Complement evasion by relapsing fever spirochetes

回归热螺旋体逃避补体

• 批准号: 6940966
• 负责人: KELLEY M HOVIS
• 金额: $ 3.07万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-25 至 2007-04-24
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6940966
• 关键词: Borrelia; DNA primers; Lyme disease; alternative complement pathway; bacteria infection mechanism; bacterial proteins; binding proteins; borreliosis; chemical cleavage; complement; complement pathway regulation; gene induction /repression; host organism interaction; laboratory mouse; molecular pathology; molecular site; opsonin; pathologic process; plasmids; polymerase chain reaction; predoctoral investigator; protein binding; protein protein interaction; recombinant proteins; site directed mutagenesis; transfection /expression vector

DESCRIPTION (provided by applicant): The Borrelia are the causative agents of several important human and animal infections including Lyme disease and relapsing fever. Recent studies from our lab and others have demonstrated that some species of the Lyme disease spirochetes bind the complement regulatory protein, factor H (fH). FH bound on the cell surface is able to interact with factor I and facilitate the efficient cleavage of the critical complement component C3b. In the context of bacterial pathogenesis, this cleavage event serves to protect the bacteria from opsonization and the alternate complement cascade. The relapsing fever spirochetes (RFS) are able to persist in their mammalian hosts for extended periods of time. Some species achieve high cell densities in the blood while others tend to invade the CNS. The ability to survive in the blood suggests that these bacteria are also able to circumvent complement. We have recently identified and characterized a new and novel fH binding protein (FHBP) in B. hermsii that we call FhbA (fH-binding protein A). In this proposal we will investigate the molecular interactions between FhbA and human fH and investigate the contribution of FhbA in pathogenesis through gene inactivation.

描述（由申请人提供）：硼酸盐是几种重要的人类和动物感染的病因，包括莱姆病和复发性发烧。我们实验室和其他人的最新研究表明，莱姆病螺旋体的某些物种结合了补体调节蛋白因子H（FH）。绑定在细胞表面上的FH能够与因子I相互作用，并促进了临界补体成分C3B的有效切割。在细菌发病机理的背景下，这种裂解事件可保护细菌免受打击和替代补体级联反应。复发性发烧螺旋体（RFS）能够长时间持续在其哺乳动物宿主中。一些物种在血液中达到高细胞密度，而另一些物种倾向于侵入中枢神经系统。血液中生存的能力表明这些细菌也能够绕过补体。我们最近确定并表征了B. hermsii中一种新的新型FH结合蛋白（FHBP），我们称为FHBA（FH结合蛋白A）。在此提案中，我们将研究FHBA与人FH之间的分子相互作用，并研究FHBA通过基因失活而在发病机理中的贡献。