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: 6877748
• 负责人: SASHA H SHAFIKHANI
• 金额: $ 5.15万
• 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/6877748
• 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（由申请方提供）：铜绿假单胞菌（PA）是一种机会性革兰氏阴性病原体，可引起大量院内感染。Joanne Engel博士和她的研究小组已经表明，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嗜酸细胞样细胞死亡。与其他人的结果一致，他们发现这是一个Fas配体和Fas受体依赖性过程。我们认为PA诱导的细胞凋亡是通过（A）TTSS将细菌效应子直接转运到宿主细胞（PAF，即假单胞菌凋亡因子）中，导致Fas依赖性细胞凋亡的激活，或（B）III型转运装置本身的一种或多种成分直接诱导Fas依赖性细胞凋亡而发生的。我们将鉴定PA103在真核细胞中诱导TTS依赖性类凋亡细胞死亡的机制。我们将首先使用遗传学和蛋白质组学方法来确定一个假定的骨化诱导III型分泌效应分子。我们还可以测试另一种假设，即TTSS本身是负责诱导PA的凋亡。我们将在缺乏质粒编码的TTSS的耶尔森氏菌菌株中表达PA TTSS，并测试诱导溶血活性的恢复。