Molecular Analysis of the Chlamydia trachomatis virulence factor Tarp

总结： 在美国，专性细胞内细菌沙眼衣原体导致大量发病， 国际吧梭名为Tarp的沙眼效应子，用于移位肌动蛋白募集蛋白是候选者 毒力因子Tarp被宿主细胞激酶酪氨酸磷酸化，并与肌动蛋白募集有关 在C.沙眼进入。迄今为止检查的衣原体属的所有参考和临床分离株 tarP基因我们已经鉴定和生物化学表征了四个Tarp蛋白结构域，包括： iii）G-肌动蛋白结合和成核结构域， 和iv）两个F-肌动蛋白结合和捆绑结构域。我们假设特定的Tarp域是必需的 细菌进入和/或衣原体发展。我们将通过以下方式检验这一假设：1）检查 Tarp介导的肌动蛋白束力学; 2）分析C.沙眼衣原体tarp突变体和补体， 表达Tarp结构域缺失，用于衣原体入侵宿主细胞和发育和3）。探讨 在小鼠感染模型中对tarP的需求。阐明了C. 沙眼衣原体启动成功感染可能提供线索，可以应用于新的治疗方法， 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.