Coordinated expression of Borrelia burgdorferi complement regulator-acquiring surface proteins during the Lyme disease Spirochete's mammal-tick infection cycle

Coordinated expression of Borrelia burgdorferi complement regulator-acquiring surface proteins during the Lyme disease Spirochete's mammal-tick infection cycle
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DOI:
10.1128/iai.00604-07
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发表时间:
2007-09-01
影响因子:
3.1
通讯作者:
Stevenson, Brian
Stevenson, Brian
中科院分区:
医学2区
文献类型:
--
作者:
Bykowski, Tomasz;Woodman, Michael E.;Stevenson, Brian

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莱姆病螺旋体伯氏疏螺旋体在很大程度上能抵抗宿主的替代补体激活途径的杀伤。这些细菌的一种可能的抵抗机制是用宿主补体调节因子,如因子H,覆盖其表面。已鉴定出五种对因子H具有亲和力的不同的伯氏疏螺旋体外表面蛋白:由cspA编码的补体调节因子获取表面蛋白1(BbCRASP - 1);由cspZ编码的BbCRASP - 2;以及三种密切相关的蛋白,分别由erpP、erpC和erpA编码的BbCRASP - 3、 - 4和 - 5。我们现在对最近鉴定的BbCRASP - 2和cspZ在伯氏疏螺旋体整个感染周期中的表达模式进行分析,并对BbCRASP - 1和由erp编码的BbCRASPs进行新的分析。我们的结果,结合早期研究的数据,表明BbCRASP - 2主要在已确立的哺乳动物感染期间产生,而BbCRASP - 1在蜱到哺乳动物以及哺乳动物到蜱的传播阶段产生,但在已确立的哺乳动物感染期间不产生,并且Erp - BbCRASPs从感染蜱传播到哺乳动物时开始产生,直到它们后来被其他取食蜱获取。相对于在哺乳动物感染期间观察到的mRNA水平,在实验室培养基中培养时cspZ的转录和BbCRASP - 2的合成受到严重抑制,并且cspZ的表达受培养温度和pH的影响,这些观察结果将有助于确定伯氏疏螺旋体控制这种与疏螺旋体感染相关蛋白表达所采用的机制。
The Lyme disease spirochete, Borrelia burgdorferi, is largely resistant to being killed by its hosts' alternative complement activation pathway. One possible resistance mechanism of these bacteria is to coat their surfaces with host complement regulators, such as factor H. Five different B. burgdorferi outer surface proteins having affinities for factor H have been identified: complement regulator-acquiring surface protein 1 (BbCRASP-1), encoded by cspA; BbCRASP-2, encoded by cspZ; and three closely related proteins, BbCRASP-3, -4, and -5, encoded by erpP, erpC, and erpA, respectively. We now present analyses of the recently identified BbCRASP-2 and cspZ expression patterns throughout the B. burgdorferi infectious cycle, plus novel analyses of BbCRASP-1 and erp-encoded BbCRASPs. Our results, combined with data from earlier studies, indicate that BbCRASP-2 is produced primarily during established mammalian infection, while BbCRASP-1 is produced during tick-to-mammal and mammal-to-tick transmission stages but not during established mammalian infection, and Erp-BbCRASPs are produced from the time of transmission from infected ticks into mammals until they are later acquired by other feeding ticks. Transcription of cspZ and synthesis of BbCRASP-2 were severely repressed during cultivation in laboratory medium relative to mRNA levels observed during mammalian infection, and cspZ expression was influenced by culture temperature and pH, observations which will assist identification of the mechanisms employed by B. burgdorferi to control expression of this borrelial infection-associated protein.