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 全世界。沙眼衣原体称为转位肌动蛋白招募蛋白Tarp的效应器是候选 毒力因子。TARP是被宿主细胞激酶磷酸化的酪氨酸，与肌动蛋白募集有关 在沙眼衣原体进入期间。到目前为止检查的所有衣原体参考和临床分离株 TARP基因。我们已经确定了四个Tarp蛋白结构域并进行了生化特征分析，包括：i)a 磷酸化结构域II)富含Pro的寡聚化结构域III)G-肌动蛋白结合和核化结构域， 以及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验证这一假设：1)检查 TARP介导的肌动蛋白束的机制，2)分析沙眼衣原体TARP突变体和补体 表达衣原体侵入宿主细胞和发育的TARP结构域缺失。调查 在小鼠感染模型中对TARP的要求。阐明了C. 沙眼衣原体引发成功感染可能提供线索，可应用于新的治疗方法 对这种多产病原体的干预。

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.