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宿主依赖性差异表达的因子 H 结合蛋白、它们与因子 H 的亲和力以及莱姆病和回归热螺旋体的补体逃避。

Host-dependent differential expression of factor H binding proteins, their affinity to factor H and complement evasion by Lyme and relapsing fever borreliae.

机构信息

Laboratory of Biomedical Microbiology and Immunology, University of Veterinary Medicine and pharmacy, Košice, Slovakia.

出版信息

Vet Microbiol. 2011 Mar 24;148(2-4):341-7. doi: 10.1016/j.vetmic.2010.09.026.

Abstract

Binding of complement factor H is crucial for the resistance of Borrelia to complement-mediated lysis. This study was aimed to assess the correlation between the expression of fH binding proteins (FHBPs) during the early phase of infection (48 h after the entry of Borrelia into the blood circulation) and complement resistance of the Borrelia genus. As expected, B. afzelii, B. burgdorferi sensu stricto and B. garinii (Serotype 4, PBi) showed resistance to complement mediated lysis when incubated with human and dog complement, which coincided with the significantly higher expression (P<0.05) of the FHBPs. Similarly, B. coriaceae showed resistance to cattle complement. In non-reservoir hosts borreliae failed to induce expression of FHBPs within 48 h of complement challenge, and did not survive. It is important to note that not only the expression of FHBP but also their binding to fH is required for borrelial resistance to the complement. fH binding may depend on the coiled-coil (CC) motifs observed in the FHBPs, especially at the C terminus. A loss of the C-terminal CC motif in BgCRASP-1 of SKT-1 strain was found in in-silico CC prediction, and may be coupled with SKT-1's inability to bind factor H and evade complement-mediated attack. In contrast, the C-terminal CC motif was observed (P - 1.0) in BgCRASP-1 of PBi that may contributed to its factor H binding and human complement resistance.

摘要

补体因子 H 的结合对于伯氏疏螺旋体抵抗补体介导的裂解至关重要。本研究旨在评估感染早期(伯氏疏螺旋体进入血液循环后 48 小时)fH 结合蛋白(FHBPs)的表达与伯氏疏螺旋体属的补体抗性之间的相关性。正如预期的那样,当用人和狗补体孵育时,B. afzelii、B. burgdorferi sensu stricto 和 B. garinii(血清型 4,PBi)表现出对补体介导的裂解的抗性,这与 FHBPs 的表达显著增加(P<0.05)相一致。同样,B. coriaceae 对牛补体具有抗性。在非贮存宿主中,伯氏疏螺旋体在补体挑战后 48 小时内未能诱导 FHBPs 的表达,并且无法存活。需要注意的是,不仅 FHBPs 的表达,而且它们与 fH 的结合对于伯氏疏螺旋体抵抗补体也是必需的。fH 结合可能取决于在 FHBPs 中观察到的卷曲螺旋(CC)基序,尤其是在 C 末端。在 SKT-1 菌株的 BgCRASP-1 中,在计算机预测的 CC 中发现 C 末端 CC 基序缺失,这可能与 SKT-1 无法结合因子 H 和逃避补体介导的攻击有关。相比之下,在 PBi 的 BgCRASP-1 中观察到(P-1.0)C 末端 CC 基序,这可能有助于其与因子 H 的结合和对人补体的抗性。

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