Grant: Operating Grant

Enteropathogenic E. coli (EPEC) is a leading cause of bacterial diarrhea, causing much morbidity and mortality in children worldwide. Enterohemorrhagic E. coli (EHEC; E. coli O157) is a close relative of EPEC that causes "hamburger disease" and hemolytic uremic syndrome (HUS). EHEC was the source of the Walkerton, Ont. outbreak and the XL Foods beef recall. EPEC and EHEC belong to a family of attaching and effacing pathogens that adhere to intestinal epithelial cells, causing a specialized disruption on the intestinal cell surface that mediates disease. This application addresses several fundamental questions pertaining to secreted pathogenic E. coli proteins that are injected into intestinal cells and are needed to cause disease. This includes studying how the injection machinery (called a type III secretion system) is assembled and functions. It also includes studying how the injected proteins function inside mammalian cells and how they modulate host signaling pathways. Their contribution to disease will be studied in a relevant animal disease model. Collectively, these studies will provide important information about disease progression and the role of secreted virulence factors, which can be applied to design therapeutics and vaccines against diseases caused by these important foodborne pathogens.