Host Innate Immune Factors Influencing Enterohemorrhagic Escherichia coli Pathogenicity

Abstract

Enterohemorrhagic Escherichia coli (EHEC) is a significant foodborne attaching and effacing (A/E) pathogen that causes diarrhea, hemorrhagic colitis and the hemolytic-uremic syndrome (HUS) in humans. EHEC is closely related to enteropathogenic E. coli (EPEC) and both induce characteristic A/E lesions on the gut mucosal surface. During EHEC and EPEC infection, host innate immune responses, such as inflammation and cell death are rapidly activated, upon the detection of bacterial components and virulence factor activity. To promote A/E lesion formation and dissemination of the pathogen in the body, EHEC and EPEC deliver a repertoire of effector proteins, including Tir, NleA/EspI and NleB to -H, to the host cell cytosol via a type III secretion system (T3SS). These interfere with a range of host cell processes, including host defense mechanisms. Several T3SS effector proteins specifically modify or cleave host proteins involved in inflammation and cell death, thereby inactivating these pathways. The identification of the host targets and the characterization of the biochemical function of T3SS effectors have greatly contributed to understanding the pathogenesis of EHEC and EPEC infections.