Dynamic modification of microtubule-dependent transport by Salmonella effector proteins

沙门氏菌效应蛋白对微管依赖性转运的动态修饰

• 批准号: 5407652
• 负责人: Professor Dr. Michael Hensel
• 金额: --
• 依托单位: Arbeitsgruppe Mikrobiologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2003
• 资助国家: 德国
• 起止时间: 2002-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5407652?language=en
• 关键词: Dynamic; modification; microtubule; dependent; transport

The intracellular pathogen Salmonella enterica utilizes a type III secretion system encoded by Salmonella Pathogenicity Island 2 to translocate effector proteins that manipulate infected host cells. We have recently identified SseF and SseG as two novel effector proteins that interfere with the host cell cytoskeleton. In contrast to most other effector proteins, SseF and SseG are not interacting with the actin cytoskeleton but are rather targeted to microtubules. We observed that translocation of SseF and SseG induces the bundling of microtubules, and affects the aggregation of endosomal vesicles along microtubules. These observations lead to the hypothesis that intracellular Salmonella modify the transport along microtubules in order to generate an intracellular niche that is permissive for bacterial proliferation. The proposed project aims to investigate the interaction of effector proteins SseF and SseG with microtubule functions in detail. Host cell proteins interacting with effector protein SseF and SseG will be identified by complementary molecular approaches. The molecular interactions will be studied in detail and functional domains of the SseF and SseG will be defined. It is also planned to establish functional assays to analyse the interference with microtubule-dependent transport functions. This project will ultimately contribute to the understanding of a novel form of host-pathogen interaction and reveal how normal eukaryotic cell functions are manipulated by bacterial virulence determinants.

胞内病原体肠沙门氏菌利用由沙门氏菌致病性岛2编码的III型分泌系统转运操纵受感染宿主细胞的效应蛋白。我们最近发现SseF和SseG是两种干扰宿主细胞骨架的新型效应蛋白。与大多数其他效应蛋白相反，SseF和SseG不与肌动蛋白细胞骨架相互作用，而是靶向微管。我们观察到SseF和SseG的易位诱导了微管的捆绑，并影响了内体囊泡沿微管的聚集。这些观察结果导致了一个假设，即细胞内沙门氏菌改变沿微管的运输，以产生一个允许细菌增殖的细胞内生态位。本项目旨在详细研究效应蛋白SseF和SseG与微管功能的相互作用。与效应蛋白SseF和SseG相互作用的宿主细胞蛋白将通过互补的分子方法进行鉴定。我们将详细研究分子间的相互作用，并定义SseF和SseG的功能域。还计划建立功能分析来分析与微管依赖的运输功能的干扰。该项目将最终有助于理解宿主-病原体相互作用的一种新形式，并揭示正常真核细胞功能是如何被细菌毒力决定因素操纵的。