Salmonella enteric is a facultative intracellular pathogen that causes a number of diseases including gastroenteritis and typhoid fever. The pathogenesis of Salmonella enteric requires two type III secretion systems (TTSS), specialized organelles that mediate delivery of bacterial virulence effectors proteins from the bacteria to the host cell. Effectors function to promote bacterial survival and colonization. Salmonella typhimurium (S. typhimurium) encodes a family of three leucine-rich repeats (LRR)-containing effectors: SspH1, SspH2, and Slrp. S. typhimurium strains carrying deletion mutations in slrp or in both sspH1 and sspH2 were reduced in virulence in animal models of infection, indicating that these effectors are required for normal pathogenesis. Determining the function of these LRR effectors proteins will provide insights into Salmonella virulence and may lead to the development of novel treatments for Salmonella pathogenesis.
The specific aims are: 1) to determine the spatial and temporal organization of LRR effectors during S. typhimurium infection. 2) To isolate and identify host cell proteins that interacts with S. typhimurium LRR effectors. 3) To elucidate the contribution of LRR effectors in the pathogenesis of S. typhimurium.
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