The Role of EspH and Host Cell Proteins in Enteropathogenic Escherichia Coli-Induced Cell Death and Virulence

Abstract

Enteropathogenic 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 and harbors a type III secretion system (T3SS) that delivers virulence proteins directly into host epithelial cells. These proteins alter host structure and function, likely facilitating pathogenesis. We recently demonstrated that EspH, an EPEC secreted protein, is a critical virulence factor and that mutant strains lacking espH are impaired for pathogenesis. EspH induces host cell death through activation of caspases and mitochondrial fission. We hypothesizes that a wide range of host proteins are implicated in this cell death phenotype. Quantitation of host cell death during EPEC infection using siRNA-mediated knockdown of individual host cell proteins supports this hypothesis. A broad group of host protein knockdowns displayed altered host cell death during infection. The goal of my studies is to identify the host pathway(s) altered during EspH-induced epithelial cell death and, eventually, to establish the significance of this pathway in EPEC virulence.