UBC Theses and Dissertations
Novel overlapping roles of Salmonella pathogenicity islands 1 and 2 in intestinal salmonellosis Coburn, Bryan
Non-typhoidal Salmonella species are a significant cause of human diarrheal disease, incurring worldwide morbidity and mortality. The prevailing dogma arising from animal models of Salmonella enteropathogenesis is that the virulence associated genomic regions, Salmonella pathogenicity island (SPI) -1 and SPI-2, are essential for intracellular invasion/intestinal disease and intracellular survival/systemic disease, respectively. This paradigm partly reflects limitations of animal models currently used to study in vivo pathogenesis! In this thesis, a new model of murine Salmonella enteropathogenesis is presented which allows a novel examination of this theoretical dichotomy. Using this model, SPI-2 was shown to be required for complete enteropathogenesis in Salmonella enterica serovar Typhimurium infection. In addition, murine and bovine intestinal inflammation was identified in the absence of SPI-1, previously thought to be essential for intestinal disease. These findings are corroborated in human disease by the identification of a SPI-1 deficient human clinical diarrheal Salmonella enterica isolate. These strains were isolated from patients affected with severe diarrheal disease in Shenzhen, China. These are the first findings that demonstrate that SPI-2 is required for intestinal pathogenesis early in murine infection, and that SPI-1 is dispensible for enteropathogenesis in animal and human infections with S. enterica. These observations indicate that disease models, diagnostic and therapeutic approaches predicated on the requirement for SPI-1 in intestinal disease do not accurately describe intestinal salmonellosis.
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