile Pro Asn Ser Pro Asp Gln Val Asp Leu Asn Val Asn Val Glu
405 410 415
Glu Gln His Ser Gly Thr Thr Thr Leu Ala Val Gly Tyr Ser Gln Ser
420 425 430
Gly Gly Ile Thr Phe Gln Ala Gly Leu Ser Gln Thr Asn Phe Met Gly
435 440 445
Thr Gly Asn Arg Val Ala Ile Asp Leu Ser Arg Ser Glu Thr Gln Asp
450 455 460
Tyr Tyr Asn Leu Ser Val Thr Asp Pro Tyr Phe Thr Ile Asp Gly Val
465 470 475 480
Ser Arg Gly Tyr Asn Val Tyr Tyr Arg Lys Thr Lys Leu Asn Asp Asp
485 490 495
Tyr Asn Val Asn Asn Tyr Val Thr Asp Ser Phe Gly Gly Ser Leu Ser
500 505 510
Phe Gly Tyr Pro Ile Asp Glu Asn Gln Ser Leu Ser Ala Ser Val Gly
515 520 525
Val Asp Asn Thr Lys Val Thr Thr Gly Ala Phe Val Ser Thr Tyr Val
530 535 540
Arg Asp Tyr Leu Leu Ala Asn Gly Gly Lys Thr Thr Ser Thr Asn Thr
545 550 555 560
Tyr Cys Leu Val Asp Leu Val Gln Asp Pro Gln Thr Gly Leu Tyr Lys
565 570 575
Cys Pro Glu Gly Gln Thr Ser Gln Pro Tyr Gly Asn Ala Phe Glu Gly
580 585 590
Glu Phe Phe Thr Tyr Asn Leu Asn Leu Gly Trp Ser Tyr Asn Thr Leu
595 600 605
Asn Arg Pro Ile Phe Pro Thr Ser Gly Met Ser His Arg Val Gly Leu
610 615 620
Glu Ile Gly Leu Pro Gly Ser Asp Val Asp Tyr Gln Lys Val Thr Tyr
625 630 635 640
Asp Thr Gln Ala Phe Phe Pro Ile Gly Ser Thr Gly Phe Val Leu Arg
645 650 655
Gly Tyr Gly Lys Leu Gly Tyr Gly Asn Asp Leu Pro Phe Tyr Lys Asn
660 665 670
Phe Tyr Ala Gly Gly Tyr Gly Ser Val Arg Gly Tyr Asp Asn Ser Thr
675 680 685
Leu Gly Pro Lys Tyr Ala Ser Val Asn Leu Gln Glu Glu Lys Lys Asn
690 695 700
Asp Ser Ser Pro Glu Glu Val Gly Gly Asn Ala Leu Val Gln Phe Gly
705 710 715 720
Thr Glu Leu Val Leu Pro Met Pro Phe Lys Gly Asp Trp Thr Arg Gln
725 730 735
Val Arg Pro Val Leu Phe Ala Glu Gly Gly Gln Val Phe Asp Thr Lys
740 745 750
Cys Asp Val Arg Ser Tyr Ser Met Ile Met Asn Gly Gln Gln Ile Ser
755 760 765
Asp Ala Lys Lys Tyr Cys Glu Asp Asn Tyr Gly Phe Asp Leu Gly Asn
770 775 780
Leu Arg Tyr Ser Val Gly Val Gly Val Thr Trp Ile Thr Met Ile Gly
785 790 795 800
Pro Leu Ser Leu Ser Tyr Ala Phe Pro Leu Asn Asp Lys Pro Gly Asp
805 810 815
Glu Thr Lys Glu Ile Gln Phe Glu Ile Gly Arg Thr Phe
820 825
<210> 30
<211> 458
<212> PRT
<213> Acinetobacter baumannii
<400> 30
Met Arg Gly Pro Glu Pro Val Val Lys Thr Asp Ile Pro Gln Ser Tyr
1 5 10 15
Ala Tyr Asn Ser Ala Ser Gly Thr Ser Ile Ala Glu Gln Gly Tyr Lys
20 25 30
Gln Phe Phe Ala Asp Pro Arg Leu Leu Glu Val Ile Asp Leu Ala Leu
35 40 45
Ala Asn Asn Arg Asp Leu Arg Thr Ala Thr Leu Asn Ile Glu Arg Ala
50 55 60
Gln Gln Gln Tyr Gln Ile Thr Gln Asn Asn Gln Leu Pro Thr Ile Gly
65 70 75 80
Ala Ser Gly Ser Ala Ile Arg Gln Val Ser Gln Ser Arg Asp Pro Asn
85 90 95
Asn Pro Tyr Ser Thr Tyr Gln Val Gly Leu Gly Val Thr Ala Tyr Glu
100 105 110
Leu Asp Phe Trp Gly Arg Val Arg Ser Leu Lys Asp Ala Ala Leu Asp
115 120 125
Ser Tyr Leu Ala Thr Gln Ser Ala Arg Asp Ser Thr Gln Ile Ser Leu
130 135 140
Ile Ser Gln Val Ala Gln Ala Trp Leu Asn Tyr Ser Phe Ala Thr Ala
145 150 155 160
Asn Leu Arg Leu Ala Glu Gln Thr Leu Lys Ala Gln Leu Asp Ser Tyr
165 170 175
Asn Leu Asn Lys Lys Arg Phe Asp Val Gly Ile Asp Ser Glu Val Pro
180 185 190
Leu Arg Gln Ala Gln Ile Ser Val Glu Thr Ala Arg Asn Asp Val Ala
195 200 205
Asn Tyr Lys Thr Gln Ile Ala Gln Ala Gln Asn Leu Leu Asn Leu Leu
210 215 220
Val Gly Gln Pro Val Pro Gln Asn Leu Leu Pro Thr Gln Pro Val Lys
225 230 235 240
Arg Ile Ala Gln Gln Asn Val Phe Thr Ala Gly Leu Pro Ser Asp Leu
245 250 255
Leu Asn Asn Arg Pro Asp Val Lys Ala Ala Glu Tyr Asn Leu Ser Ala
260 265 270
Ala Gly Ala Asn Ile Gly Ala Ala Lys Ala Arg Leu Phe Pro Thr Ile
275 280 285
Ser Leu Thr Gly Ser Ala Gly Tyr Ala Ser Thr Asp Leu Ser Asp Leu
290 295 300
Phe Lys Ser Gly Gly Phe Val Trp Ser Val Gly Pro Ser Leu Asp Leu
305 310 315 320
Pro Ile Phe Asp Trp Gly Thr Arg Arg Ala Asn Val Lys Ile Ser Glu
325 330 335
Thr Asp Gln Lys Ile Ala Leu Ser Asp Tyr Glu Lys Ser Val Gln Ser
340 345 350
Ala Phe Arg Glu Val Asn Asp Ala Leu Ala Thr Arg Ala Asn Ile Gly
355 360 365
Glu Arg Leu Thr Ala Gln Gln Arg Leu Val Glu Ala Thr Asn Arg Asn
370 375 380
Tyr Thr Leu Ser Asn Ala Arg Phe Arg Ala Gly Ile Asp Ser Tyr Leu
385 390 395 400
Thr Val Leu Asp Ala Gln Arg Ser Ser Tyr Ala Ala Glu Gln Gly Leu
405 410 415
Leu Leu Leu Gln Gln Ala Asn Leu Asn Asn Gln Ile Glu Leu Tyr Lys
420 425 430
Thr Leu Gly Gly Gly Leu Lys Ala Asn Thr Ser Asp Thr Val Val His
435 440 445
Gln Pro Ser Ser Ala Glu Leu Lys Lys Gln
450 455
<210> 31
<211> 412
<212> PRT
<213> Acinetobacter baumannii
<400> 31
Met Met Ser Gly Ala Asn Ala Ala Thr Ser Asp Lys Glu Glu Ile Arg
1 5 10 15
Lys Leu Arg Gln Glu Val Glu Ala Leu Lys Ala Leu Val Gln Glu Gln
20 25 30
Arg Gln Val Gln Gln Gln Gln Gln Gln Val Gln Gln Gln Gln Gln Val
35 40 45
Gln Leu Ala Glu Val Lys Ala Gln Pro Gln Pro Val Ala Ala Pro Val
50 55 60
Ser Pro Leu Ala Gly Phe Lys Ser Lys Ala Gly Ala Asp Val Asn Leu
65 70 75 80
Tyr Gly Phe Val Arg Gly Asp Ala Asn Tyr Ile Ile Glu Gly Ala Asp
85 90 95
Asn Asp Phe Gly Asp Val Ser Lys Ser Asp Gly Lys Thr His Asp Lys
100 105 110
Leu Arg Ala Thr Ala Lys Thr Thr Arg Leu Gly Leu Asp Phe Asn Thr
115 120 125
Pro Val Gly Asp Asp Lys Val Gly Gly Lys Ile Glu Val Asp Phe Ala
130 135 140
Gly Ser Thr Thr Asp Ser Asn Gly Ser Leu Arg Ile Arg His Ala Tyr
145 150 155 160
Leu Thr Tyr Asn Asn Trp Leu Phe Gly Gln Thr Thr Ser Asn Phe Leu
165 170 175
Ser Asn His Ala Pro Glu Met Ile Asp Phe Ser Thr Asn Ile Gly Gly
180 185 190
Gly Thr Lys Arg Val Pro Gln Val Arg Tyr Asn Tyr Lys Leu Gly Pro
195 200 205
Thr Thr Gln Leu Phe Val Ser Ala Glu Lys Gly Asp Ser Thr Thr Ser
210 215 220
Val Thr Gly Asp Ser Ile Lys Tyr Ser Leu Pro Ala Leu Thr Ala Lys
225 230 235 240
Ile Thr Gln Gly Tyr Ala Glu Gly Arg Gly Ser Ala Ser Ala Arg Val
245 250 255
Leu Val Glu Asn Tyr Lys Ser Gln Leu Ala Asp Asp Asp Lys Thr Gly
260 265 270
Trp Gly Val Ala Val Gly Thr Asp Phe Lys Val Ser Asp Pro Leu Lys
275 280 285
Leu Phe Ala Asp Ala Ser Tyr Val Val Gly Asp Asn Ser Tyr Leu Tyr
290 295 300
Gly Ser Asn Ser Pro Tyr Ala Val Asp Gly Asn Ser Ile Glu Gln Asn
305 310 315 320
Glu Phe Val Ala Val Gln Val Gly Gly Thr Tyr Lys Ile Leu Pro Asn
325 330 335
Leu Arg Ser Thr Leu Ala Tyr Gly Ala Gln Phe Ser Asp Asp Gly Thr
340 345 350
Asp Tyr Ala Arg Leu Asn Ala Ser Ala Asn Glu Lys Val Gln Gln Ala
355 360 365
Trp Ile Asn Phe Ile Tyr Thr Pro Val Lys Pro Ile Asp Leu Gly Val
370 375 380
Glu Tyr Val Asn Gly Lys Arg Asp Thr Phe Asp Gly Lys Ser Tyr Lys
385 390 395 400
Asp Asn Arg Val Gly Leu Met Ala Lys Tyr Ser Phe
405 410
<210> 32
<211> 233
<212> PRT
<213> putative outer membrane protein
<400> 32
Tyr Gln Ala Glu Val Gly Gly Ser Tyr Asn Tyr Leu Asp Pro Asp Asn
1 5 10 15
Gly Ser Ser Val Ser Lys Phe Gly Val Asp Gly Thr Tyr Tyr Phe Asn
20 25 30
Pro Val Gln Thr Arg Asn Ala Pro Leu Ala Glu Ala Ala Phe Leu Asn
35 40 45
Arg Ala Ser Asn Val Asn Ala His Val Asn Tyr Gly Asp Asn Ser Gly
50 55 60
Thr Lys Asp Thr Gln Tyr Gly Val Gly Val Glu Tyr Phe Val Pro Asn
65 70 75 80
Ser Asp Phe Tyr Leu Ser Gly Asp Val Gly Arg Asn Glu Arg Glu Ile
85 90 95
Asp Asn Thr Asn Ile Asp Ser Lys Val Thr Thr Tyr Ala Ala Glu Val
100 105 110
Gly Tyr Leu Pro Ala Pro Gly Leu Leu Leu Ala Leu Gly Val Lys Gly
115 120 125
Tyr Asp Glu Lys Asp Gly Lys Asp Gly Ala Asp Pro Thr Val Arg Ala
130 135 140
Lys Tyr Val Thr Gln Val Gly Gln His Asp Val Asn Leu Glu Ala Tyr
145 150 155 160
Gly Ala Phe Gly Asp Leu Asp Glu Tyr Lys Val Arg Gly Asp Tyr Tyr
165 170 175
Ile Asp Lys Thr Leu Ser Leu Gly Val Asp Tyr Tyr Asn Asn Asp Leu
180 185 190
Thr Asp Lys Asp Glu Phe Gly Ile Asn Ala Lys Lys Phe Leu Asn Gln
195 200 205
Gln Val Ser Val Glu Gly Arg Val Gly Phe Gly Asp Asn Asp Asn Thr
210 215 220
Tyr Gly Val Arg Ala Ala Tyr Arg Phe
225 230
<210> 33
<211> 364
<212> PRT
<213> Acinetobacter baumannii
<400> 33
Met Gly Cys Ser Ser Asn Pro Ser Lys Lys Glu Val Val Asp Thr Gly
1 5 10 15
Pro Gln Ser Ser Glu Gln Ala Tyr Phe Asp Lys Ala Gln Lys Ala Leu
20 25 30
Asp Arg Gly Gln Tyr Leu Asp Ala Thr Lys Ser Leu Glu Ala Ile Asp
35 40 45
Thr Tyr Tyr Pro Thr Gly Gln Tyr Ala Gln Gln Ala Gln Leu Glu Leu
50 55 60
Leu Tyr Ser Lys Phe Lys Gln Lys Asp Tyr Glu Gly Ala Ile Ala Leu
65 70 75 80
Ala Glu Arg Phe Ile Arg Leu Asn Pro Gln His Pro Asn Val Asp Tyr
85 90 95
Ala Tyr Tyr Val Arg Gly Val Ser Asn Met Glu Met Asn Tyr Asp Ser
100 105 110
Leu Leu Arg Tyr Thr Ser Leu Gln Gln Ser His Arg Asp Val Ser Tyr
115 120 125
Leu Lys Val Ala Tyr Gln Asn Phe Val Asp Leu Ile Arg Arg Phe Pro
130 135 140
Ser Ser Gln Tyr Ser Val Asp Ala Ala Gln Arg Met Lys Phe Ile Gly
145 150 155 160
Gln Glu Leu Ala Glu Ser Glu Met Asn Ala Ala Arg Phe Asn Val Lys
165 170 175
Arg Lys Ala Trp Ile Ala Ala Ala Glu Arg Ser Gln Trp Val Ile Glu
180 185 190
His Tyr Pro Gln Thr Pro Gln Val Pro Glu Ala Leu Ala Thr Leu Ala
195 200 205
Tyr Ser Tyr Asp Gln Leu Gly Asp Lys Ala Thr Ser Gln Gln Tyr Ile
210 215 220
Glu Val Leu Lys Leu Asn Tyr Pro Ser Leu Val Asn Lys Asn Gly Thr
225 230 235 240
Val Asn Met Arg Ala Ala Arg Lys Glu Gly Asn Trp Ile Asn Arg Ala
245 250 255
Thr Leu Gly Ile Leu Gly Arg Glu Ser Lys Ser Val Thr Pro Asp Thr
260 265 270
Thr Thr Ser Ser Glu Ala Glu Pro Lys Arg Ser Leu Leu Asn Arg Val
275 280 285
Ser Phe Gly Leu Ile Gly Asn Ser Gly Lys Glu Glu Thr Glu Glu Thr
290 295 300
Thr Asn Thr Pro Val Glu Ala Pro Lys Ser Glu Arg Ser Trp Thr Asn
305 310 315 320
Arg Leu Ser Phe Gly Leu Leu Asp Lys Pro Lys Pro Lys Ala Ala Glu
325 330 335
Gly Ala Thr Ile Ala Pro Ala Thr Ser Ser Ser Glu Ala Pro Ser Ala
340 345 350
Ser Pro Ala Asp Asn Glu Ala Asp Asp Ala Ala Gln
355 360
<210> 34
<211> 356
<212> PRT
<213> Acinetobacter baumannii
<400> 34
Met Lys Leu Ser Arg Ile Ala Leu Ala Thr Met Leu Val Ala Ala Pro
1 5 10 15
Leu Ala Ala Ala Asn Ala Gly Val Thr Val Thr Pro Leu Leu Leu Gly
20 25 30
Tyr Thr Phe Gln Asp Ser Gln His Asn Asn Gly Gly Lys Asp Gly Asn
35 40 45
Leu Thr Asn Gly Pro Glu Leu Gln Asp Asp Leu Phe Val Gly Ala Ala
50 55 60
Leu Gly Ile Glu Leu Thr Pro Trp Leu Gly Phe Glu Ala Glu Tyr Asn
65 70 75 80
Gln Val Lys Gly Asp Val Asp Gly Ala Ser Ala Gly Ala Glu Tyr Lys
85 90 95
Gln Lys Gln Ile Asn Gly Asn Phe Tyr Val Thr Ser Asp Leu Ile Thr
100 105 110
Lys Asn Tyr Asp Ser Lys Ile Lys Pro Tyr Val Leu Leu Gly Ala Gly
115 120 125
His Tyr Lys Tyr Asp Phe Asp Gly Val Asn Arg Gly Thr Arg Gly Thr
130 135 140
Ser Glu Glu Gly Thr Leu Gly Asn Ala Gly Val Gly Ala Phe Trp Arg
145 150 155 160
Leu Asn Asp Ala Leu Ser Leu Arg Thr Glu Ala Arg Ala Thr Tyr Asn
165 170 175
Ala Asp Glu Glu Phe Trp Asn Tyr Thr Ala Leu Ala Gly Leu Asn Val
180 185 190
Val Leu Gly Gly His Leu Lys Pro Ala Ala Pro Val Val Glu Val Ala
195 200 205
Pro Val Glu Pro Thr Pro Val Ala Pro Gln Pro Gln Glu Leu Thr Glu
210 215 220
Asp Leu Asn Met Glu Leu Arg Val Phe Phe Asp Thr Asn Lys Ser Asn
225 230 235 240
Ile Lys Asp Gln Tyr Lys Pro Glu Ile Ala Lys Val Ala Glu Lys Leu
245 250 255
Ser Glu Tyr Pro Asn Ala Thr Ala Arg Ile Glu Gly His Thr Asp Asn
260 265 270
Thr Gly Pro Arg Lys Leu Asn Glu Arg Leu Ser Leu Ala Arg Ala Asn
275 280 285
Ser Val Lys Ser Ala Leu Val Asn Glu Tyr Asn Val Asp Ala Ser Arg
290 295 300
Leu Ser Thr Gln Gly Phe Ala Trp Asp Gln Pro Ile Ala Asp Asn Lys
305 310 315 320
Thr Lys Glu Gly Arg Ala Met Asn Arg Arg Val Phe Ala Thr Ile Thr
325 330 335
Gly Ser Arg Thr Val Val Val Gln Pro Gly Gln Glu Ala Ala Ala Pro
340 345 350
Ala Ala Ala Gln
355
<210> 35
<211> 581
<212> PRT
<213> Acinetobacter baumannii
<400> 35
Met Asn Gln Glu Thr Gly Arg Gly Val Thr Arg Gly Thr Lys Leu Tyr
1 5 10 15
Val Lys Asp Val Pro Val Leu Ala Val Pro Tyr Phe Asn Phe Pro Ile
20 25 30
Asp Asp Arg Arg Thr Thr Gly Ile Leu Asn Pro Gln Phe Gly Phe Ser
35 40 45
Asn Asp Gly Gly Ile Glu Leu Ser Val Pro Val Tyr Leu Asn Leu Ala
50 55 60
Pro Asn Tyr Asp Ala Thr Ile Thr Pro Arg Tyr Leu Ala Asp Arg Gly
65 70 75 80
Ala Met Leu Gln Gly Glu Phe Arg Tyr Leu Thr Asp Gly Phe Gly Ala
85 90 95
Gly Gln Ile Trp Gly Gly Ile Leu Pro Ser Asp Lys Glu Tyr Asp Asp
100 105 110
Lys Asp Arg Lys Asp Phe His Phe Leu His Asn Trp Asp Ile Asn Asp
115 120 125
Gln Trp Ser Thr Asn Leu Glu Tyr Asn Tyr Ala Ser Asp Lys Asp Tyr
130 135 140
Phe Ser Asp Leu Asp Ser Ser Pro Ile Ser Lys Thr Asp Leu Asn Leu
145 150 155 160
Arg Arg Ala Trp Glu Leu Asn Tyr Gln His Gly Ile Pro Gly Leu Lys
165 170 175
Ala Gln Leu Lys Val Glu Asp Phe Gln Thr Leu Asp Pro Gln Val Lys
180 185 190
Asp Ala Asp Lys Pro Tyr Ala Arg Leu Pro Gln Phe Leu Leu Asn Tyr
195 200 205
Val Thr Gly Asn Pro Leu Gly Leu Gln Tyr Glu Phe Asn Asn Asp Thr
210 215 220
Ala Tyr Phe Lys Lys Ser Ile Asn Asp Asn Ser Ala Gln Glu Ser Ser
225 230 235 240
Gly Thr Arg Ile Tyr Asn Gln Phe Ala Thr Arg Tyr Asn Tyr Arg Thr
245 250 255
Pro Ala Ala Phe Val Ile Pro Glu Val Ser Val Arg Ser Ile Gln Thr
260 265 270
Phe Tyr Asp Lys Asp Thr Gln Leu Asn Asn Pro Gly Gly Ser Glu Asn
275 280 285
Lys Ser Val Val Val Pro Gln Phe Thr Leu Asp Thr Gly Leu Asn Phe
290 295 300
Glu Arg Glu Gly Lys Tyr Leu Gln Thr Leu Thr Pro Arg Ala Phe Tyr
305 310 315 320
Ala Tyr Ala Pro Tyr Lys Asn Gln Asp Gly Tyr Pro Asn Phe Asp Ser
325 330 335
Thr Thr Ala Ser Ile Ser Tyr Asp Gln Leu Phe Asn Pro Tyr Arg Phe
340 345 350
Tyr Gly His Asp Arg Leu Glu Asp Asn Asn Phe Leu Ser Leu Gly Val
355 360 365
Ser Tyr Ser Leu Phe Asp Thr Val Gly Leu Glu Arg Leu Arg Ala Ser
370 375 380
Val Gly Gln Ser Tyr Tyr Phe Glu Asp Arg Arg Val Thr Leu Lys Gln
385 390 395 400
Gly Gln Asp Glu Phe Asp Thr Glu Arg Lys Thr Gly Pro Val Ile Ser
405 410 415
Leu Ser Ser Gln Leu Asn Gln Asn Phe Thr Ile Ala Ala Asn Ser Ala
420 425 430
Trp Met Ser Asn Gly Asp Asn Ala Gln Arg Asp Phe Gln Val Tyr Tyr
435 440 445
Thr Gly Asp Lys Gly Asn Leu Tyr Asn Leu Gly Tyr Phe Tyr Arg Lys
450 455 460
Asp Ile Pro Gly Arg Gln Asp Thr Tyr Asp Gln Val Val Ala Ser Phe
465 470 475 480
Ile Gln Pro Ile Lys Asp Asn Trp Arg Ile Met Gly His Val Gln Tyr
485 490 495
Asp Met Asp Asn Asp Val Ala Arg Glu Leu Leu Leu Gly Val Asn Tyr
500 505 510
Glu Ser Cys Cys Trp Gly Ile Ser Val Tyr Gly Arg Ser Tyr Tyr Asn
515 520 525
Asp Leu Asp Asp Pro Lys Thr Ser Asp Val Ser Glu Lys Arg Ala Ile
530 535 540
Met Ala Glu Ile Thr Leu Lys Gly Leu Gly Gly Leu Asn Asn Lys Leu
545 550 555 560
Ala Ser Leu Leu Glu Asn Arg Phe Leu Gly Phe Asn Lys Ile Asn Gln
565 570 575
Ser Trp Thr Gln Arg
580
<210> 36
<211> 747
<212> PRT
<213> Acinetobacter baumannii
<400> 36
Met Ser Ser Glu Lys Arg Asp Leu Thr Asn Phe Ser Arg Phe Leu Val
1 5 10 15
Asn Ile Asn Tyr Val Asp Phe Pro Glu Tyr Ala Lys Leu Pro Leu Ile
20 25 30
Gln Asn Phe Arg Asp Phe Lys His Phe Lys Thr Ala Ile Asp Trp Ser
35 40 45
Asn Lys Phe Asn Ile Gln Lys Ser Val Asp Gly Arg Ile Leu Leu Ser
50 55 60
Val Leu Tyr Ala Glu Ala Gln Asp Val Ala Asn Ala Lys Asp Gln Leu
65 70 75 80
Ser Lys Ile Asp Ile Lys Gly Leu Thr Ala Asp Gln Leu Val Arg Val
85 90 95
Ala Tyr Ala Tyr Arg Leu Ile Asn Leu Pro Val Asp Ala Leu Ala Thr
100 105 110
Val Glu His Ala Tyr Gln Gln Gln Pro Lys Ser Leu Ser Val Leu Gln
115 120 125
Glu Tyr Val Tyr Asp Leu Ile Ala Ile Gly Ser Tyr Lys Lys Ala Gln
130 135 140
Gln Leu Leu Gln Ala Ser Glu Lys Thr Glu Gln Thr Val Gln Met Leu
145 150 155 160
Lys Thr Leu Gln Val Ser Glu Phe Ser Gln His Ile Asn Asn Ala Ile
165 170 175
Ala Arg Tyr Lys Tyr Leu Asn Arg Glu Gly Leu Ser Asp Ala Glu Ser
180 185 190
Phe Ala Glu Leu Asp Lys Val Leu Glu Gln Gly Gln Lys Met His Gln
195 200 205
Gln Met Asn Pro Ser Asp Pro Asn Tyr Leu Arg Phe Tyr Tyr Asp Tyr
210 215 220
Leu Tyr Gly Leu Asp Phe Arg Gly Arg Ser Lys Ala Val Ile Glu Ser
225 230 235 240
Phe Thr Gln Leu Asn Ile Pro Leu Glu Lys Leu Pro Ala Tyr Val Arg
245 250 255
His Ala Ile Ala Asp Ser Tyr Leu Ala Glu Gln Lys Pro Lys Gln Ala
260 265 270
Glu Phe Ala Tyr Lys Thr Leu Leu Thr Glu Lys Asn Tyr Pro Asp Met
275 280 285
Thr Val Tyr Thr Gly Leu Tyr Tyr Ser Tyr Ile Glu Gln Glu Lys Tyr
290 295 300
Lys Glu Ala Glu Gln Leu Leu Ala Glu Val Asp Arg Leu Ile Pro Thr
305 310 315 320
Tyr Lys Tyr Ser Gln Ala Lys Gly Val Asp Lys Ile Ser His Pro Asp
325 330 335
Arg Asp Asp Tyr Ile Ala Leu Gln Gly Met His Leu Ala Tyr Ala Asn
340 345 350
His Leu Asp Gln Ala Glu Lys His Phe Gln Lys Lys Val Glu Gln Ala
355 360 365
Pro Ala Asn Glu Ser Leu Ile Asn Asn Leu Ala Arg Val Glu Arg Trp
370 375 380
Arg Glu Lys Pro Leu Glu Ala Lys Lys Thr Ile Ser Arg Leu Asn Gly
385 390 395 400
Ile Asp Pro Ile Ala Lys Asp Thr Arg Ile Asn Glu Met Gln Asn Ala
405 410 415
Gln Ala Leu Gly Asp Ile Pro Thr Trp Arg Lys Thr Thr Gln Asn Leu
420 425 430
Val Gln Tyr Tyr Pro Asp Asp Ser Gly Val Ile Lys Ser Arg Lys Glu
435 440 445
Leu Glu Asp Arg Asn Arg Ala Thr Ile Ser His Ser Thr Thr Trp Gly
450 455 460
Gln Ser Lys Ala Asp Gly Arg Asp Thr Val Ser Gly Gln Asn Gly Leu
465 470 475 480
Lys Asp Arg Glu Met Glu Thr Arg Leu Asn Ser Pro Trp Ile Asn Asp
485 490 495
Asn Tyr Arg Leu Phe Ala Trp His Gln Asp Arg Tyr Gly Glu Tyr Arg
500 505 510
Phe Gly Asp Val His Asp Gln Arg Tyr Gly Val Gly Ala Glu Trp Gln
515 520 525
Ala Asn Arg Lys Ala Leu Ser Ala Ile Val Ser Gln Ser Thr Asp Gly
530 535 540
Gly Gln Ala Gly Val Arg Leu Asp Trp Ser Gln Trp Leu Asn Asp His
545 550 555 560
Trp Gln Tyr Gln Leu Gln Tyr Asn Ser Gln Ala Asp Ile Pro Leu Gln
565 570 575
Ala Leu Asp Ala Gly Glu Asp Gly Gln Ser Tyr Arg Ala Ala Val Thr
580 585 590
Trp Gln Lys Asp Glu Ser Arg Gln Ile Gly Ala Ser Tyr Gly Leu Thr
595 600 605
Asp Ile Ser Asp Gly Asn Lys Gln Gln Glu Phe Ser Thr Phe Trp Arg
610 615 620
Glu Arg Leu Phe Asp Ala Pro His His Ile Thr Tyr Gly Thr Val Arg
625 630 635 640
Gly Phe Tyr Gly Thr Asn Ser Gln Asp Gln Thr Ala Tyr Phe Ser Pro
645 650 655
Ser Ser His Tyr Ser Ala Glu Leu Asn Leu Ser His Asp Trp Val Thr
660 665 670
Trp Arg Glu Tyr Glu Arg Ser Phe Lys Gln His Phe Glu Ala Gly Val
675 680 685
Gly Leu Tyr Lys Gln Ala Asp Tyr Ser Ala Lys Pro Thr Tyr Ser Leu
690 695 700
Gln Tyr Gln His Gln Trp Gln Leu Ser Arg Thr Trp Gln Leu Asn Tyr
705 710 715 720
Gly Ile Gly Trp Gln Tyr His Pro Tyr Asp Gly His Asp Glu Gln His
725 730 735
Thr Tyr Gly Ile Phe Gly Phe Glu Gly Arg Phe
740 745
<210> 37
<211> 381
<212> PRT
<213> Acinetobacter baumannii
<400> 37
Met Leu Gly Asp Trp Asn Gly Gln Arg Thr Ala Leu Gln Ala Gln Gly
1 5 10 15
Tyr Asp Phe Ser Phe Gly Tyr Thr Gly Glu Tyr Ala Gly Ile Leu Asp
20 25 30
Ser Lys Gln Thr Ser Thr His Gly Ser Ala Tyr Thr Gly Gln Leu Ala
35 40 45
Leu Gly Ser His Leu Asp Leu Gly Lys Ile Leu Gly Trp Gln Asp Thr
50 55 60
Glu Ala Gln Ile Thr Leu Thr Tyr Arg Asp Gly Gln Ser Leu Ser Glu
65 70 75 80
His Ser Pro Ala Leu Ala Gly His Gln Ser Ser Val Gln Glu Val Trp
85 90 95
Gly Arg Glu Gln Thr Trp Arg Leu Thr Asp Leu Trp Ile Lys Lys Lys
100 105 110
Phe Leu Asp Gln Lys Leu Asp Val Lys Val Gly Arg Phe Gly Glu Gly
115 120 125
Glu Asp Phe Asn Ser Phe Asp Cys Asp Phe Gln Asn Leu Ala Leu Cys
130 135 140
Gly Ser Gln Val Gly Asn Trp Val Gly Asp Gln Trp Tyr Asn Trp Pro
145 150 155 160
Val Ser Gln Trp Ala Met Arg Val Lys Tyr Asn Leu Gln Pro Asp Leu
165 170 175
Tyr Thr Gln Val Gly Val Tyr Glu Tyr Asn Pro Glu Asn Leu Glu Arg
180 185 190
Gly Lys Gly Phe Asn Leu Ser Thr Asp Gly Ser His Gly Ala Ile Ile
195 200 205
Pro Ala Glu Val Val Trp Ser Pro Lys Leu Gly Val Gln Ser Met Pro
210 215 220
Gly Glu Tyr Arg Leu Gly Tyr Tyr Tyr Ser Thr Ala Asp Ala Lys Glu
225 230 235 240
Ile Ala Asp Ser Thr Lys Thr Ser His Lys Gln Gly Val Trp Val Thr
245 250 255
Ala Lys Gln Lys Leu Phe Gln Pro Ala Asp Gln Thr Asp Arg Gly Leu
260 265 270
Thr Gly Phe Val Asn Leu Thr Phe His Asp Ser Asp Thr Asn Lys Val
275 280 285
Asp Asn Met Gln Asn Ile Gly Leu Val Tyr Lys Gly Leu Leu Asn Gln
290 295 300
Arg Pro Gln Asp Glu Leu Ala Leu Gly Val Ala Arg Ile His Ile Asn
305 310 315 320
Asp Asp Trp Ser Asp Val Gln Ala Lys Glu Tyr Asp Thr Glu Tyr Asn
325 330 335
Thr Glu Leu Tyr Tyr Gly Ile His Ala Thr Asn Trp Leu Thr Ile Arg
340 345 350
Pro Asn Val Gln Tyr Val Arg His Val Gly Ala Leu Lys Asn Gly Asp
355 360 365
Asn Thr Trp Val Gly Gly Ile Lys Phe Ser Thr Ala Phe
370 375 380
<210> 38
<211> 183
<212> PRT
<213> Acinetobacter baumannii
<400> 38
Met Leu Phe Arg Thr Gly Leu Ala Asp Gly Leu Glu Leu Gln Leu Gly
1 5 10 15
Trp Gln Gly Pro Ala Trp Thr Gln Thr Lys Arg Ala Gly Lys Lys Thr
20 25 30
Asp Asn Ser Gly Phe Gly Asp Val Ser Ile Gly Leu Lys Lys Ala Ile
35 40 45
Asp Leu Asn Asp Glu Asn Leu Thr Met Ala Val Leu Ala Glu Ala Val
50 55 60
Ile Ala Thr Gly Asn Asp Glu Phe Thr Ala His Asp Asp Ile Tyr Ser
65 70 75 80
Leu Ser Ser Ala Val Ala Tyr Lys Tyr Asn Asp Leu Leu Asp Thr Ser
85 90 95
Ile Thr Met Arg Tyr Glu Val Gln Asn Ser Asn Trp Ala Val Thr Ala
100 105 110
Ile Pro Thr Ile Asn Tyr Lys Ile Ala Gly Lys Leu Ser Gly Tyr Ser
115 120 125
Glu Phe Val Tyr Arg Lys Ala Glu Ser Gln Asp Tyr Gln Tyr Gly Leu
130 135 140
Gly Thr Gly Leu Val Tyr Ala Val Asn Asn Arg Thr Gln Leu Asp Ala
145 150 155 160
Asn Ile Gly Val Asp Leu Glu Gly Gln Asp Lys Ser Tyr Lys Gly Gly
165 170 175
Leu Gly Met Ala Phe Leu Phe
180
<210> 39
<211> 217
<212> PRT
<213> Acinetobacter baumannii
<400> 39
Met Arg Ala Leu Val Ile Ser Thr Val Val Gly Ala Ala Val Val Leu
1 5 10 15
Ser Gly Cys Gln Thr Thr Gly Asn Asn Leu Gly Gly Val Glu Tyr Asp
20 25 30
Lys Ala Ala Leu Gly Thr Leu Ile Gly Ala Ala Ala Gly Tyr Gly Ile
35 40 45
Ser Lys Ser Asn Ala Asn Ser Ser Arg Gln Asn Asn Arg Ala Ala Ala
50 55 60
Ile Gly Ala Val Leu Gly Ala Ala Gly Gly Leu Tyr Leu Asp Gln Lys
65 70 75 80
Glu Lys Lys Leu Arg Glu Gln Met Ala Gly Thr Gly Val Glu Val Gly
85 90 95
Arg Asn Pro Asp Gly Ser Val Gln Leu Ile Met Pro Gly Ser Ile Thr
100 105 110
Phe Asp Thr Asn Lys Ser Asn Ile Lys Pro Asn Phe Tyr Ala Thr Leu
115 120 125
Asp Lys Val Ala Gln Thr Leu Ala Glu Asp Asn Lys Ser Ala Ile Leu
130 135 140
Val Thr Gly Tyr Thr Asp Asn Thr Gly Asn Asp Ser Ile Asn Ile Pro
145 150 155 160
Leu Ser Gln Ala Arg Ala Gln Ser Val Lys Asn Tyr Leu Ala Gly Lys
165 170 175
Gly Val Pro Ser Ser Arg Ile Asp Ala Gln Gly Tyr Gly Ser Ser Asn
180 185 190
Pro Ile Ala Asp Asn Ser Thr Ala Ser Gly Arg Glu Gln Asn Arg Arg
195 200 205
Val Glu Ile Ser Ile Tyr Ala Lys Gln
210 215
<210> 40
<211> 299
<212> PRT
<213> Acinetobacter baumannii
<400> 40
Met Lys Lys Leu Gly Leu Ala Thr Ala Val Leu Leu Ala Met Thr Gly
1 5 10 15
Ala His Ala Tyr Gln Phe Glu Val Gln Gly Gln Ser Glu Tyr Val Asp
20 25 30
Thr Thr Ala Asn Asp Lys Asn Phe Thr Gly Asp Val Ala Gly Thr Phe
35 40 45
Tyr Leu Lys Asn Val Asp Thr Ala Lys Gly Pro Leu Ala Glu Ala Ala
50 55 60
Phe Leu Asn Gln Ala Ser Ser Val Ser Leu Gly Tyr Ser Tyr Gln Gln
65 70 75 80
Tyr Asp Gln Asn Asn Val Asn Tyr His Ile Gly Thr Tyr Gly Val Lys
85 90 95
Gly Glu Ala Tyr Val Pro Thr Pro Tyr Leu Pro Val Tyr Ala Ser Ala
100 105 110
Thr Tyr Asn His Thr Asp Val Asp Gly Lys Asn Asn Phe Ser Lys Asp
115 120 125
Asp Asn Gly Asp Arg Tyr Ala Leu Glu Val Gly Ala Met Leu Leu Pro
130 135 140
Asn Phe Leu Met Thr Val Gly Tyr Thr Ser Val Ala Asn Gln Phe Ala
145 150 155 160
Leu Asp Asn Phe Gly Ile Ile Gly Asn Gly Ile Tyr Ser Ala Val Asn
165 170 175
Gln Thr Ala Ala Ile Gln Asn Asp Gln Asp Ala Val Thr Ala Arg Ala
180 185 190
Lys Tyr Val Gly Pro Ile Asp Gly Thr Asn Met Ala Ile Gly Phe Glu
195 200 205
Ala Ala Gly Ala Phe Gly Gln Glu Asn Gln Tyr Gly Leu Lys Thr Asp
210 215 220
Leu Tyr Leu Thr Pro Lys Leu Ser Val Gly Ala Thr Phe Val Gly Asn
225 230 235 240
Asp Gly Glu Ala Asp Ile Lys Gly Asn Asp Leu Gly Glu Phe Arg Gln
245 250 255
Ala Trp Gly Gly Asn Val Asn Tyr Phe Ile Thr Pro Ala Leu Ala Val
260 265 270
Gly Ala Ser Tyr Met Lys Ala Asp Val Lys Lys Ser Ser Tyr Asp Thr
275 280 285
Gln Thr Ile Gly Leu Asn Ala Lys Phe Arg Phe
290 295
<210> 41
<211> 228
<212> PRT
<213> Acinetobacter baumannii
<400> 41
Asp Glu Ala Val Val His Asp Ser Tyr Ala Phe Asp Lys Asn Gln Leu
1 5 10 15
Ile Pro Val Gly Ala Arg Ala Glu Val Gly Thr Thr Gly Tyr Gly Gly
20 25 30
Ala Leu Leu Trp Gln Ala Asn Pro Tyr Val Gly Leu Ala Leu Gly Tyr
35 40 45
Asn Gly Gly Asp Ile Ser Trp Thr Asp Asp Val Ser Val Asn Gly Thr
50 55 60
Lys Tyr Asp Leu Asp Met Asp Asn Asn Asn Val Tyr Leu Asn Ala Glu
65 70 75 80
Ile Arg Pro Trp Gly Ala Ser Thr Asn Pro Trp Ala Gln Gly Leu Tyr
85 90 95
Ile Ala Ala Gly Ala Ala Tyr Leu Asp Asn Asp Tyr Asp Leu Ala Lys
100 105 110
Arg Ile Gly Asn Gly Asp Thr Leu Ser Ile Asp Gly Lys Asn Tyr Gln
115 120 125
Gln Ala Val Pro Gly Gln Glu Gly Gly Val Arg Gly Lys Met Ser Tyr
130 135 140
Lys Asn Asp Ile Ala Pro Tyr Leu Gly Phe Gly Phe Ala Pro Lys Ile
145 150 155 160
Ser Lys Asn Trp Gly Val Phe Gly Glu Val Gly Ala Tyr Tyr Thr Gly
165 170 175
Asn Pro Lys Val Glu Leu Thr Gln Tyr Asn Leu Ala Pro Val Thr Gly
180 185 190
Asn Pro Thr Ser Ala Gln Asp Ala Val Asp Lys Glu Ala Asn Glu Ile
195 200 205
Arg Asn Asp Asn Lys Tyr Glu Trp Met Pro Val Gly Lys Val Gly Val
210 215 220
Asn Phe Phe Trp
225
<210> 42
<211> 609
<212> PRT
<213> Acinetobacter baumannii
<400> 42
Met Gly Phe Asn Ser Ile Gln Ser Gly Gly Thr Asn Gly Asp Val Thr
1 5 10 15
Phe Arg Gly Met Phe Gly Ser Arg Ile Lys Ile Leu Thr Asp Gly Thr
20 25 30
Glu Asn Leu Gly Ala Cys Pro Asn Arg Met Asp Ala Pro Thr Ser Tyr
35 40 45
Ile Ser Pro Glu Ser Tyr Asp Arg Ile Ser Val Ile Lys Gly Pro Gln
50 55 60
Thr Val Gln Tyr Ala Asn Thr Gly Ser Ala Ala Thr Val Leu Phe Glu
65 70 75 80
Arg Gln Pro Glu Lys Leu Thr Ser Glu Lys Pro Tyr Arg Gly Gln Ala
85 90 95
Ser Val Leu Leu Gly Ser Tyr Gly Arg Ile Asp His Asn Ile Glu Ala
100 105 110
Ala Val Gly Asp Glu Lys Lys Tyr Ile Arg Leu Asn Ala Asn Arg Ser
115 120 125
Glu Ser Asn Ser Tyr Gln Asp Gly Asp Gly Asn Thr Val Pro Ser Ala
130 135 140
Trp Lys Lys Trp Asn Ala Asp Val Ala Leu Gly Phe Thr Pro Asp Glu
145 150 155 160
Asn Thr Trp Val Glu Ile Thr Gly Gly Lys Ser Asp Gly Glu Ser Leu
165 170 175
Tyr Ala Gly Arg Ser Met Asp Gly Ser Gln Phe Ala Arg Glu Ser Leu
180 185 190
Gly Leu Arg Phe Glu Lys Lys Asn Ile Thr Asp Val Ile Lys Lys Ile
195 200 205
Glu Gly Gln Val Asn Tyr Ser Tyr Asn Asp His Val Met Asp Asn Phe
210 215 220
Arg Leu Arg Ile Pro Pro Met Thr His Asp Met Met Thr His Gln Met
225 230 235 240
Val Val Asn Pro Ser Glu Met Gln Val Thr Arg Arg Thr Leu Asn Thr
245 250 255
Arg Phe Ala Met Thr Ser Glu Trp Gly Lys Leu Asn Val Ile Thr Gly
260 265 270
Ile Asp Ser Gln Gln Asn His His Ala Glu Ser Met Lys Ser Leu Met
275 280 285
Met Asp Met Pro Leu Thr Thr Asn Met Lys Phe Gln Ser Tyr Gly Ala
290 295 300
Phe Gly Glu Leu Gly Tyr Gln Leu Ser Glu Asn Ser Lys Leu Val Thr
305 310 315 320
Gly Ala Arg Leu Asp Gln Val Lys Ile Asp Ala Leu Lys Leu Asn Asp
325 330 335
Asp Arg Ser Glu Thr Leu Pro Ser Gly Phe Ile Arg Leu Glu Thr Gln
340 345 350
Leu Pro Glu His Asn Ala Lys Ser Tyr Ile Gly Leu Gly Tyr Val Glu
355 360 365
Arg Val Pro Asp Tyr Trp Glu Leu Phe Ser Thr Ala His Gly Asn Ser
370 375 380
Gly Met Pro Lys Pro Thr Phe Asn Asp Leu Asp Thr Glu Lys Thr Leu
385 390 395 400
Gln Leu Asp Met Gly Tyr Gln His Gln His Gly Ala Phe Asn Ser Trp
405 410 415
Ala Ser Ala Tyr Val Gly Leu Ile Asn Asp Tyr Ile Leu Met Ser Tyr
420 425 430
His Asn His Pro Thr Ser Gly Gly His Gly His Gly Ser Ser Phe Ser
435 440 445
Ala Gly Ala Lys Asn Val Asp Ala Thr Ile Ala Gly Ala Glu Ala Gly
450 455 460
Ile Gly Tyr Gln Phe Thr Asp Arg Ile Gln Ala Asp Leu Ser Ala Met
465 470 475 480
Tyr Ala Trp Gly Lys Asn Thr Thr Asp Asp Lys Pro Leu Pro Gln Ile
485 490 495
Ser Pro Leu Glu Gly Arg Leu Asn Ile Arg Tyr Val Ala Asp Lys Tyr
500 505 510
Asn Leu Gly Leu Leu Trp Arg Ala Val Ala Glu Gln Asn Arg Val Ser
515 520 525
Leu His Gln Gly Asn Ile Val Gly Tyr Asp Leu Lys Pro Ser Lys Gly
530 535 540
Phe Ser Thr Leu Ser Leu Asn Gly Ser Tyr Asn Leu Arg Lys Asp Ile
545 550 555 560
Asp Val Ser Val Gly Ile Asp Asn Val Leu Asp Lys Thr Tyr Thr Glu
565 570 575
His Leu Asn Lys Ala Gly Ser Ala Gly Phe Gly Phe Ala Ser Glu Glu
580 585 590
Gln Phe Asn Asn Ile Gly Arg Asn Tyr Trp Val Arg Met Ser Met Lys
595 600 605
Phe
<210> 43
<211> 170
<212> PRT
<213> Acinetobacter baumannii
<400> 43
Met Thr Gly Cys Ala Ser Arg Lys Pro Ala Thr Thr Ala Thr Thr Gly
1 5 10 15
Thr Thr Asn Pro Ser Thr Val Asn Thr Thr Gly Leu Ser Glu Asp Ala
20 25 30
Ala Leu Asn Ala Gln Asn Leu Ala Gly Ala Ser Ser Lys Gly Val Thr
35 40 45
Glu Ala Asn Lys Ala Ala Leu Ala Lys Arg Val Val His Phe Asp Tyr
50 55 60
Asp Ser Ser Asp Leu Ser Thr Glu Asp Tyr Gln Thr Leu Gln Ala His
65 70 75 80
Ala Gln Phe Leu Met Ala Asn Ala Asn Ser Lys Val Ala Leu Thr Gly
85 90 95
His Thr Asp Glu Arg Gly Thr Arg Glu Tyr Asn Met Ala Leu Gly Glu
100 105 110
Arg Arg Ala Lys Ala Val Gln Asn Tyr Leu Ile Thr Ser Gly Val Asn
115 120 125
Pro Gln Gln Leu Glu Ala Val Ser Tyr Gly Lys Glu Ala Pro Val Asn
130 135 140
Pro Gly His Asp Glu Ser Ala Trp Lys Glu Asn Arg Arg Val Glu Ile
145 150 155 160
Asn Tyr Glu Ala Val Pro Pro Leu Leu Lys
165 170
<210> 44
<211> 480
<212> PRT
<213> Acinetobacter baumannii
<400> 44
Met Phe Leu Arg Lys Thr Leu Ser Ile Ala Leu Leu Ala Thr Ala Ser
1 5 10 15
Ser Ala Val Phe Ala Gln Gly Leu Val Leu Asn Asn Asp Asp Leu Arg
20 25 30
Thr Asp Leu Asn Trp Leu Asn Gln Gln Gly Val Ile Asn Ile Ser Thr
35 40 45
Ser Thr Trp Pro Leu Ser Gly Asp Glu Ile Gln Arg Ala Leu Ser Gln
50 55 60
Ala Lys Val Thr His Pro Ala Gln Gln Lys Val Ile Asn Ser Val Leu
65 70 75 80
Asn Ala Leu Lys Ala Asp Asn Asn Thr Val Lys Val Gly Ala Phe Ala
85 90 95
Glu Ser Asp Ile Lys Asn Ile Pro Gln Ala Phe Gly Asp Asn Gln Lys
100 105 110
Ser Gln Tyr Gln Gly Ser Leu Glu Phe Asn Ala Gly Gly Glu Asn Trp
115 120 125
Asp Ala Lys Ile Arg Val Asn Ala Glu Lys Asp Pro Gln Ile Asp Ser
130 135 140
Gly His Asp Val Asn Val Glu Gly Ser Tyr Val Ala Gly Lys Leu Trp
145 150 155 160
Asn Gln Trp Ile Val Ala Gly Gln Ile Pro Thr Trp Trp Gly Pro Gly
165 170 175
His Asp Gly Ser Leu Ile Arg Gly Asp Ala Ser Arg Pro Val Tyr Gly
180 185 190
Val Thr Ala Gln Arg Ala Val Gln Asn Ala Phe Glu Thr Lys Trp Leu
195 200 205
Ser Trp Ile Gly Pro Trp Gln Tyr Gln Ala Phe Ala Gly Gln Leu Asp
210 215 220
Asp Tyr Lys Ala Val Pro Asp Ala Lys Leu Ile Gly Leu Arg Leu Thr
225 230 235 240
Ala Gln Pro Leu Pro Tyr Leu Glu Leu Gly Ala Ser Arg Thr Ile Gln
245 250 255
Trp Gly Gly Asp Gly Arg Ser Glu Ser Phe Ser Ser Leu Trp Asp Ala
260 265 270
Ile Lys Gly Asn Asp Asn Val Tyr Gly Asp Thr Glu Asn Pro Ser Asn
275 280 285
Gln Leu Ala Gly Phe Asp Gly Arg Leu Leu Leu Gln Pro Leu Leu Asn
290 295 300
Ile Pro Val Ser Leu Tyr Gly Gln Tyr Val Gly Glu Asp Glu Ala Gly
305 310 315 320
Tyr Leu Pro Ser Lys Lys Met Tyr Leu Ala Gly Val Asp Tyr Ser Ser
325 330 335
Ser Tyr Asn Asp Met Pro Tyr Gln Leu Tyr Ala Glu Trp Ala Asp Thr
340 345 350
Arg Thr Asn Gly Asp Val Lys Ser Ile Ser Tyr Thr His Ser Val Tyr
355 360 365
Lys Asp Gly Tyr Tyr Gln His Gly Phe Pro Leu Gly His Ala Met Gly
370 375 380
Gly Asp Gly Gln Met Tyr Ser Val Gly Gly Asp Ile Arg Phe Asp Val
385 390 395 400
Met Asn Arg Leu Ser Gly Arg Ala Met Val Val Lys Val Asn Gln Ser
405 410 415
Asn Leu Ala Ile Asn Lys Ala Phe Pro Lys Asp Asp Glu Ile Lys Ala
420 425 430
Leu Asp Leu Thr Trp Thr His Tyr Ile Lys Pro Asp Leu Pro Leu Lys
435 440 445
Ile Asn Gly Trp Val Ser Asp Ser Asp Leu Glu Gly Asn Asp Ala Gly
450 455 460
Ala Ser Ile Gly Val Glu Ile Pro Leu Glu Arg Lys Met Phe Gly Phe
465 470 475 480
<210> 45
<211> 114
<212> PRT
<213> Acinetobacter baumannii
<400> 45
Met Asn Lys Leu Leu Val Ala Leu Gly Leu Ala Ala Thr Val Ala Leu
1 5 10 15
Val Gly Cys Asn Lys Asp Lys Ala Pro Glu Thr Gly Ala Thr Thr Gly
20 25 30
Glu His Leu Glu Asn Ala Ala Gln Gln Ala Thr Ala Asp Ile Lys Ser
35 40 45
Ala Gly Asp Gln Ala Ala Ser Asp Ile Ala Thr Ala Thr Asp Asn Ala
50 55 60
Ser Ala Lys Ile Asp Ala Ala Ala Asp His Ala Ala Asp Ala Thr Ala
65 70 75 80
Lys Ala Ala Ala Glu Thr Glu Ala Thr Ala Arg Lys Ala Thr Ala Asp
85 90 95
Thr Ala Gln Ala Val Glu Asn Ala Ala Ala Asp Val Lys Lys Asp Ala
100 105 110
Gln His
<210> 46
<211> 725
<212> PRT
<213> Acinetobacter baumannii
<400> 46
Met Tyr Glu Tyr Pro Ser Tyr Asp Tyr Arg Gly Asn Phe Lys Ile Thr
1 5 10 15
Val Asp Pro Ser Gln Ile Lys Gln Asn Val Lys Ala Glu Asn Thr Ala
20 25 30
Lys Leu Asp Ala Glu Leu Gln Lys Lys Val Asp Gln Tyr Leu Arg Glu
35 40 45
Gln Lys Val Ala Leu Ser Lys Ala Gln Lys Gln Thr Leu Tyr Ala Ala
50 55 60
Ile Ala Asn Glu Gln Gly Asp Trp Gly Leu Thr Ser Ser Ala Arg Ser
65 70 75 80
Glu Lys Ile Asn Asn Ile Leu Ile Asn Leu Leu Asn Asp Leu Gln Phe
85 90 95
Ser Tyr Asp Gly Ser Ile His Tyr Arg Gln Lys Met Gly Ser Phe Asn
100 105 110
Leu Thr Ala Arg Tyr Glu Lys Pro Thr Leu Leu Val Gln Ala Lys Leu
115 120 125
Pro Met Val Leu Asp Leu Glu Asn Tyr Lys Phe Tyr Ile Asn Tyr Phe
130 135 140
Gly Leu Met Pro Tyr Leu Val Asn Lys Asp Asn Gln Asn Asn Leu Ala
145 150 155 160
Tyr Val Asp Phe Ser Lys Tyr Lys Ala Phe Phe Lys Asn Val Asp Lys
165 170 175
Lys Lys Phe Ile Glu Tyr Leu Lys Ala Ser Ser Ala Val Ser Tyr Arg
180 185 190
Leu Ala Glu Pro Gln Asn Leu Gln Arg Val Ser Leu Thr Glu Ala Asp
195 200 205
Arg Lys Ala Gly Ala Val Glu Arg Ile Arg Leu Lys Thr Thr Val Glu
210 215 220
Gln Leu Leu Leu Glu Val Asp Leu Phe Gly Gln Val Asn Glu Lys Tyr
225 230 235 240
Leu Gln Lys Ser Val Leu Gly Leu Asp Glu Glu Lys Leu Ala Glu Thr
245 250 255
Leu Ala Ala Glu Ile Ala Ala Ser Asp Ala Lys Lys Gly Thr Ala Gly
260 265 270
Lys Glu Glu Gln Lys Val Ser Ser Asp Asp Ala Ala Ala Val Ser Gln
275 280 285
Gln Leu Tyr Ser Leu Val Asn Ala His Leu Gly Asn Thr Ser Thr Ser
290 295 300
Glu Asp Glu Glu Val Glu Ser Ala Ser Ser Glu Glu Ala Ser Asp Val
305 310 315 320
Ala Val Ala Glu Ala Glu Gln Thr Ser Glu Asn Glu Glu Val Val Val
325 330 335
Leu Thr Glu Asp Gln Cys Ile Glu Leu Lys Ser Leu Lys Asn Pro Val
340 345 350
Ala Leu Gly Asp Ile Asn Tyr Cys Gln Ile Tyr Gly Ile Asp Val Leu
355 360 365
Asp Gln Ser Asp Thr Ser Ile Gln Lys Ala Gln Ile Lys Ser Arg Gln
370 375 380
Asp Ala Leu Lys Gln Thr Phe Glu Val Tyr Asn Gln Asn Gln Phe Ile
385 390 395 400
Asn Asp Glu Ala Phe Lys Val Leu Trp Leu Lys His Lys Asp Glu Ile
405 410 415
Glu Gln Ala Leu Pro Lys Gln Arg Asn Pro Ile Thr Ile Asp Val Ala
420 425 430
Leu Asp Asp Lys Gly Arg Ala Val Asn Met Asp Tyr Asp Val Asp Tyr
435 440 445
Thr Pro Ala Glu Phe Lys His Arg Phe Asn Ile Lys Ala Asp Met Gln
450 455 460
Ile Leu Asn Tyr Gly Lys Ala Thr Ser Ile Asp Gln Gln Gln Leu Lys
465 470 475 480
Gln Ala Lys Ser Val Ala Glu Ala Ser Lys Gly Ser Met Leu Glu Asn
485 490 495
Ile Ile Lys Gly Phe Ser Glu Lys Leu Gly Gln Ser Asp Val Ser Glu
500 505 510
His Pro Val Gly Thr His Ser Asp Val Gln Asp Leu Asp Ala Asn Leu
515 520 525
Ala Ile Leu Ala Asp Lys Thr Tyr Asp Ala Thr His Ala Tyr Asp Lys
530 535 540
Thr Tyr Lys Ala Val Phe Ile Ala Lys Leu Thr Ala Glu Lys Pro Ser
545 550 555 560
Tyr Ile Lys Tyr Tyr Ser Val Gln Gln Leu Gln Glu Ile Ala Glu Val
565 570 575
Tyr Ala Tyr Trp Phe Ser Asp Glu Asp Thr Tyr Asn Pro Gln Gly Lys
580 585 590
Ala Leu Glu Arg Ile Thr Ala Leu Gln Lys Lys His His Leu Glu Gln
595 600 605
Asp Asp Gln Phe Asp His Glu Leu Gly Arg Ala Val Asp His Ile Val
610 615 620
Leu Thr Thr Ile Gln Gly Lys Thr Gly Arg Glu Ala Trp Gln Arg Leu
625 630 635 640
Gln Lys Gln Tyr Lys Gln Pro Ala Gln Leu Phe Ser Lys Gln Tyr Gln
645 650 655
Leu Glu Phe Glu Lys Gln Asn Gly Val Ser Ala Glu Glu Lys His Leu
660 665 670
Leu Ser Glu Thr Ala Asp Ile Leu Gly Asn Val Tyr Val Ala Ala His
675 680 685
Lys Lys Gln Leu Ser Glu Lys Thr Ile Gln Asn Leu Lys Pro Glu His
690 695 700
Asn Glu Phe Ile Asp Tyr Glu Ile Phe Arg Glu Val Tyr Lys Gln Met
705 710 715 720
Val Ala Ala Arg Lys
725
<210> 47
<211> 746
<212> PRT
<213> Acinetobacter baumannii
<400> 47
Met Thr Pro Cys Cys Leu Ala Ile Ser Ala Ile Phe Ala Gln Gln Ala
1 5 10 15
Tyr Ala Glu Thr Val Thr Gln Thr Ala Glu Val Ser Glu Asn Ala Thr
20 25 30
Gln Lys Pro Val Ala Gln Leu Gln Lys Ile Val Val Thr Ala Thr Arg
35 40 45
Thr Pro Lys Asn Ile Ala Glu Ile Ala Gly Thr Val Gln Ser Ile Asp
50 55 60
Gln Lys Gln Ile Ile Gln Gln Ala Thr Ala Gly Arg Lys Val Ala Asp
65 70 75 80
Ile Leu Ala Gln Leu Val Pro Ser Leu Ala Ser Ser Ser Gly Thr Thr
85 90 95
Ser Asn Tyr Gly Gln Thr Met Arg Gly Arg Asn Val Leu Val Met Ile
100 105 110
Asp Gly Val Ser Gln Thr Gly Ser Arg Asp Val Ser Arg Gln Leu Asn
115 120 125
Ser Ile Ser Pro Gly Met Ile Glu Arg Ile Glu Val Ile Ser Gly Ala
130 135 140
Thr Ser Ile Tyr Gly Ser Gly Ala Thr Gly Gly Ile Ile Asn Ile Ile
145 150 155 160
Thr Lys Arg Ala Asp Thr Ser Lys Pro Leu Ser Phe Glu Thr Lys Val
165 170 175
Gly Ile Thr Ser Ser Asp Thr Phe Arg Ser Asp Gly Leu Ala Tyr Glu
180 185 190
Val Gly Gln Ser Val Ser Phe Asn Lys Gly Asn Ile Asp Gly Phe Leu
195 200 205
Gly Ala Asn Phe Thr Ser Arg Gly Ser Gln Phe Asp Gly Asn Gly Asp
210 215 220
Arg Ile Ser Leu Ser Pro Trp Gln Gly Ser Thr Met Asp Thr Asp Thr
225 230 235 240
Ile Asp Val Asn Gly Arg Leu Asn Phe Asn Leu Asn Asp Thr Gln Thr
245 250 255
Leu Ser Phe Gly Ala Gln Tyr Tyr Lys Asp Lys Gln Asp Thr Asp Tyr
260 265 270
Gly Pro Asp Tyr Ser Tyr Leu Pro Thr Thr Ser Lys Ser Asn Asp Ala
275 280 285
Thr Thr Pro Thr Tyr Lys Ala Ile Lys Gly Leu Lys Leu Ser Asn Pro
290 295 300
Leu Phe Thr Glu Arg Tyr Ala Val Asn Ser Gln Tyr Gln Asn Gln Asp
305 310 315 320
Phe Leu Gly Gln Ile Leu Asn Val Glu Ala Tyr Tyr Arg Asn Glu Lys
325 330 335
Ser Arg Phe Phe Pro Tyr Gly Leu Ser Asn Lys Ser Val Thr Ser Val
340 345 350
Asn Gln Ser Gln Ser Glu Ile Glu Val Ala Gly Leu Arg Ser Thr Met
355 360 365
Gln Thr Asp Leu Asn Ile Ala Asn Arg Asp Met Lys Ile Thr Tyr Gly
370 375 380
Leu Asp Tyr Asp Trp Glu Lys Asp Lys Gln Phe Val Asp Ile Leu Ala
385 390 395 400
Thr Gln Tyr Pro Tyr Leu Val Tyr Thr Pro Thr Gly Gln Arg Lys Gly
405 410 415
Tyr Gly Pro Asn Thr Glu Ile Gln Asn Ile Gly Ala Phe Val Gln Ser
420 425 430
Asp Tyr Ala Val Thr Asp Lys Leu Asn Leu Gln Ala Gly Ile Arg Tyr
435 440 445
Gln Tyr Ile Gln Ala Asp Thr Asp Ala Tyr Ile Pro Ser Arg Glu Thr
450 455 460
Thr Met Val Pro Ala Gly Ser Thr His Asp Asp Lys Pro Leu Phe Asn
465 470 475 480
Leu Gly Ala Val Tyr Lys Leu Thr Asp Ala Gln Gln Val Tyr Ala Asn
485 490 495
Phe Ser Gln Gly Phe Ser Phe Pro Asp Val Gln Arg Met Leu Arg Asp
500 505 510
Val Ser Thr Tyr Thr Val Ser Thr Ala Asn Leu Gln Pro Ile Thr Val
515 520 525
Asn Ser Tyr Glu Leu Gly Trp Arg Leu Asn Gln Asp Asp Gly Leu Asn
530 535 540
Leu Gly Leu Thr Gly Phe Tyr Asn Thr Ser Asp Lys Thr Val Gln Phe
545 550 555 560
Asn Asn Arg Ala Ala Lys Val Val Asp Thr Asp Gln Arg Val Tyr Gly
565 570 575
Ala Glu Ala Thr Ile Ser Tyr Pro Phe Met Glu Asn Tyr Lys Val Gly
580 585 590
Gly Thr Leu Gly Tyr Thr Arg Gly Gln Tyr Lys Asp Val Ala Asn Lys
595 600 605
Trp His Glu Leu Asn Ser Phe Thr Val Ala Pro Val Lys Gly Thr Leu
610 615 620
Phe Ala Glu Trp Asp Asn Asn Glu Gly Tyr Gly Val Arg Val Gln Met
625 630 635 640
Gln Ala Ile Lys Gly Thr Asn Lys Ala Tyr Lys Asp Asp Arg Glu Leu
645 650 655
Ala Ala Phe Ala Thr Thr Gln Asp Glu Ala Phe Gln Asn Ala Val Lys
660 665 670
Asn Asp Ala Asn Ser Ala Ala Gln Ile Lys Gly Tyr Thr Thr Met Asp
675 680 685
Val Leu Ala His Phe Pro Ala Trp Lys Gly Arg Val Asp Phe Gly Val
690 695 700
Tyr Asn Val Trp Asn Arg Gln Tyr Arg Thr Val Phe Ala Gln Gln Ala
705 710 715 720
Ala Val Ser Asn Ala Asn Pro Leu Leu Ala Ile Pro Ala Glu Gly Arg
725 730 735
Thr Tyr Gly Leu Ser Tyr Thr Phe Asn Tyr
740 745
<210> 48
<211> 476
<212> PRT
<213> Acinetobacter baumannii
<400> 48
Met Gly Ala Gln Leu Val Arg Glu Val Ser Ser Lys Thr Asn Asp Ile
1 5 10 15
Ala Gly Asp Gly Thr Thr Thr Ala Thr Val Leu Ala Gln Ala Ile Leu
20 25 30
Asn Glu Gly Ile Lys Ser Val Thr Ala Gly Met Asn Pro Met Asp Leu
35 40 45
Lys Arg Gly Ile Asp Ile Ala Val Lys Thr Val Val Glu Asn Ile Arg
50 55 60
Ser Ile Ala Lys Pro Ala Asp Asp Phe Lys Ala Ile Glu Gln Val Gly
65 70 75 80
Ser Ile Ser Ala Asn Ser Asp Thr Thr Val Gly Lys Leu Ile Ala Gln
85 90 95
Ala Met Glu Lys Val Gly Lys Glu Gly Val Ile Thr Val Glu Glu Gly
100 105 110
Ser Gly Phe Glu Asp Ala Leu Asp Val Val Glu Gly Met Gln Phe Asp
115 120 125
Arg Gly Tyr Ile Ser Pro Tyr Phe Ala Asn Lys Gln Asp Thr Leu Thr
130 135 140
Ala Glu Leu Glu Asn Pro Phe Ile Leu Leu Val Asp Lys Lys Ile Ser
145 150 155 160
Asn Ile Arg Glu Leu Ile Ser Val Leu Glu Ala Val Ala Lys Thr Gly
165 170 175
Lys Pro Leu Leu Ile Ile Ala Glu Asp Val Glu Gly Glu Ala Leu Ala
180 185 190
Thr Leu Val Val Asn Asn Met Arg Gly Ile Ile Lys Val Cys Ala Val
195 200 205
Lys Ala Pro Gly Phe Gly Asp Arg Arg Lys Ala Met Leu Gln Asp Ile
210 215 220
Ala Ile Leu Thr Gly Ala Thr Val Ile Ser Glu Glu Val Gly Met Ser
225 230 235 240
Leu Glu Gln Ala Thr Leu Gln Asp Leu Gly Thr Ala His Lys Ile Thr
245 250 255
Val Ser Lys Glu Asn Thr Val Ile Val Asp Gly Ala Gly Asp Ala Ala
260 265 270
Ala Ile Ala Glu Arg Val Gln Gln Ile Arg Ala Gln Ile Glu Glu Ser
275 280 285
Thr Ser Glu Tyr Asp Arg Glu Lys Leu Gln Glu Arg Val Ala Lys Leu
290 295 300
Ala Gly Gly Val Ala Val Ile Lys Ile Gly Ala Ala Thr Glu Val Glu
305 310 315 320
Met Lys Glu Lys Lys Asp Arg Val Asp Asp Ala Leu His Ala Thr Arg
325 330 335
Ala Ala Val Glu Glu Gly Val Val Ala Gly Gly Gly Val Ala Leu Val
340 345 350
Arg Ala Val Asn Ala Leu Glu Gly Leu Lys Gly Ala Asn Glu Asp Gln
355 360 365
Thr Ala Gly Ile Asn Ile Leu Arg Arg Ala Ile Glu Ala Pro Leu Arg
370 375 380
Gln Ile Val Ala Asn Ala Gly Asp Glu Pro Ser Val Val Ile Asn Ala
385 390 395 400
Val Lys Asn Gly Glu Gly Asn Phe Gly Tyr Asn Ala Ala Thr Gly Glu
405 410 415
Tyr Gly Asp Met Leu Glu Met Gly Ile Leu Asp Pro Ala Lys Val Thr
420 425 430
Arg Ser Ala Leu Glu His Ala Ala Ser Val Ala Gly Leu Met Leu Thr
435 440 445
Thr Glu Cys Met Ile Thr Asp Ile Pro Glu Asp Lys Pro Ala Ala Pro
450 455 460
Asp Met Gly Gly Met Gly Gly Met Gly Gly Met Met
465 470 475
<210> 49
<211> 472
<212> PRT
<213> Acinetobacter baumannii
<400> 49
Met Ser Ala Phe Phe Gln Pro Gly Asn Tyr Phe Glu Ala Gly Ile Ser
1 5 10 15
Val Leu Asp Pro Asp Val Ala Gly Lys Glu Ala Gly Ser Ser Ala Thr
20 25 30
Arg Arg Asp Ile Gly Asp Met Ala Asn Asp Tyr Tyr Phe Pro Ser Ala
35 40 45
Ala Leu Lys Leu Gln Ile Asn Asp Gln Phe Ser Phe Gly Leu Leu Tyr
50 55 60
Asp Gln Pro Phe Gly Ala Asp Ala Glu Tyr Ser Gly Asn Asn Val Phe
65 70 75 80
Val Ser Asn Pro Gly Ser Asp Thr Ile Leu Ser Gln Lys Ala Leu Gly
85 90 95
Asp Leu Ala Thr Ser Ser Ile Gln Lys Leu Val Gln Ala Ser Gly Ser
100 105 110
Ala Phe Thr Pro Ala Leu Ile Glu Val Thr Lys Val Thr Gly Gly Asp
115 120 125
Pro Thr Lys Pro Thr Gln Thr Glu Ile Leu Gly Ala Leu Gln Gln Val
130 135 140
Ala Ala Gly Gly Asn Thr Thr Val Gly Ala Gly Leu Thr Ala Leu Gln
145 150 155 160
Lys Thr Gln Ala Ala Ile Asn Ala Ala Asn Asn Tyr Leu Gly Thr Gly
165 170 175
Gly Thr Lys Val Lys Val Asp Thr Gln Asn Leu Ser Phe Val Phe Gly
180 185 190
Tyr Gln Pro Thr Lys Asn Phe Asn Phe Tyr Ala Gly Pro Val Leu Gln
195 200 205
Thr Val Lys Gly Asn Val Ser Leu Arg Gly Gln Ala Tyr Ser Leu Tyr
210 215 220
Asn Gly Tyr Asp Ala Asn Ile Lys Glu Thr Thr Gly Ala Gly Trp Leu
225 230 235 240
Ala Gly Ala Ala Tyr Gln Ile Pro Glu Ile Ala Leu Arg Ala Ser Val
245 250 255
Thr Tyr Arg Ser Glu Ile Asp His Lys Val Asn Ile Asp Glu Asn Leu
260 265 270
Ser Ile Leu Asn Phe Pro Gly Leu Thr Ser Val Leu Ala Gly Leu Asp
275 280 285
Val Pro Ala Ser Lys Leu Gln Ala Ile Asn Ser Ser Gly Lys Thr Thr
290 295 300
Ile Thr Thr Pro Gln Ser Val Asn Leu Asp Phe Gln Thr Gly Ile Met
305 310 315 320
Ala Asp Thr Val Ala Phe Ala Asn Val Arg Trp Val Asn Trp Lys Asp
325 330 335
Phe Ser Ile Gln Pro Tyr Lys Phe Gly Lys Val Ser Glu Ala Val Gly
340 345 350
Gly Leu Ile Gly Arg Pro Asn Gly Phe Asn Leu Val Glu Tyr Ser Asp
355 360 365
Asp Gln Trp Ser Val Asn Ala Gly Val Gly Arg Lys Leu Asn Asp Lys
370 375 380
Trp Ala Gly Asn Val Ser Val Gly Trp Asp Ser Gly Ala Gly Asn Pro
385 390 395 400
Val Thr Thr Leu Gly Pro Thr Glu Gly Tyr Trp Asn Val Gly Leu Gly
405 410 415
Val Gln Tyr Ser Pro Thr Pro Gln Thr Phe Ile Ala Gly Gly Val Lys
420 425 430
Tyr Phe Trp Leu Gly Asp Ala Lys Ala Gln Thr Gly Ala Gln Ala Gly
435 440 445
Ser Asp Glu Tyr Val Ala Asp Phe Ser Asp Asn Asn Ala Ile Ala Tyr
450 455 460
Gly Leu Lys Leu Gly Tyr Lys Phe
465 470
<210> 50
<211> 216
<212> PRT
<213> Acinetobacter baumannii
<400> 50
Met Val Phe Ala Gln Asp Asp Asn Ala Leu His Tyr Asn Ile Val Asn
1 5 10 15
Val Gln Ala Glu Ala Ser Arg Gln Val Ser Asn Asp Glu Met His Ala
20 25 30
Thr Leu Tyr Ile Glu Lys Ser Asn Lys Gln Pro Ala Glu Leu Ser Asn
35 40 45
Gln Ile Asn Gln Leu Met Asn Gln Ala Leu Ala Thr Ser Arg Lys Tyr
50 55 60
Pro Gln Val Lys Val Glu Thr Gly Ala Gln Ser Thr Tyr Pro Ile Tyr
65 70 75 80
Asp Asn Asp Ser Asn Lys Leu Lys Glu Trp Arg Gly Arg Ala Glu Ile
85 90 95
Arg Leu Glu Ser Lys Asp Phe Lys Ala Ala Ser Gln Leu Ile Asn Glu
100 105 110
Leu Gln Gln Ser Phe Gln Thr Gln Ser Ile Asn Phe Ser Val Ser Asp
115 120 125
Glu Gln Arg Lys Lys Val Glu Asn Glu Leu Met Val Glu Ala Ser Lys
130 135 140
Asn Phe Gln Gln Arg Ala Gln Met Leu Thr Gln Ala Trp Asn Lys Ser
145 150 155 160
Gln Tyr Ser Leu Val Thr Leu Asn Leu Asn Thr Asn Asn Tyr Phe Pro
165 170 175
Gln Pro Val Met Arg Ala Ser Leu Ala Lys Phe Ala Ala Ala Glu Ala
180 185 190
Ala Pro Ala Gln Asp Met Ala Ala Gly Glu Ser Lys Ile Thr Val Asn
195 200 205
Ala Asn Gly Ser Ile Gln Phe Lys
210 215
<210> 51
<211> 366
<212> PRT
<213> Acinetobacter baumannii
<400> 51
Met Lys Tyr Cys Gln Phe Phe Ser Val Leu Ala Leu Ser Leu Ser Ala
1 5 10 15
Ala Ser Cys Ala Val Thr Ser Gly Leu Gln Thr Tyr Asp Ile Pro Ser
20 25 30
Glu Gly Val Tyr Lys Thr Asp Leu Gly Thr Thr Val Asn Val Val Lys
35 40 45
Ile Ser Gln Glu Thr Leu Pro Ala Ile Gln Pro Ala Gln Ile Asp Tyr
50 55 60
Gln Arg Asp Tyr Ala Ser Leu Phe Lys Asn Gln Gln Ser Ile Tyr Arg
65 70 75 80
Leu Ser Pro Gly Asp Val Leu Ser Ile Gln Leu Trp Ala Tyr Pro Glu
85 90 95
Ile Thr Pro Pro Val Asn Asn Ile Ser Asn Glu Gln Ser Ile Gln Ala
100 105 110
Asn Gly Tyr Pro Ile Asp Gln Ser Gly Tyr Ile Gln Phe Pro Leu Val
115 120 125
Gly Arg Tyr Lys Ala Ala Gly Lys Thr Leu Ala Gln Val Asn Arg Glu
130 135 140
Leu His Ser Gln Leu Ala Arg Phe Leu Lys Asn Pro Asp Val Val Val
145 150 155 160
Arg Val Val Ser Tyr Glu Gly Gln Arg Phe Ser Val Gln Gly Ser Val
165 170 175
Thr Lys Gly Gly Gln Phe Tyr Leu Ser Asp Gln Pro Val Ser Ile Tyr
180 185 190
Thr Ala Leu Gly Met Ala Gly Gly Val Thr Thr Thr Gly Asp Asn Thr
195 200 205
Tyr Ile Gln Leu Ile Arg Asn Gly Arg Thr Tyr Asn Leu Asn Thr Ile
210 215 220
Asp Leu Glu Lys Ala Gly Tyr Ser Leu His Lys Leu Leu Val Gln Pro
225 230 235 240
Asn Asp Thr Ile Tyr Val Ser Thr Arg Glu Asn Gln Lys Ile Tyr Val
245 250 255
Met Gly Glu Ser Gly Lys Asn Gln Ala Leu Pro Met Arg Asp Gln Gly
260 265 270
Met Thr Leu Ser Asp Ala Leu Gly Glu Ser Leu Gly Ile Asn Pro Asn
275 280 285
Ser Ala Ser Ala Ser Arg Ile Tyr Val Val Arg Thr Asn Pro Asn Asp
290 295 300
Arg Thr Thr Glu Ile Tyr His Leu Asn Leu Met Ser Leu Gly Asp Phe
305 310 315 320
Gly Leu Ala Asn Gln Phe Arg Leu Arg Ser Asn Asp Ile Val Tyr Ile
325 330 335
Asp Ala Thr Gly Leu Thr Arg Trp Gln Arg Val Val Asn Gln Ile Ile
340 345 350
Pro Phe Ser Asn Ala Leu Tyr Asn Ile Asp Arg Leu Gly Gln
355 360 365
<210> 52
<211> 208
<212> PRT
<213> Acinetobacter baumannii
<400> 52
Met Leu Asp Arg His Val Leu Arg Pro Val Ala Val Glu Tyr Arg Glu
1 5 10 15
Lys Thr Pro Glu Asp Val Arg Gly Ser Tyr Arg Gln Phe Arg Lys Asn
20 25 30
Leu Gly Glu Pro Trp Asn Ala Val Asn Gln Leu Ile Gln Gly Arg Pro
35 40 45
Gly Arg Ala Ala Lys Thr Leu Gly Arg Phe Thr Ile Asn Thr Leu Thr
50 55 60
Thr Leu Gly Leu Ala Asp Pro Ala Ser Arg Leu Gly Leu Pro Pro Glu
65 70 75 80
Glu Glu Ser Phe Gly Val Thr Leu Gly Tyr Tyr Gly Val Pro Ser Gly
85 90 95
Pro Phe Leu Met Leu Pro Phe Phe Gly Pro Ser Thr Leu Arg Asp Gly
100 105 110
Val Gly Leu Ala Val Asp Ala Gln Ala Arg Pro Gln Lys Tyr Ile Met
115 120 125
Asp Asp Gln Asp Gly Leu Tyr Trp Ser Thr Asn Leu Leu Gln Ala Val
130 135 140
Asp Thr Arg Ala Gln Tyr Leu Asp Leu Asp Gln Thr Ile Gln Gly Asp
145 150 155 160
Gln Tyr Ala Met Ile Arg Asp Leu Tyr Leu Gln Arg Lys Ala Phe Gln
165 170 175
Ile Ala Glu Lys Lys Gly Asp Ser Ala Asp Val Ser Phe Ile Asp Asp
180 185 190
Asp Glu Ser Glu Asp Val Pro Glu Asp Asn Thr Asp Lys Thr Glu Lys
195 200 205
<210> 53
<211> 326
<212> PRT
<213> Acinetobacter baumannii
<400> 53
Met Val Leu Leu Asn Ser Lys Gly Pro Val Gly Gln Gly Gln Ser Asp
1 5 10 15
Leu Met Met Thr Ala Ile Tyr Leu Met Leu Leu Val Val Ile Pro Ser
20 25 30
Ile Ile Met Ala Leu Trp Phe Gly Trp Lys Tyr Arg Ala Ser Asn Lys
35 40 45
Asp Ala Asp Tyr Lys Pro Thr Trp Ala His Ser Thr Ala Ile Glu Val
50 55 60
Val Val Trp Gly Ile Pro Val Ile Ile Ile Gly Ile Leu Ala Trp Leu
65 70 75 80
Thr Trp Trp Gly Ser His Lys Tyr Asp Pro Tyr Arg Pro Leu Glu Ser
85 90 95
Asp Lys Ala Pro Leu Thr Ile Gln Val Ile Ala Glu Gln Phe Lys Trp
100 105 110
Ile Phe Ile Tyr Pro Glu Gln Asn Ile Ala Thr Val Asn Glu Val Arg
115 120 125
Phe Pro Glu Lys Thr Pro Leu Ser Phe Lys Ile Thr Ser Asn Phe Thr
130 135 140
Met Asn Ser Phe Phe Ile Pro Gln Leu Gly Gly Gln Ile Tyr Ala Met
145 150 155 160
Ala Gly Met Gln Thr His Leu His Leu Leu Ala Asn Glu Thr Gly Val
165 170 175
Tyr Arg Gly Phe Ser Ser Asn Tyr Ser Gly Tyr Gly Phe Ser Gln Met
180 185 190
Arg Phe Lys Ala His Ser Val Thr Glu Gln Gln Phe Asn Glu Trp Val
195 200 205
Ala Ala Val Lys Ala Gly Asn Gly Thr Thr Ile Asn Pro Glu Ala Val
210 215 220
Gln Lys Thr Thr Leu Asp Gln Ala Glu Leu Ala Thr Leu Arg Asp Gly
225 230 235 240
Asp Arg Ser Lys His Gln Ile Glu His Leu Val Asn Arg Ala Lys Ala
245 250 255
Ala Gly Asp Gln Glu Ala Leu Ala Lys Ala Glu Ala Met Lys Pro Phe
260 265 270
Pro Thr Lys Pro His Pro Val Thr Tyr Tyr Ser Ser Val Glu Pro Lys
275 280 285
Leu Phe Glu Thr Ile Ile Asn His Tyr Met Ser Asn Tyr His Gly Ala
290 295 300
Asp His Ser Ala Ala His Thr Ala Ala Glu Thr His Val Ala Ala Glu
305 310 315 320
His Ala Ala Gln Gly Glu
325
<210> 54
<211> 207
<212> PRT
<213> Acinetobacter baumannii
<400> 54
Met Ala Arg Tyr Ile Gly Pro Lys Cys Lys Leu Ser Arg Arg Glu Gly
1 5 10 15
Thr Asp Leu Gln Leu Lys Ser Gly Val Lys Pro Phe Asp Val Lys Thr
20 25 30
Lys Lys His Ala Lys Ala Pro Gly Gln His Gly Gln Ala Arg Gly Lys
35 40 45
Gln Ser Glu Tyr Ser Leu Gln Leu Arg Glu Lys Gln Lys Val Arg Arg
50 55 60
Met Tyr Gly Val Leu Glu Arg Gln Phe Ser Asn Tyr Tyr Lys Glu Ala
65 70 75 80
Ala Arg Val Lys Gly Ala Thr Gly Glu Asn Leu Leu Lys Leu Leu Glu
85 90 95
Ser Arg Leu Asp Asn Val Val Tyr Arg Met Gly Phe Gly Ser Thr Arg
100 105 110
Ala Glu Ala Arg Gln Leu Val Ser His Arg Ser Ile Thr Leu Asn Gly
115 120 125
Arg Arg Val Asn Ile Ala Ser Ile Gln Val Lys Ala Gly Asp Val Ile
130 135 140
Ala Val His Glu Gly Ala Lys Gln Gln Leu Arg Ile Lys Asn Ala Ile
145 150 155 160
Glu Leu Ala Ala Gln Arg Gly Ile Pro Ala Trp Met Asp Val Asp His
165 170 175
Ser Lys Leu Glu Gly Thr Phe Lys Ala Ala Pro Asp Arg Ser Asp Leu
180 185 190
Pro Ala Glu Ile Asn Glu Ser Leu Ile Val Glu Leu Tyr Ser Lys
195 200 205
<210> 55
<211> 355
<212> PRT
<213> Acinetobacter baumannii
<400> 55
Met Ala His Ala Glu Val Asn Ser Ser Ser Thr Gln Gln Val Asn Gly
1 5 10 15
Leu Ser Ser Gly Ala Gln Ala Glu Glu Asn Lys Asp Glu Asn Leu Leu
20 25 30
Asp Gln Ile Pro Arg Trp Ile Asp Ala Thr Pro Thr Ile Phe Pro Glu
35 40 45
Gln Ser Asn Glu Pro Ile Val Pro Pro Thr Glu Gln Thr Glu Asp Gln
50 55 60
Thr Trp Phe Asp Arg Lys Gln Lys Lys Ile Arg Asn Trp Ala Asp Arg
65 70 75 80
Thr Ser Gly Lys Ile Asp Asn Trp Phe Gly Glu Val Asp Pro Gln Lys
85 90 95
Pro Ala Ser Ala Thr Ile Arg Val Met Ile Asp Asn Tyr Trp Asn Glu
100 105 110
Tyr Asp Asn Tyr Glu Ile Lys Pro Arg Ile Arg Gly Lys Ile Lys Leu
115 120 125
Pro Thr Leu Glu Lys Arg Leu Ser Val Val Phe Gly Asp Asp Ser Leu
130 135 140
Asp Asp Glu Phe Asn Asn Ser Pro Ala Asn Ile Asn Gln Asn Pro Asn
145 150 155 160
Gln Asp Pro Asn Lys Lys Leu Asp Gly Lys Arg Thr Arg Asp Asp Asn
165 170 175
Ser Ser Ile Ala Leu Arg Trp Ser Asn Phe Ser Lys Lys Leu Pro Phe
180 185 190
Glu Thr Asp Ala Asp Leu Gly Ile Arg Ser Gly Asp Asp Ile Tyr Val
195 200 205
Arg Leu Lys Ala Ser Arg Asp Trp Gln Leu Arg Asn Asp Phe Lys Phe
210 215 220
Tyr Ala Glu Gln Ile Tyr Arg Tyr Gly Ile Asp Ser Glu Asn Tyr Leu
225 230 235 240
Arg Thr Asn Leu Glu Leu Thr His Ala Arg Pro Asn Gln Pro Ile Leu
245 250 255
Ser Asn Gln Phe Ser Leu Thr Tyr Ala Asp Asp Gln Asp Asp Asp Leu
260 265 270
Thr Trp Glu Asn Arg Leu Phe Arg Glu His Ser Phe Phe Ala Asn Asn
275 280 285
Arg Phe Asn Tyr Gly Ile Tyr Thr Gly Gly Tyr Tyr Asn Asp Asn Asp
290 295 300
Leu Arg Leu Asn Ser Trp Gly Pro Phe Val Ser Trp Arg Gln Pro Val
305 310 315 320
Leu Arg Glu Trp Phe Phe Val Gln Gly Asp Leu Asn Tyr Phe Asn Asp
325 330 335
His Arg Glu Asp Arg Asn His Tyr Val Ser Thr Phe Leu Arg Leu Glu
340 345 350
Ala Leu Phe
355
<210> 56
<211> 108
<212> PRT
<213> Acinetobacter baumannii
<400> 56
Met Ser Thr Leu Leu Val Ala Cys Asn Lys His Glu Asn Lys Thr Glu
1 5 10 15
Thr Thr Ser Asp Ala Ser Thr Pro Val Gln Thr Ala Gln Ser Asn Asn
20 25 30
Asn Glu Ala Val Asp Thr Ala His Thr Ala Glu Asn Ser Leu Asp Trp
35 40 45
Asp Gly Lys Tyr Lys Gly Thr Leu Pro Cys Ala Asp Cys Glu Gly Ile
50 55 60
Lys Thr Glu Leu Glu Leu Lys Asp Asp Lys Thr Tyr Glu Leu Thr Glu
65 70 75 80
Thr Tyr Leu Gly Lys Gly Asp Ala Asn Pro Phe Glu Pro Met Val Ser
85 90 95
Leu Leu Ser Ile Lys Thr Ile Leu Leu Leu Leu Pro
100 105
<210> 57
<211> 635
<212> PRT
<213> Acinetobacter baumannii
<400> 57
Met Arg Gly Phe Gly Ala Arg Ser Thr Phe Gly Val Arg Gly Ile Arg
1 5 10 15
Leu Tyr Val Asp Gly Ile Pro Ala Thr Met Pro Asp Gly Gln Gly Gln
20 25 30
Thr Ser Asn Ile Asp Leu Ser Ser Leu Asp His Val Glu Val Leu Thr
35 40 45
Gly Pro Phe Ser Ser Leu Tyr Gly Asn Ser Ser Gly Gly Thr Ile Leu
50 55 60
Thr Ser Thr Lys Glu Gly Gln Gly Lys Asp Ser Ile Glu Leu Ser Tyr
65 70 75 80
Ser Gly Gly Ser His Asp Lys Ser Arg Ala Gly Leu Val Leu Gln Gly
85 90 95
Gly Ala Lys Gly Ala Asn Glu Pro Ser Tyr Ile Ile Ser Ser Ser Tyr
100 105 110
Phe Asp Thr Asp Gly Tyr Arg Glu His Ser Gly Ala Glu Lys Val Leu
115 120 125
Asn Asn Ala Lys Leu Ser Trp Asn Leu Asp Asp Gly Ser Lys Ile Asn
130 135 140
Trp Val Thr Asn Tyr Val Lys Ile His Ala Asp Asp Pro Met Gly Leu
145 150 155 160
Glu Arg Lys Asp Trp Gln Ala Asn Pro Lys Gln Ile Ala Pro Tyr Val
165 170 175
Lys Lys Trp Gly Phe Asn Ala Arg Lys Asp Ile Glu Gln Thr Gln Thr
180 185 190
Gly Ile Thr Trp Phe Lys Pro Ile Asn Asp Gln His Glu Leu Tyr Ala
195 200 205
Met Ala Tyr Leu Gly Asn Arg Gln Val Thr Gln Tyr Gln Ser Ile Pro
210 215 220
Gln Gly Gln Val Val Val Glu Asn Gly Lys Pro Val Tyr Thr Gly Gln
225 230 235 240
Lys Ser Pro Lys His Ala Gly Gly Val Ile Asp Phe Glu Arg Asn Tyr
245 250 255
Tyr Gly Ala Asp Phe Arg Trp Thr Gly Lys Glu Leu Leu Pro Asn Thr
260 265 270
Thr Val Ser Ile Gly Val Ala Phe Asp Ala Met Asp Glu Glu Arg Lys
275 280 285
Gly Phe Glu Asn Phe Asn Ala Asp Gly Ile Tyr Gly Val Lys Gly Asn
290 295 300
Leu Arg Arg Asp Glu Asp Asn Thr Leu Trp Asn Ile Asp Pro Tyr Leu
305 310 315 320
Gln Ala Ser Trp Gln Phe Leu Pro Thr Trp Arg Leu Asp Thr Gly Val
325 330 335
Arg Tyr Ser Asn Val His Tyr Lys Ser Lys Asp His Phe Thr Ser Gly
340 345 350
Pro Asp Glu Tyr Gly Thr Val Asn Gly Asp Asp Ser Gly Lys Thr Asp
355 360 365
Tyr Glu Lys Val Leu Pro Ser Ala Ala Leu Ser Trp Gln Ile Leu Pro
370 375 380
Glu Leu Met Ala Tyr Val Ser Tyr Ala Lys Gly Phe Glu Thr Pro Thr
385 390 395 400
Phe Thr Glu Met Ala Tyr His Thr Asp Ile Ser Lys Ser Gly Phe Asn
405 410 415
Phe Gly Leu Lys Pro Ser Thr Ser Asp Thr Tyr Glu Thr Gly Leu Lys
420 425 430
Ser Gln Asn Leu Leu Gly Asp Phe Thr Leu Ala Val Phe Gln Thr Lys
435 440 445
Thr Lys Asn Asp Ile Val Ser Ala Gly Asn Leu Gly Gly Arg Ser Thr
450 455 460
Phe Arg Asn Ala Asp Lys Thr Leu Arg Glu Gly Val Glu Phe Ala Trp
465 470 475 480
Asn Lys Lys Leu Trp Arg Asp Leu Thr Ala Thr Ala Ser Tyr Thr Tyr
485 490 495
Leu Asp Ala Thr Phe Asp Ala Asn Val Pro Glu Lys Leu Asp Gln Asp
500 505 510
Asn Lys Val Leu Ala Ser Ala Ile Pro Thr Gly Asn Ala Ile Pro Gly
515 520 525
Ile Ala Lys Asn Gln Ala Tyr Ala Ser Leu Ala Trp Gln Pro Ser His
530 535 540
Gly Leu Tyr Gly Gly Val Asp Val Gln Tyr Met Asp Lys Val Tyr Val
545 550 555 560
Asn Asp Thr Asn Ser Asp Ala Ala Pro Ser Tyr Ser Val Thr Ser Ala
565 570 575
Asn Val Gly Tyr Ala Trp Val Met Gly Asp Trp Lys Val Asn Ser Phe
580 585 590
Ala Arg Val Asp Asn Leu Phe Asp Lys Lys Tyr Ala Gly Ser Val Ile
595 600 605
Val Asn Asp Gly Asn Ser Arg Tyr Phe Glu Pro Ala Asp Gly Arg Asn
610 615 620
Trp Ser Ala Gly Leu Arg Val Ile Lys Gln Phe
625 630 635
<210> 58
<211> 381
<212> PRT
<213> Acinetobacter baumannii
<400> 58
Met Thr Gly Ile Ser Ser Val Tyr Ala Gln Glu Gln Val Asp Pro Ala
1 5 10 15
Tyr Lys Pro Gly Asn Pro Ile Tyr Asp Lys Trp Asp Arg Phe Tyr Lys
20 25 30
Ile Glu Gln Ser Gln Pro Gln Glu Ala Glu Lys Ile Leu Val Glu Leu
35 40 45
Ser Lys Leu Thr Pro Thr Asp Ile Lys Val Trp Lys Ser Leu Thr Tyr
50 55 60
Leu Gln Ile Arg Leu Glu Lys Arg Glu Glu Ala Leu Gln Ser Leu Arg
65 70 75 80
Gln Ala Arg Asn Leu Ala Pro Gln Asp Asp Thr Leu Lys Leu Gln Glu
85 90 95
Ala Tyr Leu Leu Asn Gln Gln Lys Lys Asp Arg Glu Ala Leu Val Leu
100 105 110
Phe Lys Glu Leu Ser Ser Ser Ser Asp Pro Glu Ile Ala Ala Lys Ala
115 120 125
Thr Gln Ala Val Lys Asn Leu Ser Gly Gly Glu Val Lys Pro Tyr Phe
130 135 140
Lys Asp Ile Tyr Phe Ala Pro Ser Tyr Glu Ser Arg Tyr Asp Asp Val
145 150 155 160
Ile Phe Pro Leu Lys Met Arg Tyr Gly Lys Asn Ile Asp Asn Gly Arg
165 170 175
Ala Gln Val Tyr Ala Phe Leu Asn Leu Asn Arg Asp Thr Gln Ser Gln
180 185 190
Gly Gly Val Arg Pro Glu Ile Ile Asp Glu Asn Ala Ala Thr Leu Gly
195 200 205
Leu Gly Ala Asn Tyr Gln Pro Trp Thr Ser Ile Pro Val Arg Ala Tyr
210 215 220
Val Glu Val Gly Gly Ser Tyr Asp Leu Ile Asp Arg Asn Arg Lys Arg
225 230 235 240
Phe Arg Glu Ser Val Val Gly Gly Val Thr Gly Tyr Gln Glu Trp Tyr
245 250 255
Ser Gln Ser Asn Cys Asp His Ser Leu Cys Leu Asp Asn Tyr Phe Thr
260 265 270
Asp Leu Tyr Gly Asn Val Ala Thr Tyr Ser Arg Glu Asp Tyr Asn Val
275 280 285
Ile Gly Asp Leu Arg Leu Arg Thr Gly Leu Asn Leu Tyr Lys Gly Glu
290 295 300
Ser Gly Thr Val Gln Ala Tyr Val Lys Leu His Gly Leu Ala Asp Ser
305 310 315 320
Glu Asp Glu Tyr Tyr Asn Asn Leu Phe Glu Tyr Gly Pro Gly Ile Ser
325 330 335
Trp Gln Pro Phe Asn Tyr Gln Pro Ile Lys Leu Arg Val Glu Arg Leu
340 345 350
Tyr Gly Asn Tyr Phe Lys Asp Val Pro Val Asn Thr Lys Asp His Tyr
355 360 365
Asn Asn Thr Arg Val Glu Leu Val Phe Tyr Lys Asp Phe
370 375 380
<210> 59
<211> 212
<212> PRT
<213> Acinetobacter baumannii
<400> 59
Met Ala Ile Gly Leu Val Gly Arg Lys Cys Gly Met Thr Arg Ile Phe
1 5 10 15
Thr Asp Ala Gly Val Ser Val Pro Val Thr Val Ile Glu Val Asp Pro
20 25 30
Asn Arg Ile Thr Gln Ile Lys Thr Leu Glu Thr Asp Gly Tyr Gln Ala
35 40 45
Val Gln Val Thr Thr Gly Glu Arg Arg Glu Ser Arg Val Thr Asn Ala
50 55 60
Gln Lys Gly His Phe Ala Lys Ala Gly Val Ala Ala Gly Arg Leu Val
65 70 75 80
Lys Glu Phe Arg Val Thr Glu Ala Glu Leu Glu Gly Arg Glu Ile Gly
85 90 95
Gly Thr Ile Gly Val Asp Leu Phe Thr Val Gly Gln Val Val Asp Val
100 105 110
Thr Gly Gln Ser Lys Gly Lys Gly Phe Gln Gly Gly Val Lys Arg Trp
115 120 125
Asn Phe Arg Thr Gln Asp Ala Thr His Gly Asn Ser Val Ser His Arg
130 135 140
Val Leu Gly Ser Thr Gly Gln Asn Gln Thr Pro Gly Arg Val Phe Lys
145 150 155 160
Gly Lys Lys Met Ala Gly His Leu Gly Asp Glu Arg Val Thr Val Gln
165 170 175
Gly Leu Glu Ile Val Ser Ile Asp Ala Glu Arg Ser Val Leu Val Val
180 185 190
Lys Gly Ala Ile Pro Gly Ala Thr Gly Gly Asp Val Ile Val Arg Pro
195 200 205
Thr Ile Lys Ala
210
<210> 60
<211> 424
<212> PRT
<213> Acinetobacter baumannii
<400> 60
Met Leu Lys Ala Gln Lys Leu Thr Leu Ala Val Leu Ile Ser Ala Ala
1 5 10 15
Ile Ile Ser Ser Ala Gln Ala Ser Glu Gln Ser Glu Ala Lys Gly Phe
20 25 30
Val Glu Asp Ala Asn Gly Ser Ile Leu Phe Arg Thr Gly Tyr Ile Ser
35 40 45
Arg Asp Lys Lys Asp Gly Arg Ala Asp Asn Ser Ser Phe Ala Gln Thr
50 55 60
Ala Ile Val Asn Ile Asp Ser Gly Phe Thr Pro Gly Ile Val Gly Phe
65 70 75 80
Gly Val Gly Val Val Gly Asp Gly Ser Phe Lys Ile Gly Glu Asn Lys
85 90 95
Asn Ala Gly Asn Asn Met Ile Pro Gln His Asn Asp Gly Ser Ala Tyr
100 105 110
Asp His Trp Ala Arg Gly Gly Ala Asn Val Lys Ala Arg Phe Ser Asn
115 120 125
Thr Thr Val Arg Tyr Gly Thr Gln Val Leu Asp Leu Pro Val Leu Ala
130 135 140
Ser Asn Thr Ala Arg Leu Val Pro Glu Tyr Phe Thr Gly Thr Leu Leu
145 150 155 160
Thr Ser His Glu Ile Lys Asp Leu Glu Val Val Ala Gly Lys Phe Thr
165 170 175
Lys Asn Gln Tyr Ser Asp Gln Ile Ala Thr Asp Gln Asn Gly Leu Asp
180 185 190
Arg Ala Val Val Trp Gly Ala Lys Tyr Lys Phe Asp Asp Gln Ile Ser
195 200 205
Gly Ser Tyr Tyr Gly Val Asp Val Lys Asp Lys Leu Asp Arg His Tyr
210 215 220
Val Asn Val Asn Tyr Lys Gln Pro Leu Ala Asn Asp Ser Ser Leu Thr
225 230 235 240
Tyr Asp Phe Ser Gly Tyr His Thr Lys Phe Asp Lys Gly Ala Asn Leu
245 250 255
Ser Tyr Ala Thr Gly Pro Ala Asp Glu Asp Lys Thr Asn Asn Ile Trp
260 265 270
Ala Ile Ser Gly Thr Tyr Ala Thr Gly Pro His Ser Val Met Leu Ala
275 280 285
Tyr Gln Gln Asn Ser Gly Asn Ile Gly Tyr Asn Tyr Gly Val Asn Gln
290 295 300
Asp Gly Gly Gln Ser Val Tyr Leu Pro Asn Ser Tyr Leu Ser Asp Phe
305 310 315 320
Ile Gly Asn Asp Glu Lys Ser Ala Gln Ile Gln Tyr Ser Leu Asp Phe
325 330 335
Gly Lys Leu Gly Val Leu Pro Gly Leu Asn Trp Thr Thr Ala Tyr Val
340 345 350
Tyr Gly Trp Asp Ile Lys Thr Ser Asn Gly Ala Asp Asp Ser Asn Glu
355 360 365
Ser Glu Phe Phe Asn Gln Val Lys Tyr Thr Val Gln Ser Gly Phe Ala
370 375 380
Lys Gly Ser Ser Leu Arg Leu Arg Asn Ser Ile Tyr Arg Ala Asp Asn
385 390 395 400
Ala Tyr Thr Thr Asp Tyr Met Pro Asp Thr Asn Glu Trp Arg Ile Phe
405 410 415
Leu Asp Ile Pro Val Thr Leu Phe
420
<210> 61
<211> 641
<212> PRT
<213> Acinetobacter baumannii
<400> 61
Met Gln Leu Lys Asp Val Pro Gln Ile Val Asn Val Val Pro Lys Gln
1 5 10 15
Val Leu Arg Glu Gln Thr Val Thr Ser Met Gln Gly Ala Leu Gln Asn
20 25 30
Val Ala Gly Leu Ser Phe Ser Val Gly Asp Gly Gln Arg Asp Gln Val
35 40 45
Met Ile Arg Gly Phe Ser Ala Ile Thr Asp Asn Tyr Val Asp Gly Ile
50 55 60
Arg Asp Asp Ala Leu Tyr Phe Arg Asp Met Ser Asn Val Glu Arg Ile
65 70 75 80
Glu Val Leu Lys Gly Pro Ala Ser Val Leu Tyr Gly Arg Gly Ser Ala
85 90 95
Gly Gly Leu Val Asn Lys Ile Asn Lys Lys Pro Met Asp Gln Ser Leu
100 105 110
Arg Glu Val Ser Leu Ile Gly Ser Thr Thr Gly Gln Arg Arg Ala Glu
115 120 125
Val Asp Val Asn Glu Lys Val Ala Glu Asn Val Lys Val Arg Leu Thr
130 135 140
Gly Ala Val Glu Asp Ser Asp Gly Tyr Arg Asp Gln Ala Phe Leu Lys
145 150 155 160
Arg Gln Ala Val Ala Pro Ser Val Gln Trp Asp Ile Thr Asp Lys Thr
165 170 175
Lys Leu Leu Leu Gln Ala Asp Tyr Leu His Asp Asn Arg Leu Ala Asp
180 185 190
Gln Gly Phe Pro Thr Asp Pro Ile Thr Gly Lys Pro Val Lys Thr Asn
195 200 205
Pro Lys Thr Phe Tyr Gly Ala Leu Asn Gly Lys Glu Val Gly Asp Val
210 215 220
Asp Thr Glu Ile Ser Ser Gln Thr Ile Ser Leu Asp His Glu Phe Asn
225 230 235 240
Asp Asn Phe Lys Tyr His Gly Ala Val Arg His Tyr Asn Tyr Ser Leu
245 250 255
Asp Arg Gln Tyr Ser Val Asp Ser His Gln Lys Leu Pro Ala Asp Gln
260 265 270
Ile Gln Leu Thr Gln Asn Lys Arg Leu Arg Asn Glu Asp Gly Val Tyr
275 280 285
Val Gln Gln Glu Leu Ser Ala Val Phe Asn Thr Gly Phe Leu Lys His
290 295 300
Ser Thr Leu Ile Gly Ala Glu Tyr Ser Lys Gln His Lys Asp Glu Leu
305 310 315 320
Val Trp Ser Lys Ala Arg Gln Ile Thr Asn Ile Phe Asn Pro Gln Leu
325 330 335
Glu Asn Trp Ala Pro Leu Asp Thr Asn Val Asp Ala Asp Thr Asn Asn
340 345 350
Thr Asn Thr Phe Glu Asn Tyr Gly Val Tyr Leu Gln Asp Leu Met Thr
355 360 365
Val Thr Asp Gln Leu Lys Val Leu Val Gly Leu Arg Tyr Asp Asn Leu
370 375 380
Ser Gln Asp Arg Asp Asp Lys Thr Ser Lys Asn Val Asp Leu Asn Arg
385 390 395 400
Thr Asp Asn Thr Tyr Ser Pro Arg Ile Gly Val Val Tyr Gln Pro Val
405 410 415
Asn Asn Leu Ser Leu Tyr Thr Ser Tyr Asn Arg Ser Phe Gln Pro Leu
420 425 430
Ala Asp Ser Phe Val Phe Tyr Lys Asn Ser Asp Asp Leu Arg Pro Thr
435 440 445
Lys Thr Glu Asn Tyr Glu Ile Gly Ala Lys Trp Asp Val Asn Asp Gln
450 455 460
Leu Asn Val Thr Leu Ala Leu Phe Glu Met Ser Gln Thr Asn Ile Gln
465 470 475 480
Asn Lys Asp Pro Asn Asp Pro Lys Gly Leu Thr Ala Ile Leu Ala Gly
485 490 495
Glu Gln Lys Thr Lys Gly Val Glu Ile Ser Leu Ala Gly Gln Leu Thr
500 505 510
Asp Gln Leu Ser Val Leu Ala Gly Tyr Ser Tyr Met Asp Gly Lys Ile
515 520 525
Glu Lys Ser Ala Ile Gly Phe Thr Gly Asn His Ser Ala Leu Thr Pro
530 535 540
Asn Asn Thr Ala Asn Leu Trp Leu Lys Tyr Gln Ile Asn Asp His Trp
545 550 555 560
Tyr Ala Ala Val Gly Gly Arg Gly Glu Ser Ser Arg Phe Ser Ala Pro
565 570 575
Asp Asn Lys Asn Val Leu Pro Gly Tyr Ala Val Val Asn Ala Ala Leu
580 585 590
Gly Tyr Gln Ser Glu Arg Tyr Asp Val Asn Leu Asn Leu Asn Asn Leu
595 600 605
Phe Asp Arg Asp Tyr Phe Val Ser Gly His Ser Gly Ala Asn Asp Ser
610 615 620
Asn Met Met Gly Asp Pro Leu Asn Ala Gln Val Ala Leu Arg Tyr Arg
625 630 635 640
Phe
<210> 62
<211> 209
<212> PRT
<213> Acinetobacter baumannii
<400> 62
Met Glu Glu Ala Val Gln Val Leu Asn Ser Leu Pro Ala Ala Lys Phe
1 5 10 15
Lys Glu Ser Leu Asp Ile Ser Val Asn Leu Gly Val Asp Pro Arg Lys
20 25 30
Ser Asp Gln Val Val Arg Gly Ala Thr Thr Leu Pro Ala Gly Thr Gly
35 40 45
Lys Thr Val Arg Val Ala Val Phe Ala Gln Gly Ala Gln Ala Glu Ala
50 55 60
Ala Lys Glu Ala Gly Ala Asp Val Val Gly Phe Asp Asp Leu Ala Glu
65 70 75 80
Ser Ile Gln Gly Gly Asn Leu Asp Phe Asp Val Val Ile Ala Ala Pro
85 90 95
Asp Ala Met Arg Val Val Gly Lys Leu Gly Thr Ile Leu Gly Pro Arg
100 105 110
Gly Leu Met Pro Asn Pro Lys Val Gly Thr Val Thr Pro Asp Val Ala
115 120 125
Gly Ala Val Lys Asn Ala Lys Ser Gly Gln Ala Arg Tyr Arg Val Asp
130 135 140
Lys Ala Gly Ile Ile His Ala Ala Ile Gly Gln Val Gly Phe Asp Ala
145 150 155 160
Ala Ala Ile Arg Gln Asn Val Glu Thr Leu Val Ala Asp Leu Lys Lys
165 170 175
Leu Lys Pro Ala Thr Ser Lys Gly Val Tyr Ile Lys Lys Ile Thr Leu
180 185 190
Ser Ser Thr Met Gly Pro Gly Leu Thr Val Asp Val Asn Asn Val Ser
195 200 205
Asn
<210> 63
<211> 147
<212> PRT
<213> Acinetobacter baumannii
<400> 63
Met Tyr Pro Ala Pro Thr Val Asp Gln Leu Ala Ile Asp His Ala Pro
1 5 10 15
Lys Phe Glu Asn Lys Arg Gly Asn Arg Phe Ala Leu Pro Arg Pro Glu
20 25 30
Pro Leu Gln Thr Asp Thr Thr Ala Asp Ala Ser Ala Gln Thr Gly Ser
35 40 45
Ala Leu Gly Arg Pro Gln Leu Val Thr Asp Gly Asn Lys Asn Pro Leu
50 55 60
Leu Lys Ile Asp Gly Ser Thr Ala Glu Ile Trp Gln Tyr Thr Lys Ala
65 70 75 80
Thr Leu Ser Thr Leu Asn Tyr Asn Val Ile Ala Gln Gly Asn Asn Gln
85 90 95
Ala Thr Ile Lys Val Asn Asp Asn Thr Tyr Val Leu Lys Leu Thr Gly
100 105 110
Val Gly Ser Ser His Ser Leu Ala Leu Phe Asn Pro Asp Asn Thr Phe
115 120 125
Ala Ser Pro Asp Val Ala Ala Glu Val Leu Asn Gln Ile Tyr Gln Asn
130 135 140
Trp Pro Ala
145
<210> 64
<211> 201
<212> PRT
<213> Acinetobacter baumannii
<400> 64
Met Lys Val Ser Gly Leu Val Gly Thr Asn Leu Ser Asp Gly Tyr Thr
1 5 10 15
Met Lys Ala Gln Phe Asp Asn Val Asn Gly Leu Lys Pro Arg Ala Lys
20 25 30
Val Thr Met Ser Gly Val Thr Ile Gly Arg Val Asp Ser Ile Thr Leu
35 40 45
Asp Pro Val Thr Arg Leu Ala Thr Val Thr Phe Asp Leu Asp Gly Lys
50 55 60
Leu Thr Ser Phe Asn Ala Glu Gln Leu Lys Glu Val Gln Lys Asn Ala
65 70 75 80
Leu Asp Glu Leu Arg Tyr Ser Ser Asp Tyr Thr Gln Ala Thr Pro Ala
85 90 95
Gln Gln Lys Thr Met Glu Gln Gln Leu Ile Ser Asn Met Asn Ser Ile
100 105 110
Thr Ser Ile Asp Glu Asp Ala Tyr Ile Met Val Ala Thr Asn Gly Leu
115 120 125
Leu Gly Glu Lys Tyr Leu Lys Ile Val Pro Gly Gly Gly Leu Asn Tyr
130 135 140
Leu Lys Arg Gly Asp Thr Ile Ser Asn Thr Gln Gly Thr Met Asp Leu
145 150 155 160
Glu Asp Leu Ile Ser Lys Phe Ile Thr Gly Gly Gly Ala Gly Lys Val
165 170 175
Ala Ala Gly Ser Ser Ser Ala Glu Glu Lys Ala Pro Ala Ser Thr Asp
180 185 190
Ser Ser Ala Gln Pro Ser Phe Val Glu
195 200
<210> 65
<211> 183
<212> PRT
<213> Acinetobacter baumannii
<400> 65
Met Gly Val Ser Ser Phe Thr Phe Ala Gly Asn Trp Gln Val Lys Phe
1 5 10 15
Gly Gly Ser Val Ile Ala Pro Ser Glu Asp Thr Thr Thr Ala Leu Gly
20 25 30
Val Val Lys Ala Asp His Glu Tyr Ala Phe Thr Pro Ser Val Glu Tyr
35 40 45
Phe Phe Gly Gln Ser Pro Phe Ser Ala Glu Leu Leu Leu Ala Thr Pro
50 55 60
Val Asn His Asp Val Leu Leu Asp Gly Gln Lys Val Ala Arg Ile Lys
65 70 75 80
Gln Leu Pro Pro Thr Ile Thr Ala Lys Tyr His Phe Lys Asn Ser Thr
85 90 95
Arg Phe Thr Pro Tyr Ile Gly Ile Gly Ala Thr Ala Phe Ile Pro Trp
100 105 110
Asp Glu Gln Gly Val Ala Asp Lys Val Lys Glu Asp Phe Gly Val Ala
115 120 125
Gly Gln Ile Gly Phe Asn Phe Gln Pro Ala Asp Ala Lys Asn Trp Gly
130 135 140
Val Phe Val Asp Val Arg Tyr Ala Asp Ile Ser Pro Glu Val Thr Leu
145 150 155 160
Thr Asn Gly Ala Lys Phe Asp Leu Asp Ile Asn Pro Phe Val Tyr Thr
165 170 175
Leu Gly Tyr Ser Tyr Lys Phe
180
<210> 66
<211> 231
<212> PRT
<213> Acinetobacter baumannii
<400> 66
Met Met Lys Ile Leu Lys Leu Ser Phe Leu Ala Leu Gly Met Gly Leu
1 5 10 15
Ser Gly Phe Ala Gln Ala Asp Phe Ile Gly Val Lys Gly Asp Val Gly
20 25 30
Tyr Trp Phe Tyr Asp Gly Lys Ala Asn Met Ser Ser Gln Ser Pro Glu
35 40 45
Asp Gln Asp Leu Asp Arg Lys Gly Ser Ala Gln Leu Ser Leu Ala Phe
50 55 60
Glu His Pro Ile Pro Phe Ile Pro Asn Ala Lys Ile Arg Tyr Val Asn
65 70 75 80
Leu Asp Thr Gln Thr Lys Ser Glu Thr Leu Gly Gln Ala Asn Tyr Asn
85 90 95
Val Asp Leu Asp His Ser Asp Phe Ile Leu Tyr Tyr Glu Leu Leu Asp
100 105 110
Asn Ile Val Ser Val Asp Ala Gly Leu Gly Ala Thr Val Leu Asn Gly
115 120 125
Asp Ile Thr Ala Tyr Thr Gly Lys Arg Val Asp Ile Asp Lys Thr Tyr
130 135 140
Pro Ile Ala Tyr Leu Ser Gly Glu Val Lys Leu Pro Phe Thr Gly Leu
145 150 155 160
Ser Ala Lys Gly Glu Ala Thr Tyr Thr Asn Phe Asp Asp Ala Lys Ile
165 170 175
Thr Asp Ala Leu Val Glu Ala Lys Tyr Lys Phe Ala Asp Asn Leu Leu
180 185 190
Ile Asp Leu Gly Leu Thr Ala Gly Tyr Arg Ile Leu Asn Ile Asp Leu
195 200 205
Asp Asp Tyr Asp Asn Asn Asp Leu Lys Phe Glu Phe Lys Gly Pro Tyr
210 215 220
Val Gly Leu Glu Ala His Phe
225 230
<210> 67
<211> 142
<212> PRT
<213> Acinetobacter baumannii
<400> 67
Met Asp Asp Leu Lys Glu Asn Val Lys Glu Lys Gln Thr Ala Gly Lys
1 5 10 15
Glu Ala Val Ala Asp Lys Val Asp Glu Leu Lys Thr Lys Ala Ala Asp
20 25 30
Ala Lys Val Gln Gly Glu Lys Ala Leu Glu Asp Leu Lys Glu Asn Val
35 40 45
Lys Glu Lys Gln Ala Ala Ala Lys Glu Ala Val Glu Asp Lys Ala Ser
50 55 60
Asp Leu Lys Gly Lys Leu Asp Asp Ala Gln His Ser Leu Gln Asp Lys
65 70 75 80
Phe Asp His Leu Arg Thr Glu Ala Ala His Lys Leu Asp Asp Ala Lys
85 90 95
Ala Lys Ala Ala Glu Leu Lys Glu Glu Ala Ala Thr Lys Phe Asp Glu
100 105 110
Leu Lys Thr Gln Ala Thr Ala Lys Phe Asp Glu Leu Lys Lys Thr Ala
115 120 125
Thr Glu Lys Leu Asn Lys Leu Lys Asn His Asp Ser Ala Glu
130 135 140
<210> 68
<211> 344
<212> PRT
<213> Acinetobacter baumannii
<400> 68
Met Lys Ala Gln Val His Ala Gly Gly Arg Gly Lys Ala Gly Gly Val
1 5 10 15
Lys Val Ala Lys Ser Lys Glu Asp Val Ile Glu Phe Ala Asn Asn Ile
20 25 30
Ile Gly Thr Arg Leu Val Thr Tyr Gln Thr Asp Ala Asn Gly Gln Pro
35 40 45
Val Asn Ser Ile Ile Val Ala Glu Asp Val Tyr Pro Val Glu Arg Glu
50 55 60
Leu Tyr Leu Gly Ala Val Val Asp Arg Ser Ser Arg Arg Ile Thr Phe
65 70 75 80
Met Ala Ser Thr Glu Gly Gly Val Glu Ile Glu Lys Val Ala Glu Glu
85 90 95
Thr Pro Glu Lys Ile Ile Lys Val Glu Val Asp Pro Leu Val Gly Leu
100 105 110
Gln Pro Phe Gln Ala Arg Glu Val Ala Phe Ala Leu Gly Leu Lys Asp
115 120 125
Lys Gln Ile Gly Gln Phe Val Lys Ile Met Thr Ala Ala Tyr Gln Ala
130 135 140
Phe Val Glu Asn Asp Phe Ala Leu Phe Glu Ile Asn Pro Leu Ser Val
145 150 155 160
Arg Glu Asn Gly Glu Ile Leu Cys Val Asp Ala Lys Val Gly Ile Asp
165 170 175
Ser Asn Ala Leu Tyr Arg Leu Pro Lys Val Ala Ala Leu Arg Asp Lys
180 185 190
Ser Gln Glu Asn Glu Arg Glu Leu Lys Ala Ser Glu Phe Asp Leu Asn
195 200 205
Tyr Val Ala Leu Glu Gly Asn Ile Gly Cys Met Val Asn Gly Ala Gly
210 215 220
Leu Ala Met Ala Thr Met Asp Ile Ile Lys Leu Tyr Gly Gly Gln Pro
225 230 235 240
Ala Asn Phe Leu Asp Val Gly Gly Gly Ala Thr Lys Glu Arg Val Ile
245 250 255
Glu Ala Phe Lys Ile Ile Leu Ala Asp Thr Ser Val Gln Gly Val Leu
260 265 270
Ile Asn Ile Phe Gly Gly Ile Val Arg Cys Asp Met Ile Ala Glu Ala
275 280 285
Ile Ile Ala Ala Val Gln Glu Val Asn Val Thr Val Pro Val Val Val
290 295 300
Arg Leu Glu Gly Asn Asn Ala Glu Leu Gly Ala Lys Leu Leu Asp Glu
305 310 315 320
Ser Gly Leu Lys Leu Ile Ser Ala Asn Gly Leu Ser Asp Ala Ala Glu
325 330 335
Lys Val Val Ala Ala Val Lys Ala
340
<210> 69
<211> 415
<212> PRT
<213> Acinetobacter baumannii
<400> 69
Met Met Ser Ala Lys Leu Trp Ala Pro Ala Leu Thr Ala Cys Ala Leu
1 5 10 15
Ala Thr Ser Ile Ala Leu Val Gly Cys Ser Lys Gly Ser Asp Glu Lys
20 25 30
Gln Gln Ala Ala Ala Ala Gln Lys Met Pro Pro Ala Glu Val Gly Val
35 40 45
Ile Val Ala Gln Pro His Ser Val Glu Gln Ser Val Glu Leu Ser Gly
50 55 60
Arg Thr Ser Ala Tyr Gln Ile Ser Glu Val Arg Pro Gln Thr Ser Gly
65 70 75 80
Val Ile Leu Lys Arg Leu Phe Ala Glu Gly Ser Tyr Val Arg Glu Gly
85 90 95
Gln Ala Leu Tyr Glu Leu Asp Ser Arg Thr Asn Arg Ala Thr Leu Glu
100 105 110
Asn Ala Lys Ala Thr Leu Leu Gln Gln Gln Ala Asn Leu Ala Ser Leu
115 120 125
Arg Thr Lys Leu Asn Arg Tyr Lys Gln Leu Val Ser Ser Asn Ala Val
130 135 140
Ser Lys Gln Glu Tyr Asp Asp Leu Leu Gly Gln Val Asn Val Ala Glu
145 150 155 160
Ala Gln Val Ser Ala Ala Lys Ala Gln Val Thr Asn Ala Asn Val Asp
165 170 175
Leu Gly Tyr Ser Thr Ile Arg Ser Pro Ile Ser Gly Gln Ser Gly Arg
180 185 190
Ser Ser Val Thr Ala Gly Ala Leu Val Thr Ala Asn Gln Thr Asp Pro
195 200 205
Leu Val Thr Ile Gln Gln Leu Asp Pro Ile Tyr Val Asp Ile Asn Gln
210 215 220
Ser Ser Ala Glu Leu Leu Arg Leu Arg Gln Gln Leu Ser Lys Gly Ser
225 230 235 240
Leu Asn Asn Ser Asn Asn Thr Lys Val Lys Leu Lys Leu Glu Asp Gly
245 250 255
Ser Thr Tyr Pro Ile Glu Gly Gln Leu Ala Phe Ser Asp Ala Ser Ala
260 265 270
Asn Gln Asp Thr Gly Thr Ile Thr Leu Arg Ala Val Phe Ser Asn Pro
275 280 285
Asn His Leu Leu Leu Pro Gly Met Tyr Thr Thr Ala Gln Ile Val Gln
290 295 300
Gly Val Val Pro Asn Ala Tyr Leu Ile Pro Gln Ala Ala Ile Thr Arg
305 310 315 320
Leu Pro Thr Gly Gln Ala Val Ala Met Leu Val Asn Ala Lys Gly Ala
325 330 335
Val Glu Ser Arg Pro Val Glu Thr Ser Gly Val Gln Gly Gln Asn Trp
340 345 350
Ile Val Thr Asn Gly Leu Lys Ala Gly Asp Lys Val Ile Val Asp Gly
355 360 365
Val Ala Lys Val Lys Glu Gly Gln Glu Val Ser Ala Lys Pro Tyr Gln
370 375 380
Ala Gln Pro Ala Asn Pro Gln Gly Ala Ala Pro Asn Ala Thr Lys Pro
385 390 395 400
Ala Gln Ser Gly Lys Pro Gln Ala Glu Gln Lys Ala Ser Asn Ala
405 410 415
<210> 70
<211> 656
<212> PRT
<213> Acinetobacter baumannii
<400> 70
Met Asp Ser Ser Ser Ser Ala Thr Arg Ser Glu Ile Ala Leu Gln Asp
1 5 10 15
Thr Pro Gln Ser Val Ser Val Val Thr Gln Lys Val Ile Glu Asp Ile
20 25 30
Gly Ala Thr Arg Leu Val Glu Ala Leu Asp Leu Ala Gly Gly Val Thr
35 40 45
Arg Ala Asn Asn Phe Gly Gly Gln Gly Leu Thr Gly Phe Asn Val Arg
50 55 60
Gly Phe Thr Ser Gly Glu Phe Tyr Arg Asn Gly Phe Pro Ile Asn Arg
65 70 75 80
Gly Tyr Pro Asn Ala Pro Asp Ser Asn Thr Ile Glu Arg Val Asp Val
85 90 95
Leu Arg Gly Pro Ser Ser Ser Leu Tyr Gly Arg Gly Asp Pro Gly Gly
100 105 110
Thr Phe Asn Leu Ile Ser Lys Thr Pro Asn Ser Glu Gln Gln Thr Thr
115 120 125
Leu Gly Ala Gln Leu Asn Ser Glu Gly Leu Tyr Arg Thr Thr Val Asp
130 135 140
Thr Thr Gly Thr Ile Pro Asn Ala Glu Asn Ile Gly Tyr Arg Leu Asn
145 150 155 160
Val Ile Ala Glu Gly Gly Asp Ser Tyr Arg Asp His Val Glu Ser Lys
165 170 175
Arg Tyr Gly Ile Ala Pro Val Ile Gln Trp Gln Ala Thr Asp Ala Thr
180 185 190
Lys Val Thr Phe Glu Ala Asp Ile Leu Arg Asn Gln His Pro Leu Asp
195 200 205
Arg Gly His Thr Arg Tyr Pro Thr Gln Lys Ser Phe Asn Ser Ser Pro
210 215 220
Glu Thr Tyr Leu Trp Glu Thr Gly Lys Tyr Tyr Asn Arg Leu Tyr Asn
225 230 235 240
Asp Asn Asn Met Thr Gln Leu Arg Val Glu His Asp Leu Gly Asn Asp
245 250 255
Trp Lys Leu Asn Ala Gly Val Gln Tyr Leu Asn Gly Lys Leu His Gly
260 265 270
Tyr Ala Val Glu Ala Asn Gly Ile Gln Asn Asp Gly Glu Thr Leu Gly
275 280 285
Arg Asn Tyr Asn Tyr Arg Glu Leu Lys Trp Gln Asp Thr Asp Ala Gln
290 295 300
Ile Asn Leu Thr Gly Asn Phe Gln Leu Leu Gly Leu Ala His Thr Leu
305 310 315 320
Val Thr Gly Leu Glu Tyr Glu Asn Tyr Asp Tyr Lys Ser Tyr Ile Ile
325 330 335
Arg Ser Ser Glu Asp Ile Gly Ser Tyr Ser Ile Asn Ile Tyr Asn Pro
340 345 350
Val Leu Gly Gln Pro Leu Pro Glu Leu Asn Thr Val Thr Thr His Asp
355 360 365
Arg Glu Asn Leu Lys Thr Thr Ala Leu Phe Val Gln Asp Gln Leu Glu
370 375 380
Leu Asn Glu Arg Leu Ser Ala Leu Leu Gly Leu Arg Phe Glu His Tyr
385 390 395 400
Glu His Asp Tyr Gln Asp Leu Arg Pro Gly Lys Pro Asn Trp Asn Thr
405 410 415
Ser His Asp Ala Phe Ile Pro Arg Leu Gly Leu Val Tyr Lys Ala Ser
420 425 430
Asp Asp Leu Ser Leu Tyr Gly Asn Ala Ala Lys Ser Phe Lys Pro Asn
435 440 445
Thr Gly Ala Ser His Ser Gly Glu Gly Phe Asp Pro Glu Glu Gly Met
450 455 460
Ala Tyr Glu Leu Gly Phe Lys Trp Leu Ala Leu Asn Asn Met Leu Ser
465 470 475 480
Val Asp Ser Ala Ile Phe Tyr Ala Asn Lys Glu Asn Val Leu Thr Asn
485 490 495
Asp Pro Leu Phe Pro Asn Tyr Lys Val Ala Ala Gly Glu Val Arg Ser
500 505 510
Arg Gly Ile Glu Leu Asn Ile Ala Gly Gln Ile Thr Pro Ala Trp Lys
515 520 525
Ile Ile Gly Gly Tyr Ala Tyr Thr Asp Ala Glu Val Thr Lys Asp Asn
530 535 540
Thr Leu Gln Lys Gly Thr Ala Leu Ala Asn Ile Pro Lys Asn Ser Phe
545 550 555 560
Asn Leu Leu Asn Ile Tyr Glu Phe Gln Asp Gly Pro Leu Gln Gly Leu
565 570 575
Gly Leu Gly Ile Asn Gln Lys Tyr Ile Asp Lys Arg Ala Gly Gln Thr
580 585 590
Ala Asn Ser Thr Tyr Ile Met Lys Gly Tyr Ala Val Thr Asp Leu Val
595 600 605
Ser Tyr Tyr Gln Ala Thr Pro Lys Leu Arg Leu Asn Leu Asp Val Lys
610 615 620
Asn Ile Phe Asp Lys Val Tyr Asp Glu Ser Ala Phe Asn Leu Tyr Ala
625 630 635 640
Tyr Pro Gly Glu Ser Arg Thr Val Gln Leu Gly Met Ser Tyr Thr Phe
645 650 655
<210> 71
<211> 177
<212> PRT
<213> Acinetobacter baumannii
<400> 71
Met Asp Arg Met Arg Gly Glu Asp Asp Tyr Lys Ser Thr Tyr Phe Glu
1 5 10 15
Leu Ser Pro Arg Leu Ser Leu Gly Glu Val Ser Gly Lys Lys Leu Thr
20 25 30
Tyr Gly Pro Ile Lys Asp Val Leu Ile Ser Thr Thr Trp Glu Ser Asn
35 40 45
Thr Gln Asn Gly Asn Asn Phe Asp Asn Phe Leu Tyr Gly Phe Ala Val
50 55 60
Asp Leu Asp Ile Pro Tyr Phe Gln Tyr Ala Asn Leu Asn Phe Tyr Arg
65 70 75 80
Ala Asn Asn Glu Lys Thr Asp Asp Asp Tyr Gln Met Thr Phe Val Tyr
85 90 95
Gly Ile Pro Phe Lys Ile Ala Ser Glu Asp Phe Leu Val Asp Gly Phe
100 105 110
Leu Asp Trp Ser Thr Ala Glu Asp Asp His Ala Ser Glu Leu Asn Trp
115 120 125
Thr Thr Gln Trp Lys Trp Asn Val Gly Lys His Ile Ser Pro Asp Thr
130 135 140
Arg Leu Tyr Leu Gly Ile Glu His Ser Val Trp Asn Asn Lys Phe Gly
145 150 155 160
Ile Lys Gly Ala Asp Glu Asn Asn Val Ser Ala Leu Val Lys Tyr His
165 170 175
Phe
<210> 72
<211> 581
<212> PRT
<213> Acinetobacter baumannii
<400> 72
Met Tyr Ala Asn Lys Asn Gln Lys Ser Glu Val Thr Tyr Ala Gly Tyr
1 5 10 15
Phe Leu Ser Glu Asn Gly Asn Asn Asn Leu Lys Glu Glu Leu Lys Ala
20 25 30
Asp Ile Ser Ala Leu Phe Ile Pro Thr Gln Asp Asn Gln Ser Ile Arg
35 40 45
Cys Lys Phe Pro Ala Arg Ser Gln Trp Leu Ile Gln Gln Leu Gly Ile
50 55 60
Gln Glu Asn Glu Leu Pro Gln Val Lys Cys Ser Glu Phe Glu Asn Trp
65 70 75 80
Ile Gly Gln Ile Lys Pro Tyr Lys Ala Thr Leu Ile Tyr Ala Thr Asp
85 90 95
Phe Met Gly Asn Pro Ser Ser Met Phe Gly His Thr Leu Leu Arg Leu
100 105 110
Asp Pro Lys Asp Gln Gln Gln Leu Asn Leu Val Ser Tyr Ala Val Asn
115 120 125
Tyr Ala Ala Thr Val Ala Gly Asn Asp Asn Trp Ser Tyr Ala Trp Lys
130 135 140
Gly Leu Thr Gly Gln Tyr Pro Gly Glu Tyr Ser Leu Met Pro Tyr Tyr
145 150 155 160
Arg Lys Val Lys Glu Tyr Gly Asp Phe Glu Ser Arg Asp Leu Trp Glu
165 170 175
Tyr Glu Leu Asn Leu Ser Pro Glu Glu Thr Arg Phe Leu Val Ser His
180 185 190
Ile Trp Glu Met Gln His Val Ser Phe Pro Tyr Tyr Phe Val Ser Asp
195 200 205
Asn Cys Ala Tyr Arg Leu Leu Gly Leu Val Asp Leu Val Lys Pro Glu
210 215 220
Ser His Leu Gln Glu Lys Phe Asn Tyr Ala Ser Ile Pro Met Glu Thr
225 230 235 240
Ile Lys Ala Met Gln Gln Gln Gly Leu Thr Lys Ala Pro Val Tyr Arg
245 250 255
Pro Ala Leu Glu Thr Gln Leu Leu Ala Gln Ala His Gln His Gly Ala
260 265 270
Ser Leu Ala Lys Val Ala His Gln Leu Ala Met Lys Pro Ile Lys Glu
275 280 285
Ser Ser Glu Thr Leu Lys Ser Phe Ser Pro Ser Asp Gln Ala Lys Ile
290 295 300
Leu Glu Met Ala Tyr Asp Asp Leu Tyr Leu Gln Phe Ile Gly Arg Lys
305 310 315 320
Val Glu Glu Ser Phe Ala Gln Pro Gln Leu Arg Gln Leu Leu Ala Leu
325 330 335
Arg Ser Gln Ile Asp Leu Asp Lys Gln Arg Gln Glu Pro Lys Arg Pro
340 345 350
Ser Thr Glu Pro Thr Gln Gly His Asn Ala Arg Asn Val Ser Leu Lys
355 360 365
Leu Gly Glu Val Gln Gly Asp Lys Phe Ile Glu Ile Gly His Arg Gln
370 375 380
Ala Tyr His Asp Leu Ile Asp Pro Gln Gly Gly Tyr Arg Ala Gly Thr
385 390 395 400
Gln Leu Leu Phe Leu Asn Gly Asn Ala Gln Trp Arg Asp Asp His Leu
405 410 415
Lys Leu Glu Arg Leu Asp Leu Leu Glu Val Asn Ser Tyr Asn Pro Ile
420 425 430
Gln Pro Phe Lys Thr Pro Leu Thr Trp Gly Phe Asn Leu Gly Trp Arg
435 440 445
Gln Glu Ala Val His Asp Gly Val Tyr Ser Asp Glu Lys Gln His Gly
450 455 460
Val Ala Ser Phe Asn Ala Gln Val Gly Tyr Ser Leu Ala Asp Tyr Glu
465 470 475 480
Arg Lys His Ile Cys Tyr Gly Gln Val Gln Thr Tyr Val Gln Ala Gly
485 490 495
Ser Asn Leu Asp Lys Gly Trp Arg Val Gly Val Gly Pro Thr Leu Gly
500 505 510
Cys Met Asn Gln Trp Leu Glu Lys Phe Asn Thr Val Val Gln Val Glu
515 520 525
Leu Pro Tyr Trp Glu Asp Gln Asn Gln Trp Asn Leu Arg Leu Asn Thr
530 535 540
Gln Trp Gln Tyr Ala Ile Asn Ser Asn Asn Ala Ile Arg Phe Asn Trp
545 550 555 560
Asp Tyr Glu Lys Gln Asn His Leu Asp Trp Met Lys Ser Ser Leu Gly
565 570 575
Tyr Val Trp Phe Phe
580
<210> 73
<211> 205
<212> PRT
<213> Acinetobacter baumannii
<400> 73
Met Arg Gly Asn Asn Val Asn Leu Lys Thr Val Ser Gly Ser Ala Val
1 5 10 15
Glu Leu Ser Glu Val Ala Phe Gly Arg Glu Phe Asn Glu Ala Leu Val
20 25 30
His Gln Val Val Thr Ala Tyr Leu Ala Gly Gly Arg Gln Gly Thr Arg
35 40 45
Ala Gln Lys Ser Arg Ala Glu Val Ser Gly Gly Gly Lys Lys Pro Phe
50 55 60
Arg Gln Lys Gly Thr Gly Arg Ala Arg Ala Gly Ser Ile Arg Ser Pro
65 70 75 80
Ile Trp Val Gly Gly Gly Lys Thr Phe Ala Ala Arg Pro Gln Asp Trp
85 90 95
Ser Gln Lys Val Asn Arg Lys Met Tyr Arg Gly Ala Met Gln Cys Ile
100 105 110
Leu Ala Glu Leu Val Arg Gln Asp Arg Leu Val Leu Val Glu Glu Phe
115 120 125
Ala Val Ala Ala Pro Lys Thr Lys Glu Leu Leu Ala Lys Leu Asn Asp
130 135 140
Leu Asn Ala Ala Arg Ala Leu Ile Val Thr Asp Ala Val Asp Glu Asn
145 150 155 160
Leu Tyr Leu Ala Ala Arg Asn Leu Pro His Val Asp Val Val Asp Ala
165 170 175
Thr Ala Ile Asp Pro Val Ser Leu Ile Ala Phe Asp Lys Val Val Met
180 185 190
Ser Val Ala Ala Ala Lys Lys Ile Glu Val Glu Leu Gly
195 200 205
<210> 74
<211> 152
<212> PRT
<213> Acinetobacter baumannii
<400> 74
Met Lys Gly Ser Lys Gly Thr Leu Ser Phe Asn Leu His Ala Leu Val
1 5 10 15
Glu Leu Lys Gln Glu Glu Gly Lys Leu Gln Leu Ala Pro Ala Lys Glu
20 25 30
Ser Lys Asp Ala Trp Met Gln Ala Gly Thr Ala Arg Ala Val Leu Asn
35 40 45
Asn Leu Val Lys Gly Val Ser Glu Gly Phe Glu Arg Lys Leu Gln Leu
50 55 60
Val Gly Val Gly Tyr Lys Ala Ala Val Lys Gly Thr Val Val Asn Leu
65 70 75 80
Asn Leu Gly Tyr Ser His Pro Ile Asp Tyr Ala Leu Pro Glu Gly Val
85 90 95
Thr Ala Glu Thr Pro Thr Ala Thr Glu Ile Ile Leu Lys Ser Ala Asn
100 105 110
Lys Gln Leu Leu Gly Gln Val Ala Ala Glu Ile Arg Ala Tyr Arg Ser
115 120 125
Pro Glu Pro Tyr Lys Gly Lys Gly Val Arg Tyr Ser Asp Glu Val Ile
130 135 140
Leu Arg Lys Glu Ala Lys Lys Lys
145 150
<210> 75
<211> 221
<212> PRT
<213> Acinetobacter baumannii
<400> 75
Met Thr Asn Leu Thr Asp Tyr Val Val Leu Asn Thr Ser Val Ala Ser
1 5 10 15
Gly Glu Gln Asp Val Asn Ala Phe Gln Ser Phe Asn Tyr Leu Ala Ala
20 25 30
Tyr Asn Ala Ser Asn Lys Ala Lys Val Ala Ala Val Ala Thr Thr Tyr
35 40 45
Leu Glu Pro Met Gly Ile Tyr Ala Asn Lys Val Lys Thr Val Asp Glu
50 55 60
Phe Pro Gln Gly Ala Thr Ile Ala Ile Pro Asn Asp Thr Ala Asn Glu
65 70 75 80
Ala Arg Ala Leu Thr Leu Leu Gln Ser Ala Lys Leu Ile Lys Leu Lys
85 90 95
Pro Asp Phe Asp Pro Val Lys Gly Thr Thr Asn Asp Val Val Glu Asn
100 105 110
Pro Lys Asn Leu Gln Leu Lys Pro Ile Gln Met Thr Thr Ala Val Arg
115 120 125
Val Lys Asn Asp Val Asp Ala Ile Val Leu Gly Asn Thr Leu Ala Leu
130 135 140
Glu Gly Gly Leu Asn Val Met Lys Asp Ala Ile Phe Arg Glu Pro Ile
145 150 155 160
Asp Gln Ser Thr Lys Leu Tyr Val Asn Leu Leu Gly Val Ala Glu Ala
165 170 175
Asn Lys Asn Asp Pro Ile Tyr Thr Lys Leu Gly Glu Leu Tyr His Leu
180 185 190
Pro Lys Val Gln Lys Phe Val Asn Glu Lys Phe Gly Gly Thr Lys Val
195 200 205
Glu Val Asn Lys Pro Val Ser Glu Phe Ala Asp Ile Lys
210 215 220
<210> 76
<211> 99
<212> PRT
<213> Acinetobacter baumannii
<400> 76
Met Ala Thr Ala Val Arg Val Lys Asp Glu Val Asp Ala Ile Val Leu
1 5 10 15
Gly Asn Thr Leu Ala Met Glu Gly Gly Leu Asn Val Leu Lys Asp Ser
20 25 30
Ile Tyr Tyr Glu Pro Val Asp Gln Ser Thr Lys Leu Asn Val Asn Ile
35 40 45
Leu Ala Thr Ala Glu Ser Arg Lys Asp Asp Pro Val Leu Gln Lys Val
50 55 60
Gly Gln Leu Tyr His Thr Glu Ala Val Lys Lys Tyr Val Glu Gln His
65 70 75 80
Phe Gly Gly Thr Lys Val Asp Val Asn Gln Pro Ile Ser Tyr Leu Thr
85 90 95
Gln Ala Lys
<210> 77
<211> 169
<212> PRT
<213> Acinetobacter baumannii
<400> 77
Met Val Asn Glu Thr Met Lys His Gln Phe Lys Phe Asn Pro Leu Ala
1 5 10 15
Thr Ala Ile Phe Thr Leu Leu Cys Ser Gly Ser Ile Gln Ser Ser Tyr
20 25 30
Ala Glu Ser Ala Gly Val Val Ser Asn Ile Asp Asn Asn Gln Leu Lys
35 40 45
Ala Ser Ile Lys Glu Ala Tyr Pro Gly Gln Glu Phe Phe Gln Gln Tyr
50 55 60
Tyr Val Asp Lys Ser Ala Pro Glu Ala Gln Leu Arg Asn Asn Lys Tyr
65 70 75 80
Leu Ser Ser Ala Phe Cys Gln Gly Thr Trp Ile Thr Pro Ile Asn Pro
85 90 95
Glu Thr Lys Ala Leu Asp Ala Asp Lys Ala Thr Ser Val Val Thr Ala
100 105 110
Asp Tyr Gly His Tyr Asn Pro Ala Gly Asp Ser Val Leu Glu Gly Asn
115 120 125
Val Val Ile Asp Gln Glu Gly Arg Thr Val Arg Ala Asp Lys Val Thr
130 135 140
Ile Asp Lys Thr Gln Thr Phe Ala His Ala Gln Gly Arg Val Gln Leu
145 150 155 160
Ala Gln Gly Gly Leu Leu Ser Thr Lys
165
<210> 78
<211> 236
<212> PRT
<213> Acinetobacter baumannii
<400> 78
Met Ser Arg Gly Thr Arg Thr Phe Glu Ile Tyr Arg Tyr Asp Pro Asp
1 5 10 15
Lys Asp Lys Ala Pro Tyr Met Gln Thr Phe Lys Leu Glu Leu Thr Asp
20 25 30
Lys His Arg Met Leu Leu Asp Ala Leu Leu Ala Leu Lys Val Gln Asp
35 40 45
Glu Thr Leu Thr Phe Arg Arg Ser Cys Arg Glu Gly Ile Cys Gly Ser
50 55 60
Asp Gly Val Asn Ile Asn Gly Lys Asn Gly Leu Ala Cys Leu Trp Asn
65 70 75 80
Leu Asn Asp Leu Pro Glu Lys Ile Val Ile Arg Pro Leu Pro Gly Leu
85 90 95
Pro Val Ile Lys Asp Leu Val Val Asp Met Asn Gln Phe Tyr Asp Gln
100 105 110
Tyr Asp Lys Ile Gln Pro Phe Leu Ile Asn Asn Gln Pro Ala Pro Pro
115 120 125
Lys Glu Arg Leu Gln Ser Pro Glu Glu Arg Glu His Leu Asn Gly Leu
130 135 140
Tyr Glu Cys Ile Leu Cys Ala Cys Cys Ser Thr Ser Cys Pro Ser Phe
145 150 155 160
Trp Trp Asn Pro Asp Lys Phe Leu Gly Pro Ser Ala Leu Leu Asn Ala
165 170 175
Tyr Arg Phe Ile Ile Asp Ser Arg Asp Thr Ala Thr Gln Asp Arg Leu
180 185 190
Ser Arg Leu Asp Asp Pro Phe Ser Leu Phe Arg Cys Lys Gly Ile Met
195 200 205
Asn Cys Val Ser Val Cys Pro Lys Gly Leu Asn Pro Thr Lys Ala Ile
210 215 220
Gly His Ile Arg Asn Met Leu Phe Asp Gln Ala Gly
225 230 235
<210> 79
<211> 300
<212> PRT
<213> Acinetobacter baumannii
<400> 79
Met Leu Gly Lys Asp Gln Pro Val Ile Leu Gln Leu Leu Glu Val Pro
1 5 10 15
Val Glu Lys Ala Gln Gln Ala Leu Lys Gly Val Met Met Glu Leu Asp
20 25 30
Asp Cys Ala Phe Pro Leu Leu Ala Gly Met Ile Gly Thr Asp Asp Pro
35 40 45
Lys Val Ala Phe Lys Asp Ala Asp Tyr Ala Leu Leu Val Gly Ser Arg
50 55 60
Pro Arg Gly Pro Gly Met Glu Arg Ala Asp Leu Leu Lys Val Asn Gly
65 70 75 80
Glu Ile Phe Ile Gly Gln Gly Gln Ala Leu Asn Glu Val Ala Ser Arg
85 90 95
Asp Val Lys Val Leu Val Val Gly Asn Pro Ala Asn Thr Asn Ala Tyr
100 105 110
Ile Ala Met Lys Ser Ala Pro Asp Leu Pro Ala Lys Asn Phe Thr Ala
115 120 125
Met Leu Arg Leu Asp His Asn Arg Ala Leu Thr Gln Val Ala Gln Lys
130 135 140
Ala Gly Val Ala Val Ala Asp Ile Glu Lys Leu Thr Val Trp Gly Asn
145 150 155 160
His Ser Pro Thr Met Tyr Ala Asp Tyr Arg Phe Ala Thr Ala Asn Gly
165 170 175
Glu Ser Leu Lys Asp Lys Ile Asn Asp Pro Ala Trp Asn Lys Asp Val
180 185 190
Phe Leu Pro Thr Val Gly Lys Arg Gly Ala Ala Ile Ile Glu Ala Arg
195 200 205
Gly Leu Ser Ser Ala Ala Ser Ala Ala Asn Ala Ala Ile Asp His Met
210 215 220
Arg Asp Trp Ala Leu Gly Thr Asn Gly Lys Trp Val Thr Met Gly Val
225 230 235 240
Pro Ser Asp Gly Ser Tyr Gly Ile Pro Glu Gly Val Met Phe Gly Phe
245 250 255
Pro Val Thr Thr Glu Asn Gly Glu Tyr Lys Ile Val Gln Gly Leu Glu
260 265 270
Ile Asp Glu Phe Ser Arg Glu Arg Ile Asn Phe Thr Leu Asn Glu Leu
275 280 285
Glu Glu Glu Arg Ala Ala Ile Ala Asp Met Val Lys
290 295 300
<210> 80
<211> 373
<212> PRT
<213> Acinetobacter baumannii
<400> 80
Met Gly Glu Pro Val Ser Arg Asp Glu Val Ile Cys Asp Ile Glu Thr
1 5 10 15
Asp Lys Val Val Leu Glu Val Val Ala Pro Ala Asp Gly Ser Leu Val
20 25 30
Ala Ile Ile Lys Gly Glu Gly Asp Thr Val Leu Ser Asp Glu Val Ile
35 40 45
Ala Gln Phe Glu Ala Gly Ala Gly Ala Ala Ala Ala Ala Pro Ala Ala
50 55 60
Val Glu Gln Ala Val Ala Gln Thr Gln Ala Gly Ala Ala Pro Val Val
65 70 75 80
Glu Arg Asn Glu Thr Val Ser Asp Gln Ala Pro Ala Val Arg Lys Ala
85 90 95
Leu Thr Glu Ser Gly Ile Ala Ala Ser Asp Val Gln Gly Thr Gly Arg
100 105 110
Gly Gly Arg Ile Thr Lys Glu Asp Val Ala Asn His Gln Ala Lys Pro
115 120 125
Ala Ala Asn Val Thr Pro Leu Ser Val Ala Val Gly Glu Arg Ile Glu
130 135 140
Lys Arg Val Pro Met Thr Arg Leu Arg Lys Arg Val Ala Glu Arg Leu
145 150 155 160
Leu Ala Ala Thr Gln Glu Thr Ala Met Leu Thr Thr Phe Asn Glu Val
165 170 175
Asn Met Lys Pro Ile Met Glu Leu Arg Lys Gln Tyr Lys Asp Ala Phe
180 185 190
Glu Lys Arg His Gly Ala Arg Leu Gly Phe Met Ser Phe Phe Val Lys
195 200 205
Ala Ala Thr Glu Ala Leu Lys Arg Tyr Pro Ala Val Asn Ala Ser Ile
210 215 220
Asp Gly Asp Asp Ile Val Tyr His Gly Tyr Tyr Asp Ile Gly Val Ala
225 230 235 240
Val Ser Ser Asp Arg Gly Leu Val Val Pro Val Leu Arg Asp Thr Asp
245 250 255
Arg Met Ser Tyr Ala Glu Val Glu Ala Gly Ile Ala Ala Tyr Ala Ala
260 265 270
Lys Ala Arg Asp Gly Lys Leu Ser Ile Glu Glu Met Thr Gly Gly Thr
275 280 285
Phe Thr Ile Thr Asn Gly Gly Thr Phe Gly Ser Leu Leu Ser Thr Pro
290 295 300
Ile Leu Asn Gln Pro Gln Thr Gly Ile Leu Gly Met His Lys Ile Gln
305 310 315 320
Glu Arg Pro Met Ala Val Asn Gly Gln Val Glu Ile Leu Pro Met Met
325 330 335
Tyr Leu Ala Leu Ser Tyr Asp His Arg Met Ile Asp Gly Lys Glu Ala
340 345 350
Val Gly Phe Leu Val Ala Ile Lys Glu Leu Leu Glu Glu Pro Ala Lys
355 360 365
Leu Ile Leu Asp Leu
370
<210> 81
<211> 468
<212> PRT
<213> Acinetobacter baumannii
<400> 81
Met Ser Phe Ser Met Thr Lys Leu Ser Ala Ala Leu Leu Leu Thr Ser
1 5 10 15
Ser Leu Val Gly Cys Ala Ala Val Val Lys Thr Pro Tyr Gln Ala Pro
20 25 30
Ala Val Gln Val Pro Gly Ser Phe Gln Tyr Asp Lys Ala Lys Ala Lys
35 40 45
Thr Ala Ser Val Glu Gln Tyr Ser Asp Arg Trp Trp Thr Leu Phe Gly
50 55 60
Asp Thr Gln Leu Asn Gln Leu Val Thr Asn Val Leu Glu Arg Asn Ser
65 70 75 80
Asp Leu Ala Val Ala Gly Ile Thr Leu Gln Gln Ala Arg Leu Gln Ala
85 90 95
Asp Leu Thr Ala Asn Lys Gln Gly Leu Arg Thr Ser Ser Ser Val Ser
100 105 110
Thr Gly His Ser Phe Asp Leu Asn Ser Gly Asp Asp Ser Ala Lys Gly
115 120 125
Leu Ser Met Ser Ala Gly Val Ser Tyr Glu Leu Asp Leu Phe Gly Lys
130 135 140
Leu Ala Arg Gln Thr Glu Ala Ser Lys Trp Glu Ala Leu Ala Thr Glu
145 150 155 160
Gln Asp Leu Gln Ala Thr Gly Gln Ser Leu Ile Ala Thr Thr Ala Lys
165 170 175
Leu Tyr Trp Gln Leu Gly Tyr Leu Asn Glu Arg Tyr Ala Thr Ala Gln
180 185 190
Gln Ser Leu Ala Thr Ser Gln Lys Leu Tyr Gln Leu Val Gln Thr Gln
195 200 205
Tyr Lys Ala Gly Ala Val Ser Gly Leu Asp Leu Thr Gln Ala Glu Gln
210 215 220
Ser Val Gln Ser Gln Lys Ala Ser Leu Ser Gln Ile Glu Gln Gln Leu
225 230 235 240
Val Glu Thr Arg Thr Ala Ile Ala Val Leu Leu His Glu Pro Leu Gln
245 250 255
Gln Leu Asn Ile Gln Glu Pro Gln Arg Leu Pro Arg Thr Ala Leu Pro
260 265 270
Ala Ile Gly Ala Gly Leu Pro Ala Asp Ile Leu Ser Arg Arg Pro Asp
275 280 285
Leu Gln Ala Ala Glu Leu Arg Leu Arg Lys Ala Leu Ala Thr Lys Asp
290 295 300
Ala Thr Lys Ala Ser Tyr Tyr Pro Ser Ile Ser Leu Thr Ser Ser Leu
305 310 315 320
Gly Ser Ser Ser Thr Ser Leu Thr Glu Leu Leu Arg Asn Pro Ala Leu
325 330 335
Thr Leu Gly Ala Ser Leu Ser Leu Pro Phe Leu Gln Tyr Asn Asp Met
340 345 350
Lys Lys Asp Ile Ala Ile Ser Asn Leu Asp Tyr Glu Lys Ala Ile Ile
355 360 365
Gln Tyr Arg Gln Thr Leu Tyr Gln Ala Phe Ala Asp Val Glu Asn Ala
370 375 380
Leu Ser Ser Arg Thr Glu Leu Asp Lys Gln Val Ala Leu Gln Glu Arg
385 390 395 400
Asn Val Glu Leu Ala Glu Lys Thr Glu Arg Leu Thr Glu Val Arg Tyr
405 410 415
Arg Tyr Gly Ala Val Ala Leu Lys Thr Leu Leu Asp Ala Gln Gln Thr
420 425 430
Thr Arg Thr Ala Arg Leu Ser Leu Val Glu Thr Lys Gln Ser Gln Tyr
435 440 445
Asn Ala Tyr Val Thr Leu Met Gln Ala Leu Gly Gly Ser Pro Val Lys
450 455 460
Glu Leu Pro Gln
465
<210> 82
<211> 358
<212> PRT
<213> Acinetobacter baumannii
<400> 82
Met Ala Tyr Ala Asp Thr Leu Ala Pro Val Lys Pro Ala Ser Val Asp
1 5 10 15
Ala Cys Val Ala Leu Ala Ser Asn Ala Asp Arg Leu Ala Cys Tyr Asp
20 25 30
Ala Val Phe Lys Pro Ser Ala Leu Pro Val Val Gln Ala Ala Val Val
35 40 45
Pro Glu Pro Val Lys Lys Ile Asp Lys Pro Val Val Gln Pro Glu Thr
50 55 60
Phe Lys Glu Lys Val Val Asp Lys Val Ser Asn Ile Lys Val Ile Gly
65 70 75 80
Lys Ala Pro Thr Leu Glu Pro Thr Thr Ser Leu Leu Asp Gln Arg Trp
85 90 95
Glu Leu Ser Glu Lys Ser Lys Leu Gly Val Trp Asn Ile Arg Ala Tyr
100 105 110
Gln Pro Val Tyr Leu Leu Pro Val Phe Trp Thr Ser Asp Lys Asn Glu
115 120 125
Phe Pro Ser Ser Pro Asn Pro Asn Asn Thr Val Thr Glu Ala Gln Asn
130 135 140
Leu Lys Ser Thr Glu Ser Lys Phe Gln Ile Ser Leu Lys Thr Lys Ala
145 150 155 160
Trp Glu Asn Ile Phe Gly Asn Asn Gly Asp Leu Trp Val Gly Tyr Thr
165 170 175
Gln Ser Ser Arg Trp Gln Thr Phe Asn Ala Glu Glu Ser Arg Pro Phe
180 185 190
Arg Glu Thr Asn Tyr Glu Pro Glu Ala Ser Leu Met Phe Arg Thr Asn
195 200 205
Tyr Glu Leu Leu Gly Leu Asp Gly Arg Leu Leu Gly Val Thr Leu Asn
210 215 220
His Gln Ser Asn Gly Arg Ser Asp Pro Leu Ser Arg Ser Trp Asn Arg
225 230 235 240
Val Ile Phe Asn Val Gly Leu Glu Arg Gly Asn Phe Ala Leu Met Leu
245 250 255
Arg Pro Trp Ile Arg Leu Glu Glu Asp Ser Lys Asp Asp Asn Asn Pro
260 265 270
Asp Met Glu Asp Tyr Ile Gly Arg Gly Asp Leu Thr Ala Phe Tyr Lys
275 280 285
Trp Lys Gln Asn Asp Phe Ser Leu Met Leu Arg His Ser Leu Lys Gly
290 295 300
Gly Asp Asp Ser His Gly Ala Val Gln Phe Asp Trp Ala Phe Pro Ile
305 310 315 320
Ser Gly Lys Leu Arg Gly His Phe Gln Leu Phe Asn Gly Tyr Gly Glu
325 330 335
Ser Leu Ile Asp Tyr Asn His Arg Ala Thr Tyr Ala Gly Leu Gly Val
340 345 350
Ser Leu Met Asn Trp Tyr
355
<210> 83
<211> 108
<212> PRT
<213> Acinetobacter baumannii
<400> 83
Met Glu Gly Leu Ser Val Thr Tyr Asn Gly Ser Thr Asp Thr Ala Ile
1 5 10 15
Ile Lys Gly Gln Val Gln Ser Gln Ala Asp Lys Glu Lys Ile Ile Leu
20 25 30
Ile Val Gly Asn Val Asp His Val Ala Gln Val Asp Asp Gln Met Thr
35 40 45
Val Ala Thr Pro Glu Pro Glu Ser Lys Phe Tyr Thr Val Lys Ser Gly
50 55 60
Asp Asn Leu Ser Lys Ile Ala Lys Glu Phe Tyr Gly Asp Ala Asn Gln
65 70 75 80
Tyr Gln Lys Ile Phe Glu Ala Asn Lys Pro Met Leu Lys Asp Pro Asp
85 90 95
Glu Ile Phe Pro Gly Gln Val Leu Arg Ile Pro Gln
100 105
<210> 84
<211> 291
<212> PRT
<213> Acinetobacter baumannii
<400> 84
Met Thr Ala Ile Thr Ala Ser Met Val Lys Glu Leu Arg Asp Arg Thr
1 5 10 15
Gly Leu Ala Met Met Glu Cys Lys Lys Ala Leu Thr Glu Ala Asn Gly
20 25 30
Asp Ile Glu Leu Ala Ile Asp Asn Leu Arg Lys Ser Gly Gln Ala Lys
35 40 45
Ala Ala Lys Lys Ala Gly Asn Ile Ala Ala Asp Gly Ala Ile Thr Ile
50 55 60
Val Gln Asp Gly Asn Lys Ala Ile Leu Val Glu Val Asn Cys Gln Thr
65 70 75 80
Asp Phe Val Ala Lys Asp Glu Asn Phe Ser Asn Phe Ala His Thr Val
85 90 95
Ala Ala Ala Ala Leu Ala Ala Gly Glu Thr Asp Ala Ala Lys Ile Ala
100 105 110
Glu Leu Lys Leu Ala Asp Gly Gln Ser Val Glu Glu Ala Arg Ile Ala
115 120 125
Leu Val Gln Lys Ile Gly Glu Asn Ile Gln Val Arg Arg Ala Lys Ile
130 135 140
Val Glu Gly Glu Gln Leu Ala Ile Tyr Lys His Gly Leu Lys Ile Gly
145 150 155 160
Val Val Val Ser Tyr Thr Gly Asp Ala Asp Thr Gly Lys Gly Ile Ala
165 170 175
Met His Val Ala Ala Phe Asn Pro Val Ala Val Asn Ala Glu Ala Val
180 185 190
Pro Ala Asp Leu Ile Ala Lys Glu Lys Glu Ile Ala Glu Ala Lys Ala
195 200 205
Leu Glu Ser Gly Lys Pro Ala Asn Ile Val Glu Lys Met Val Thr Gly
210 215 220
Ser Val Glu Lys Tyr Leu Asn Glu Val Ala Leu Asp Arg Gln Met Tyr
225 230 235 240
Val Ile Asp Asn Glu Lys Lys Val Ala Asp Val Leu Lys Ala Thr Gly
245 250 255
Thr Asn Val Ala Asn Phe Val Arg Phe Glu Val Gly Glu Gly Ile Glu
260 265 270
Lys Lys Ala Glu Leu Ser Phe Ala Glu Glu Val Ala Ala Ala Gln Ala
275 280 285
Ala Ala Lys
290
<210> 85
<211> 170
<212> PRT
<213> Acinetobacter baumannii
<400> 85
Met Thr Gly Cys Ala Ser Arg Lys Pro Ala Thr Thr Ala Thr Thr Gly
1 5 10 15
Thr Thr Asn Pro Ser Thr Val Asn Thr Thr Gly Leu Ser Glu Asp Ala
20 25 30
Ala Leu Asn Ala Gln Asn Leu Ala Gly Ala Ser Ser Lys Gly Val Thr
35 40 45
Glu Ala Asn Lys Ala Ala Leu Ala Lys Arg Val Val His Phe Asp Tyr
50 55 60
Asp Ser Ser Asp Leu Ser Thr Glu Asp Tyr Gln Thr Leu Gln Ala His
65 70 75 80
Ala Gln Phe Leu Met Ala Asn Ala Asn Ser Lys Val Ala Leu Thr Gly
85 90 95
His Thr Asp Glu Arg Gly Thr Arg Glu Tyr Asn Met Ala Leu Gly Glu
100 105 110
Arg Arg Ala Lys Ala Val Gln Asn Tyr Leu Ile Thr Ser Gly Val Asn
115 120 125
Pro Gln Gln Leu Glu Ala Val Ser Tyr Gly Lys Glu Ala Pro Val Asn
130 135 140
Pro Gly His Asp Glu Ser Ala Trp Lys Glu Asn Arg Arg Val Glu Ile
145 150 155 160
Asn Tyr Glu Ala Val Pro Pro Leu Leu Lys
165 170
<210> 86
<211> 144
<212> PRT
<213> Acinetobacter baumannii
<400> 86
Met Lys Lys Ile Ile Phe Leu Gly Leu Ala Leu Val Ser Leu Thr Ala
1 5 10 15
Cys Ser Ser Val Gln His Lys Asp Ser Thr Pro Pro Lys Ile Gly Ser
20 25 30
Pro Asn Pro Ala Ser Gln Tyr Cys Val Glu Gln Gly Gly Lys Leu Glu
35 40 45
Ile Arg Asn Glu Ala Asn Gly Gln Val Gly Tyr Cys His Leu Pro Asn
50 55 60
Gly Gln Val Val Glu Glu Trp Lys Leu Phe Arg Asp Asn Gln Ala Asn
65 70 75 80
Cys Val Ser Glu Glu Ala Gln Lys Leu Val Gly Leu Ser Gly Leu Thr
85 90 95
Asp Asp Gln Ile Lys Gln Lys Thr Lys Ser Glu Ile Val Arg Lys Val
100 105 110
Ala Pro Gly Gln Pro Met Thr Met Asp Tyr Arg Ser Asn Arg Val Thr
115 120 125
Val Thr Ile Asp Pro Thr Ser Lys Lys Ile Thr Gln Ala Thr Cys Gly
130 135 140
<210> 87
<211> 249
<212> PRT
<213> Acinetobacter baumannii
<400> 87
Met Lys Val Leu Arg Val Leu Val Thr Thr Thr Ala Leu Leu Ala Ala
1 5 10 15
Gly Ala Ala Met Ala Asp Glu Ala Val Val His Asp Ser Tyr Ala Phe
20 25 30
Asp Lys Asn Gln Leu Ile Pro Val Gly Ala Arg Ala Glu Val Gly Thr
35 40 45
Thr Gly Tyr Gly Gly Ala Leu Leu Trp Gln Ala Asn Pro Tyr Val Gly
50 55 60
Leu Ala Leu Gly Tyr Asn Gly Gly Asp Ile Ser Trp Thr Asp Asp Val
65 70 75 80
Ser Val Asn Gly Thr Lys Tyr Asp Leu Asp Met Asp Asn Asn Asn Val
85 90 95
Tyr Leu Asn Ala Glu Ile Arg Pro Trp Gly Ala Ser Thr Asn Pro Trp
100 105 110
Ala Gln Gly Leu Tyr Ile Ala Ala Gly Ala Ala Tyr Leu Asp Asn Asp
115 120 125
Tyr Asp Leu Ala Lys Arg Ile Gly Asn Gly Asp Thr Leu Ser Ile Asp
130 135 140
Gly Lys Asn Tyr Gln Gln Ala Val Pro Gly Gln Glu Gly Gly Val Arg
145 150 155 160
Gly Lys Met Ser Tyr Lys Asn Asp Ile Ala Pro Tyr Leu Gly Phe Gly
165 170 175
Phe Ala Pro Lys Ile Ser Lys Asn Trp Gly Val Phe Gly Glu Val Gly
180 185 190
Ala Tyr Tyr Thr Gly Asn Pro Lys Val Glu Leu Thr Gln Tyr Asn Leu
195 200 205
Ala Pro Val Thr Gly Asn Pro Thr Ser Ala Gln Asp Ala Val Asp Lys
210 215 220
Glu Ala Asn Glu Ile Arg Asn Asp Asn Lys Tyr Glu Trp Met Pro Val
225 230 235 240
Gly Lys Val Gly Val Asn Phe Tyr Trp
245
<210> 88
<211> 999
<212> PRT
<213> Acinetobacter baumannii
<400> 88
Met Arg Ala Val Glu Gly Asp Arg Leu Leu Ile Leu Lys His Gly Asp
1 5 10 15
Val Trp Lys Arg Met Ala Val Gly Phe Lys Met Asp Leu Asn His Trp
20 25 30
Asp Pro Arg Ile Glu Ala Gln Arg Ser Trp Phe Ile Ser Arg Gln Pro
35 40 45
Tyr Leu Asp Arg Leu Ser Ala Arg Ala Ser Arg Tyr Leu Tyr His Thr
50 55 60
Val Lys Glu Ala Glu Arg Arg Gly Leu Pro Thr Glu Leu Ala Leu Leu
65 70 75 80
Pro Val Ile Glu Ser Ser Tyr Asp Pro Ala Ala Thr Ser Ser Ala Ala
85 90 95
Ala Ala Gly Leu Trp Gln Phe Ile Pro Ser Thr Gly Arg Ile Tyr Gly
100 105 110
Leu Gln Gln Thr Gly Met Tyr Asp Gly Arg Arg Asp Val Val Glu Ser
115 120 125
Thr Arg Ala Ala Tyr Glu Phe Leu Gly Ser Leu Tyr Asn Gln Phe Gly
130 135 140
Ser Trp Glu Leu Ala Leu Ala Ala Tyr Asn Ala Gly Pro Gly Arg Ile
145 150 155 160
Gln Gln Ala Ile Asn Arg Asn Gln Ala Ala Gly Leu Pro Thr Asp Tyr
165 170 175
Trp Ser Leu Lys Leu Pro Gln Glu Thr Met Asn Tyr Val Pro Arg Phe
180 185 190
Leu Ala Val Ala Gln Ile Ile Lys Asn Pro Arg Ala Tyr Gly Val Ser
195 200 205
Leu Pro Pro Ile Ala Asn Arg Pro His Phe Arg Glu Val Thr Leu Ser
210 215 220
Ala Pro Leu Ser Leu Asn Glu Ile Ala Ser Val Thr Gly Leu Ser Arg
225 230 235 240
Ala Glu Leu Tyr Ala Leu Asn Pro Gly Tyr Arg Gly Glu Thr Val Asp
245 250 255
Pro Ala Ser Pro Met Arg Ile Leu Ile Pro Ala Asp Ile Ser Pro Ser
260 265 270
Val Asp Asn Lys Leu Lys Gly Met Lys Ala Gly Gly Ser Ser Gly Trp
275 280 285
Trp Ala Ser Val Thr Ser Pro Ser Lys Pro Thr Thr Thr Thr Ser Thr
290 295 300
Ser Val Thr Val Arg Thr Thr Pro Ser Thr Pro Ala Gln Pro Val Arg
305 310 315 320
Pro Ser Thr Pro Ala Lys Thr Ser Ser Ser Ser Val Thr Val Lys Thr
325 330 335
Ala Thr Pro Arg Gly Ser Asp Ala Leu Ala Ala Phe Ala Ala Ser Ala
340 345 350
Asp Val Pro Ser Ala Pro Arg Ile Pro Val Ala Val Thr Pro Ala Ala
355 360 365
Asn Ile Lys Pro Val Arg Thr Glu Pro Pro Ile Ser Ala Thr Glu Arg
370 375 380
Glu Lys Ile Leu Ala Ala Val Arg Ala Glu Gly Glu Lys Glu Thr Val
385 390 395 400
Asp Gln Ala Leu Glu Pro Gln Ala Thr Gln Ala Glu Lys Asp Gln Val
405 410 415
Val Ala Glu Leu Lys Ala Leu Ala Pro Gln Gly Thr Glu Ile Val Asp
420 425 430
Pro Tyr Asp Gly Lys Ile Lys Leu Thr Ala Ile Gln Thr Ser Gln Ser
435 440 445
Val Ala Glu Gln Gln Gly Lys Glu Val Ser Lys Gly Phe Ala Tyr Pro
450 455 460
Lys Thr Leu Ala Glu Asp Ala Thr Leu Ala Asn Ser Glu Asp Ala Gln
465 470 475 480
Arg Asn Lys Asp Lys Pro Tyr Ile Lys Thr Asp Thr Asp Val Val Val
485 490 495
Val Gln Pro Lys Gly Lys Arg Ser Thr Tyr Thr Val Gln Pro Gly Asp
500 505 510
Thr Leu Ala Val Ile Ala Met Lys Asn Gly Val Asn Trp Arg Asp Val
515 520 525
Ala Lys Trp Asn Gln Ile Asp Pro Glu Lys Thr Leu Phe Val Gly Thr
530 535 540
Ser Leu Tyr Leu Tyr Asp Ala Lys Pro Gln Glu Ala Glu Thr Thr Ala
545 550 555 560
Lys Ser Ala Ala Lys Pro Asp Val Tyr Val Val Gln Ala Asn Asp Ser
565 570 575
Leu Thr Gly Val Ala Asn Gln Phe Asn Leu Ser Val Lys Gln Leu Ala
580 585 590
Glu Tyr Asn Asp Leu Ser Val Thr Asp Gly Leu Phe Val Gly Gln Lys
595 600 605
Leu Gln Leu Lys Glu Pro Lys Gly Asn Arg Ala Ala Lys Val Glu Pro
610 615 620
Lys Ala Ile Gln Ala Ser Thr Arg Arg Ile Ala Thr Lys Ser Tyr Thr
625 630 635 640
Val Lys Arg Gly Glu Tyr Leu Lys Leu Ile Ala Asp Arg Tyr Ala Leu
645 650 655
Ser Asn Gln Glu Leu Ala Asp Leu Thr Pro Gly Leu Thr Ala Gly Ser
660 665 670
Asn Leu Ile Val Gly Gln Lys Ile Asn Val Pro Ala Lys Glu Ile Thr
675 680 685
Val Asp Glu Val Asp Asp Ser Lys Ala Ser Gly Lys Tyr Glu Lys Leu
690 695 700
Ala Ala Gly Pro Ser Tyr Lys Thr Glu Ser Tyr Lys Val Gln Arg Gly
705 710 715 720
Asp Thr Leu Ser Ser Ile Ala Thr Lys Ser Lys Ile Ser Leu Ala Glu
725 730 735
Leu Ala Glu Leu Asn Asn Leu Lys Ala Asn Ser His Val Gln Leu Gly
740 745 750
Gln Thr Leu Lys Val Pro Ala Gly Ala Ser Val Pro Asp Gln Tyr Val
755 760 765
Val Gln Ser Gly Asp Ser Leu Asn Ala Ile Ala Ala Lys Tyr Asn Leu
770 775 780
Gln Thr Ser Tyr Leu Ala Asp Leu Asn Gly Leu Ser Arg Thr Ala Gly
785 790 795 800
Leu Arg Ala Gly Gln Arg Leu Lys Leu Thr Gly Glu Val Glu Thr Thr
805 810 815
Ser Lys Val Ser Ala Lys Asn Thr Lys Glu Glu Thr Pro Glu Thr Tyr
820 825 830
Thr Val Lys Ser Gly Asp Ser Leu Gly Asn Ile Ala Asn Arg Tyr His
835 840 845
Leu Gln Leu Asp Tyr Leu Ala Ala Leu Asn Gly Leu Ser Arg Asn Ser
850 855 860
Asn Val Arg Val Gly Gln Arg Leu Lys Leu Thr Gly Asp Leu Pro Thr
865 870 875 880
Val Glu Thr Ala Lys Thr Asp Thr Ala Lys Ser Ser Pro Lys Ala Val
885 890 895
Val Ala Gly Lys Asn Thr Glu Lys Tyr Thr Val Lys Ala Gly Glu Ser
900 905 910
Leu Asn Ala Ile Ala Ser Arg Ala Gly Ile Ser Val Arg Glu Leu Ala
915 920 925
Glu Met Asn Ala Leu Lys Ala Asn Ala Asn Leu Gln Arg Gly Gln Asn
930 935 940
Ile Val Ile Pro Lys Thr Val Val Glu Tyr Lys Val Lys Arg Gly Asp
945 950 955 960
Thr Leu Ile Gly Leu Ala Ser Lys Tyr Gly Leu Glu Thr Thr Leu Leu
965 970 975
Ala Glu Leu Asn Asn Leu Thr Pro Ser Thr Gln Leu Arg Ile Gly Asp
980 985 990
Ile Ile Lys Val Pro Asn Leu
995
<210> 89
<211> 519
<212> PRT
<213> Acinetobacter baumannii
<400> 89
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1 5 10 15
Leu Ile Lys Gln Arg Ile Gly Asp Leu Asp Thr Ser Ala Thr Ala Lys
20 25 30
Asn Glu Gly Thr Ile Val Met Val Ser Asp Gly Ile Val Arg Ile His
35 40 45
Gly Leu Ala Asp Ala Met Tyr Gly Glu Met Ile Glu Phe Asp Gly Gly
50 55 60
Leu Phe Gly Met Ala Leu Asn Leu Glu Gln Asp Ser Val Gly Ala Val
65 70 75 80
Val Leu Gly Asn Tyr Leu Ser Leu Gln Glu Gly Gln Lys Ala Arg Cys
85 90 95
Thr Gly Arg Val Leu Glu Val Pro Val Gly Pro Glu Leu Leu Gly Arg
100 105 110
Val Val Asp Ala Leu Gly Asn Pro Ile Asp Gly Lys Gly Pro Ile Asp
115 120 125
Ala Lys Leu Thr Asp Ala Val Glu Lys Val Ala Pro Gly Val Ile Trp
130 135 140
Arg Gln Ser Val Asp Glu Pro Val Gln Thr Gly Tyr Lys Ser Val Asp
145 150 155 160
Thr Met Ile Pro Val Gly Arg Gly Gln Arg Glu Leu Ile Ile Gly Asp
165 170 175
Arg Gln Thr Gly Lys Thr Ala Met Ala Ile Asp Ala Ile Ile Ala Gln
180 185 190
Lys His Ser Gly Ile Lys Cys Val Tyr Val Ala Ile Gly Gln Lys Gln
195 200 205
Ser Thr Ile Ala Asn Val Val Arg Lys Leu Glu Glu Thr Gly Ala Met
210 215 220
Ala Tyr Thr Thr Val Val Ala Ala Ala Ala Ala Asp Pro Ala Ala Met
225 230 235 240
Gln Tyr Leu Ala Pro Tyr Ser Gly Cys Thr Met Gly Glu Tyr Phe Arg
245 250 255
Asp Arg Gly Glu Asp Ala Leu Ile Ile Tyr Asp Asp Leu Ser Lys Gln
260 265 270
Ala Val Ala Tyr Arg Gln Ile Ser Leu Leu Leu Arg Arg Pro Pro Gly
275 280 285
Arg Glu Ala Tyr Pro Gly Asp Val Phe Tyr Leu His Ser Arg Leu Leu
290 295 300
Glu Arg Ala Ser Arg Val Ser Ala Asp Tyr Val Glu Lys Phe Thr Asn
305 310 315 320
Gly Ala Val Thr Gly Gln Thr Gly Ser Leu Thr Ala Leu Pro Ile Ile
325 330 335
Glu Thr Gln Ala Gly Asp Val Ser Ala Phe Val Pro Thr Asn Val Ile
340 345 350
Ser Ile Thr Asp Gly Gln Ile Phe Leu Glu Thr Ser Leu Phe Asn Ala
355 360 365
Gly Ile Arg Pro Ala Val Asn Ala Gly Ile Ser Val Ser Arg Val Gly
370 375 380
Gly Ser Ala Gln Thr Lys Ile Ile Lys Lys Leu Ser Gly Gly Ile Arg
385 390 395 400
Thr Ala Leu Ala Gln Tyr Arg Glu Leu Ala Ala Phe Ala Gln Phe Ala
405 410 415
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420 425 430
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435 440 445
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450 455 460
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465 470 475 480
Phe Arg Ser Glu Tyr Ala Pro Leu Met Lys Gln Ile Asp Glu Thr Gly
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<210> 90
<400> 90
000
<210> 91
<400> 91
000
<210> 92
<400> 92
000
<210> 93
<400> 93
000
<210> 94
<400> 94
000
<210> 95
<400> 95
000
<210> 96
<400> 96
000
<210> 97
<400> 97
000
<210> 98
<400> 98
000
<210> 99
<400> 99
000
<210> 100
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> primer forward
<400> 100
gctaattggt gaaggtagtc 20
<210> 101
<211> 20
<212> DNA
<213> Artificial Sequence
<220>
<223> primer reverse
<400> 101
gacgaatcgt ttgaatctgc 20

Claims (15)

1.一种疫苗组合物,其适用于预防性治疗由鲍氏不动杆菌菌株在哺乳动物体内引起的感染,所述疫苗组合物包含:
a.脂多糖缺失的鲍氏不动杆菌菌株的耐粘菌素突变体,其特征在于选自由lpxA、lpxC、lpxD组成的组的基因部分或完全失活;和/或
b.衍生自如上段a)中定义的脂多糖缺失的鲍氏不动杆菌菌株的耐粘菌素突变体的外膜囊泡。
2.根据权利要求1所述的疫苗组合物,其特征在于,其中所述脂多糖缺失的鲍氏不动杆菌菌株的lpxD基因的核苷酸序列部分缺失。
3.根据权利要求1或2所述的疫苗组合物,其特征在于,所述疫苗还包含选自以下序列的重组多肽:
a)氨基酸序列SEQ ID NO.27或其片段,其中术语片段在此理解为生物活性片段,其选自SEQ ID NO.1至SEQ ID NO.11或其任何组合,或与序列SEQ ID NO.1至SEQ ID NO.11具有至少85%一致性的氨基酸序列;和/或
b)氨基酸序列SEQ ID No.28或其片段,其中术语片段在此理解为生物活性片段,其选自SEQ ID NO.12至SEQ ID NO.23或其任何组合,或与氨基酸序列SEQ ID NO.12至SEQ IDNO.23具有至少85%一致性的序列。
4.根据权利要求1或2所述的疫苗组合物,其特征在于,所述疫苗组合物还包含选自SEQID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQID NO:41、SEQ ID NO:42、SEQ ID NO:43、SEQ ID NO:44、SEQ ID NO:45、SEQ ID NO:46、SEQID NO:47、SEQ ID NO:48、SEQ ID NO:49、SEQ ID NO:50、SEQ ID NO:51、SEQ ID NO:52、SEQID NO:53、SEQ ID NO:54、SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:57、SEQ ID NO:58、SEQID NO:59、SEQ ID NO:60、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:63、SEQ ID NO:64、SEQID NO:65、SEQ ID NO:66、SEQ ID NO:67、SEQ ID NO:68、SEQ ID NO:69、SEQ ID NO:70、SEQID NO:71、SEQ ID NO:72、SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQID NO:77、SEQ ID NO:78、SEQ ID NO:79、SEQ ID No:80、SEQ ID NO:81、SEQ ID NO:82、SEQID NO:83、SEQ ID NO:84、SEQ ID NO:85、SEQ ID NO:86、SEQ ID NO:87、SEQ ID NO:88、SEQID NO:89或其组合的鲍氏不动杆菌的纯化的外膜蛋白序列。
5.根据权利要求1或2所述的疫苗组合物,其特征在于,所述疫苗还包含SEQ ID NO.24或25的融合重组多肽或由SEQ ID NO.26的核酸分子编码的融合重组多肽。
6.根据权利要求1或2所述的疫苗组合物,其特征在于,所述脂多糖缺失的鲍氏不动杆菌菌株包含以下核苷酸序列:该核苷酸序列能够编码氨基酸序列SEQ ID Nos.1-89中的任何一个,以使所述菌株能够产生氨基酸序列SEQ ID Nos.1-89中的任何一个的外源表达。
7.根据权利要求1或2所述的疫苗组合物,其特征在于,所述疫苗组合物还包含载体,所述载体包含核苷酸序列,该核苷酸序列能够编码并且表达氨基酸序列SEQ ID Nos.1-89中的任何一个。
8.根据权利要求1或2所述的疫苗组合物,其特征在于,所述脂多糖缺失的鲍氏不动杆菌菌株被灭活。
9.根据权利要求1或2所述的疫苗组合物,其特征在于,所述脂多糖缺失的鲍氏不动杆菌菌株来自ATCC菌株19606。
10.根据权利要求1或2所述的疫苗组合物,其中,该疫苗组合物用于预防性治疗由鲍氏不动杆菌在哺乳动物体内引起的感染。
11.根据权利要求10所述的疫苗组合物,其中,所述哺乳动物为人类。
12.一种疫苗组合物,其包含分离的抗体或其片段,所述抗体或其片段是在用权利要求1或2所述的疫苗组合物对哺乳动物进行免疫处理后获得的,或者能够在进行该免疫处理后获得。
13.根据权利要求12所述的疫苗组合物在制备治疗由鲍氏不动杆菌在哺乳动物中引起的感染的药物上的用途。
14.根据权利要求13所述的用途,其中所述哺乳动物为人类。
15.脂多糖缺失的鲍氏不动杆菌菌株和/或由其衍生的外膜囊泡在生产能够结合所述菌株和/或外膜囊泡的抗体或其片段上的用途,所述脂多糖缺失的鲍氏不动杆菌菌株的特征在于选自由lpxA、lpxC、lpxD组成的组的基因的部分或完全失活。
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