Insertion of bacteria type III secretion proteins into target cell membrane

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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.