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Molecular Analysis of the Chlamydia trachomatis virulence factor Tarp

沙眼衣原体毒力因子 Tarp 的分子分析

基本信息

批准号：
10219061
负责人：
Travis James Jewett
金额：
$ 55.17万
依托单位：
UNIVERSITY OF CENTRAL FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-28 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10219061
关键词：
Actins Affect Architecture Attenuated Bacteria Binding Biochemical Biology Bundling C3H/HeJ Mouse Cell Shape Cells Cervical Chlamydia Chlamydia trachomatis Clinical Collaborations Collection Complement Cytoskeleton Data Development Epithelial Cells Event F-Actin Fluorescence Foundations G Actin GTP-Binding Protein alpha Subunits, Gs Generations Genes Genetic Goals Human Infection Interruption Invaded Length Measures Mechanics Mediating Microfilaments Modeling Molecular Molecular Analysis Molecular Genetics Morbidity - disease rate Mus Pathogenesis Pathogenicity Phosphorylation Phosphotransferases Play Prevention Proline Protein Tyrosine Kinase Proteins Reporting Research Proposals Resources Role Sexually Transmitted Diseases Signal Transduction Spatial Distribution Technology Tertiary Protein Structure Testing Time Tyrosine Vaccines Virulence Virulence Factors biophysical properties bone genetic approach genetic regulatory protein high reward human tissue in vivo in vivo evaluation innovation insight mechanical properties microorganism microscopic imaging molecular mechanics mutant novel novel therapeutic intervention pathogen polymerization recruit tissue/cell culture tool

项目摘要

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.

总结：在美国，专性细胞内细菌沙眼衣原体导致大量发病，国际吧梭一种名为Tarp的沙眼衣原体效应子，用于转运肌动蛋白募集蛋白，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，用于衣原体侵入宿主细胞和发育;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会提供可应用于新型治疗方法的线索针对这种多产病原体的干预措施。