Insertion of bacteria type III secretion proteins into target cell membrane

肠源性和肠出血性大肠埃希氏菌引起大量以严重和持续性腹泻为特征的食物和水传播的胃肠道疾病。这些细菌含有一组独特的毒力蛋白，称为III型分泌系统(TTS)。TTSS由两类指定的转位蛋白和效应蛋白组成。转位蛋白参与形成一种称为针状复合体的分子隧道，该复合体从细菌细胞生长出来，与肠道上皮细胞接触。一旦针状复合体与上皮细胞表面对接，细菌就会释放一系列称为穿孔蛋白，它穿透宿主细胞的质膜，允许细菌将效应器蛋白直接注入上皮细胞。这些效应器蛋白的作用是改变上皮细胞的结构和细胞功能，使细菌能够附着和定植于肠道。这个过程的一个关键方面还没有被很好地理解，那就是细菌形成孔蛋白是如何选择性地穿透上皮细胞膜的。这项建议的目的是研究与膜孔形成有关的分子事件，该膜孔允许细菌蛋白质直接转移到上皮细胞中。

Enteropathogenic and enterohemorrhagic E. coli are responsible for a vast number of food and water borne gastrointestinal diseases that are characterized by severe and persistent diarrhea.  These bacteria contain a unique group of virulence proteins called the type III secretion system (TTS).  The TTSS consists of two classes of bacterial protein designated translocator and effector proteins.  The translocator proteins are involved in forming a molecular tunnel called a needle complex that grows out from the bacterial cell to make contact with the epithelial cells that line the intestinal tract.  Once the needle complex docks with the epithelial cell surface the bacteria release a set of called the pore forming proteins that penetrate the plasma membrane of the host cell allowing the bacteria to inject the effector proteins directly into the epithelial cell.  These effector proteins act to modify both the structure and cellular function of the epithelial cell to allow bacteria to attach and colonize the intestine. A key aspect of this process that is not well understood is how the bacterial pore forming proteins selectively penetrate the epithelial cell membrane. The aim of this proposal is to study is to examine the molecular event involve in formation of the membrane pore that permits bacterial proteins to be translocated directly into the epithelial cell.