Complement regulator-acquiring surface protein 1 imparts resistance to human serum in Borrelia burgdorferi
Complement regulator-acquiring surface protein 1 imparts resistance to human serum in Borrelia burgdorferi
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DOI：
10.4049/jimmunol.175.5.3299
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发表时间：
2005-09-01
影响因子：
4.4
通讯作者：
Akins, DR
中科院分区：
文献类型：
--
作者：
Brooks, CS;Vuppala, SR;Akins, DR
因子H和因子H样蛋白1（FH/FHL-1）是负调节补体旁路途径的可溶性血清蛋白。现在已经充分认识到，许多致病性细菌，包括伯氏疏螺旋体，在它们的细胞表面上结合FH/FHL-1以在感染期间逃避补体介导的破坏。最近，有人提出，B。burgdorferi开放阅读框bbA 68，称为补体调节获得表面蛋白1（CRASP-1），编码B的主要FH/FHL-1结合蛋白。burgdorferi。但是，因为在B表面已经鉴定出了几种其他的蛋白质。尽管CRASP-1也可以结合FH/FHL-1，但目前还不清楚CRASP-1在血清抗性中起什么作用。为了检查CRASP-I在血清抗性中的贡献，我们产生了B。该突变体不表达CRASP-1。B。发现命名为B31 cF-CRASP-1的伯氏疏螺旋体CRASP-1突变体与已知对人血清敏感的伽氏疏螺旋体50野生型菌株一样对人血清敏感。为了进一步研究CRASP-1在血清抗性中的作用，我们还创建了从天然B表达CRASP-1的穿梭载体。将其命名为pKFSS-1：：CRASP-1。当pKFSS-1：：CRASP-1构建体转化到B中时，恢复了BurgdorferiB 31 cF-CRASP-1突变体、野生型血清抗性水平。此外，当pKFSS 4：：CRASP-1转化到血清敏感的B中时，garinii 50分离株，该菌株的人血清抗性被赋予与野生型B不可区分的水平。burgdorferi。综合数据使我们得出结论，CRASP-1表达对于B是必需的。抵抗人类血清的杀死。
Factor H and factor H-like protein 1 (FH/FHL-1) are soluble serum proteins that negatively regulate the alternative pathway of complement. It is now well recognized that many pathogenic bacteria, including Borrelia burgdorferi, bind FH/FHL-1 on their cell surface to evade complement-mediated destruction during infection. Recently, it was suggested that B. burgdorferi open reading frame bbA68, known as complement regulator-acquiring surface protein 1 (CRASP-1), encodes the major FH/FHL-1-binding protein of B. burgdorferi. However, because several other proteins have been identified on the surface of B. burgdorferi that also can bind FH/FHL-1, it is presently unclear what role CRASP-1 plays in serum resistance. To examine the contribution of CRASP-I in serum resistance, we generated a B. burgdorferi mutant that does not express CRASP-1. The B. burgdorferi CRASP-1 mutant, designated B31cF-CRASP-1, was found to be as susceptible to human serum as a wild-type strain of Borrelia garinii 50 known to be sensitive to human serum. To further examine the role of CRASP-1 in serum resistance, we also created a shuttle vector that expresses CRASP-1 from the native B. burgdorferi gene, which was designated pKFSS-1::CRASP-1. When the pKFSS-1::CRASP-1 construct was transformed into the B. burgdorferi B31cF-CRASP-1 mutant, wild-type levels of serum resistance were restored. Additionally, when pKFSS4::CRASP-1 was transformed into the serum-sensitive B. garinii 50 isolate, human serum resistance was imparted on this strain to a level indistinguishable from wild-type B. burgdorferi. The combined data led us to conclude that CRASP-1 expression is necessary for B. burgdorferi to resist killing by human serum.