Co-operative behaviour of the effector proteins of enteropathogenic E. coli (EPEC) in inducing disease-related changes in cell physiology
Enteropathogenic E.coli (EPEC) infection is linked to millions of diarrhoeal cases and several hundred infant deaths each year. An unusual feature of EPEC infection is that it does not induce strong inflammatory responses. In the 1970’s histopathological examination of infected tissue linked this disease to the binding of bacteria to small intestinal enterocytes, loss of absorptive microvilli and the formation of actin-rich pedestal-like structures beneath the adherent bacteria. However, although the capacity of EPEC to disrupt the epithelial barrier could provide a mechanism for the diarrhoea, the kinetics of epithelial disruption are too slow to explain the rapid onset of symptoms. Our previous work provided major insights into understanding how EPEC alters the cellular physiology of the host, binds to epithelia and induces pedestal formation. Recent breakthroughs have stemmed from our finding that injected effector proteins can target multiple compartments and function together in redundant, synergistic as well as antagonistic fashions (in different effector combinations) to trigger cellular changes associated with disease. Importantly, the work not only identified sets of effectors responsible for the disruption of epithelial barrier function and the loss of microvilli, it also provided plausible mechanisms for the rapid onset of diarrhoea and the non-inflammatory nature of the disease.
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Dean P, Maresca M, Schüller S, Phillips A and Kenny B. 2006. Intestinal microvilli effaced by action of three enteropathogenic E. coli-injected effector proteins. Proc. Natl. Acad Sci, USA 103, 1876-1881.
Ruchaud-Sparagano M-H., Maresca M and Kenny B. 2007. Enteropathogenic E. coli (EPEC) inactivate innate-immune responses prior to compromising epithelial barrier function. Cellular Microbiology (In press).
