Exploitation of host cells by enteropathogenic Escherichia coli.
Microbial pathogens have evolved many ingenious ways to infect their hosts and cause disease, including the subversion and exploitation of target host cells. One such subversive microbe is enteropathogenic Escherichia coli (EPEC). A major cause of infantile diarrhea in developing countries, EPEC poses a significant health threat to children worldwide. Central to EPEC-mediated disease is its colonization of the intestinal epithelium. After initial adherence, EPEC causes the localized effacement of microvilli and intimately attaches to the host cell surface, forming characteristic attaching and effacing (A/E) lesions. Considered the prototype for a family of A/E lesion-causing bacteria, recent in vitro studies of EPEC have revolutionized our understanding of how these pathogens infect their hosts and cause disease. Intimate attachment requires the type III-mediated secretion of bacterial proteins, several of which are translocated directly into the infected cell, including the bacteria's own receptor (Tir). Binding to this membrane-bound, pathogen-derived protein permits EPEC to intimately attach to mammalian cells. The translocated EPEC proteins also activate signaling pathways within the underlying cell, causing the reorganization of the host actin cytoskeleton and the formation of pedestal-like structures beneath the adherent bacteria. This review explores what is known about EPEC's subversion of mammalian cell functions and how this knowledge has provided novel insights into bacterial pathogenesis and microbe-host interactions. Future studies of A/E pathogens in animal models should provide further insights into how EPEC exploits not only epithelial cells but other host cells, including those of the immune system, to cause diarrheal disease.
Biotechnology Laboratory, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
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D000818:Animals; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000502:physiology; D003967:Diarrhea / Q000382:microbiology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000382:microbiology; D004927:Escherichia coli Infections / Q000382:microbiology; D019453:Escherichia coli O157 / Q000472:pathogenicity* / Q000502:physiology; D029968:Escherichia coli Proteins; D006801:Humans; D011956:Receptors, Cell Surface / Q000502:physiology; D015398:Signal Transduction; D014774:Virulence
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D011956:Receptors, Cell Surface; C109287:Tir protein, E coli