ERIN CRC: Molecular Basis of Nontyphoidal Salmonella Emergence

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DESCRIPTION (provided by applicant): Salmonella spp. cause a variety of human diseases, including nontyphoidal salmonellosis or NTS. NTS can present as a gastroenteritis, bacteremia, or a carriage state. Most NTS in the United States and developed nations occurs as a self-limited gastroenteritis, typically from contaminated food during specific outbreaks. In contrast, NTS in Africa is increasingly manifesting as a bacteremia without gastroenteritis, and shows human-to-human spread. Evidence suggests that this may be due in part to the immune status of the host populations, including comorbid infections such as HIV and malaria, and/or nutritional status. The goals of the ERIN CRC at the University of Washington will be to understand this difference in epidemiology by elucidating the contribution of microbial, host, and population factors in disease and carriage states. Three projects will be established to 1) examine host/pathogen diversity in clinical cases of NTS in Kenya (Judd Walson, Pl), 2) elucidate the genotypic and phenotypic correlates of pathogenicity in Salmonella strains from Africa and the United States (Sam Miller, PI) and 3) determine the immune correlates and mechanisms of limiting NTS bacteremia in the human host (Brad Cookson, PI). The projects will be coordinated through the efforts of an Administrative Core, which will also establish and manage a Pilot Project program.