Molecular Analysis of the Chlamydia trachomatis virulence factor Tarp

摘要： 专性细胞内细菌沙眼衣原体在美国和美国造成大量发病 全世界。一种名为 Tarp 的沙眼衣原体效应器，用于易位肌动蛋白募集蛋白，是候选者 毒力因子。 Tarp 是由宿主细胞激酶磷酸化的酪氨酸，与肌动蛋白募集相关 沙眼衣原体进入期间。迄今为止检查的所有衣原体物种的参考和临床分离株 tarP 基因。我们已经鉴定出四个 Tarp 蛋白结构域并对其进行生化表征，包括： i) 磷酸化结构域 ii) 富含脯氨酸的寡聚化结构域 iii) G-肌动蛋白结合和成核结构域， iv) 两个 F-肌动蛋白结合和捆绑结构域。我们假设需要特定的 Tarp 域 用于细菌进入和/或衣原体发育。我们将通过以下方式检验这个假设：1）检验 Tarp 介导的肌动蛋白束的力学，2) 分析沙眼衣原体 tarp 突变体和补充 表达 Tarp 结构域缺失导致衣原体侵入宿主细胞和发育；3)。调查 小鼠感染模型中对 tarP 的要求。阐明 C. 所采用的分子机制 沙眼衣原体启动成功的感染可能提供可应用于新治疗方法的线索 针对这种多产病原体的干预措施。

SUMMARY: The obligate intracellular bacterium Chlamydia trachomatis causes substantial morbidity in the US and worldwide. A C. trachomatis effector called Tarp for translocated actin recruiting protein is a candidate virulence factor. Tarp is tyrosine phosphorylated by a host cell kinase and is associated with actin recruitment during C. trachomatis entry. All reference and clinical isolates of Chlamydiae species examined to date harbor the tarP gene. We have identified and biochemically characterized four Tarp protein domains including: i) a phosphorylation domain ii) a proline rich oligomerization domain iii) a G-actin binding and nucleating domain, and iv) two F-actin binding and bundling domains. We hypothesize that specific Tarp domains are required for bacterial entry and/or chlamydial development. We will test this hypothesis by: 1) examining the mechanics of Tarp mediated actin bundles, 2) analyzing C. trachomatis tarp mutants and complements that express Tarp domain deletions for chlamydial invasion of host cells and development and 3). Investigate the requirement for tarP in a mouse infection model. Elucidation of the molecular mechanisms employed by C. trachomatis to initiate a successful infection may provide clues that can be applied to novel therapeutic interventions for this prolific pathogen.