Definition of targets to inhibit Salmonella colonization of the intestine
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Salmonella cause an estimated 1.4 million cases of foodborne disease, resulting in ~13,000 hospitalizations, and >500 deaths annually in the United States. There are currently no treatments for uncomplicated Salmonella infections, or interventions to block persistent fecal shedding of this organism from livestock. The goal of this proposal is to understand how Salmonella, a common agent of bacterial foodborne disease in humans, can survive and grow in the intestine during infection. Our hypothesis is that Salmonella encodes proteins that allow it to grow in the intestine in oxygen-limited conditions, and we do not yet know the functions of many of these proteins. We have discovered 16 genes that appear to be important for Salmonella growth in the intestine and the goal of this project is to identify the functions of several of the products of these genes. The objectives of this project are to (1) measure the survival and growth of strains lacking these genes both in the intestine and in oxygen limited conditions in the laboratory, (2) to identify which of these genes participate in virulence pathways that are already known, (3) to identify the functions of products of selected genes, and (4) to model the structure and potential substrates of selected candidate gene products. This knowledge can be used in the future to develop new vaccines and drugs to prevent and treat Salmonella infections in humans and livestock.