PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
EmbargoRelease after 30-Dec-2020
AbstractEnteropathogenic Escherichia coli (EPEC) is a leading cause of infantile diarrhea, particularly in developing countries. EPEC belongs to the attaching and effacing (A/E) family of pathogens. All A/E pathogens harbor a type III secretion system (T3SS) that delivers virulence proteins directly into host epithelial cells. These proteins mediate diverse structural and functional alterations that likely facilitate pathogenesis. We recently demonstrated that EspZ, a secreted protein unique to A/E pathogens, is a critical virulence factor and that mutant strains lacking espZ are impaired for pathogenesis in both mouse and rabbit models of infection. EspZ prevents premature death of cultured intestinal epithelial cells by inhibiting intrinsic apoptosis. We hypothesized that EspZ promotes cell survival by engaging host proteins. Yeast two-hybrid studies identified the mitochondrial fission protein, hFis1, as a putative EspZ interactor. Co-immunoprecipitation studies confirmed EspZ-hFis1 interaction, and hFis1 was shown to be re-distributed in infected cells. These observations are consistent with the established role of hFis1 in intestinal cell survival pathways. The goal of my studies is to validate hFis1-EspZ interactions in epithelial cell cyto-protection and, eventually, to establish the significance of this pathway in EPEC virulence.
Degree ProgramGraduate College