Pseudomonas aeruginosa-induced host cell pathogenesis

铜绿假单胞菌诱导的宿主细胞发病机制

• 批准号: 6583942
• 负责人: SASHA H SHAFIKHANI
• 金额: $ 4.64万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6583942
• 关键词: Pseudomonas aeruginosa; apoptosis; bacteria infection mechanism; host organism interaction; laboratory mouse; molecular cloning; postdoctoral investigator

DESCRIPTION (provided by applicant): Pseudomonas aeruginosa (PA) is an opportunistic gram-negative pathogen responsible for a large number of nosocomial infections. Dr. Joanne Engel and her group have shown that PA103 induces apoptotic-like cell death in epithelial cells and macrophages by a Type III Secretion System (TTSS)-dependent mechanism. Consistent with the results of others, They have found this to be a Fas ligand- and Fas receptor-dependent process. We propose that PA-induced apoptosis occurs either by (A) direct translocation of a bacterial effector into the host cell (PAF, for Pseudomonas Apoptosis Factor) by the TTSS, resulting in activation of Fas-dependent apoptosis or by (B) direct induction of Fas-dependent apoptosis by one or more components of the type III translocation apparatus itself. We will identify the mechanism by which PAl03 induces TTS-dependent apoptotic-like cell death in eukaryotic cells. We will initially use genetic and proteomic approaches to identify a putative apoptosis-inducing type III secreted effector molecule. We may also test the alternative hypothesis that the TTSS itself is responsible for the induction of apoptosis by PA. We will express the PA TTSS in a Yersinia strain that lacks the plasmid encoded TTSS and test for restoration of apoptosis-inducing activity.

描述（由申请人提供）：铜绿假单胞菌（PA）是一种机会性的革兰氏阴性病原体，负责大量的医生感染。 Joanne Engel博士和她的小组表明，PA103通过III型分泌系统（TTSS）依赖性机制诱导上皮细胞和巨噬细胞中的凋亡样细胞死亡。与他人的结果一致，他们发现这是FAS配体和FAS受体依赖性过程。我们提出，PA诱导的凋亡是通过（a）通过TTSS直接转移细菌效应子到宿主细胞中（PAF，用于伪瘤凋亡因子），从而导致FAS依赖性凋亡激活，或者通过（B）直接诱导FAS依赖性凋亡依赖FAS依赖性局部或更多组合型III II类型III IIII II II II II II II II。我们将确定PAL03在真核细胞中诱导TTS依赖性凋亡样细胞死亡的机制。我们最初将使用遗传和蛋白质组学方法来识别诱导的III型分泌效应子分子。我们还可以检验TTSS本身负责PA诱导凋亡的替代假设。我们将以缺乏质粒编码的TTSS并恢复凋亡诱导活性的质粒菌株中表达PA TTSS。