首页> 外文期刊>Infection and immunity >The Borrelia hermsii Factor H Binding Protein FhbA Is Not Required for Infectivity in Mice or for Resistance to Human Complement In Vitro
【24h】

The Borrelia hermsii Factor H Binding Protein FhbA Is Not Required for Infectivity in Mice or for Resistance to Human Complement In Vitro

机译:对于小鼠的感染性或体外对人补体的抗性,不需要芽孢疏螺旋体H结合蛋白FhbA

获取原文
           

摘要

The primary causative agent of tick-borne relapsing fever in North America is Borrelia hermsii. It has been hypothesized that B. hermsii evades complement-mediated destruction by binding factor H (FH), a host-derived negative regulator of complement. In vitro, B. hermsii produces a single FH binding protein designated FhbA (FH binding protein A). The properties and ligand binding activity of FhbA suggest that it plays multiple roles in pathogenesis. It binds plasminogen and has been identified as a significant target of a B1b B cell-mediated IgM response in mice. FhbA has also been explored as a potential diagnostic antigen for B. hermsii infection in humans. The ability to test the hypothesis that FhbA is a critical virulence factor in vivo has been hampered by the lack of well-developed systems for the genetic manipulation of the relapsing fever spirochetes. In this report, we have successfully generated a B. hermsii fhbA deletion mutant (the B. hermsii YORΔfhbA strain) through allelic exchange mutagenesis. Deletion of fhbA abolished FH binding by the YORΔfhbA strain and eliminated cleavage of C3b on the cell surface. However, the YORΔfhbA strain remained infectious in mice and retained resistance to killing in vitro by human complement. Collectively, these results indicate that B. hermsii employs an FhbA/FH-independent mechanism of complement evasion that allows for resistance to killing by human complement and persistence in mice.
机译:北美tick传播复发热的主要病原体是黑氏疏螺旋体。据推测,贺氏芽孢杆菌通过结合因子H(FH)逃避补体介导的破坏,结合因子H是宿主衍生的补体负调节剂。 在体外,疱疹双歧杆菌产生一种称为FhbA的FH结合蛋白(FH结合蛋白A)。 FhbA的性质和配体结合活性表明,它在发病机理中起着多种作用。它结合纤溶酶原,已被确定为小鼠中B1b B细胞介导的IgM反应的重要靶标。 FhbA也已被开发为人类感染埃希氏杆菌的潜在诊断抗原。由于缺乏对复发性发热螺旋体进行基因操作的完善系统,因此无法检验FhbA是体内关键毒力因子这一假说的能力。在本报告中,我们已经通过等位基因交换诱变成功地产生了一个赫氏芽孢杆菌 fhbA 缺失突变体(赫氏芽孢杆菌YORΔ fhbA 菌株)。删除 fhbA 消除了YORΔ fhbA 菌株的FH结合,消除了C3b在细胞表面的裂解。然而,YORΔ fhbA 株在小鼠中仍具有传染性,并保留了对人补体杀死体外的抗性。总体而言,这些结果表明,赫氏芽孢杆菌采用了FhbA / FH独立的补体逃逸机制,该机制可抵抗人类补体的杀伤和在小鼠中的持久性。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号