Intestinal barrier dysfunction by enteropathogenic Escherichia coli is mediated by two effector molecules and a bacterial surface protein.
The human intestinal pathogen, enteropathogenic Escherichia coli (EPEC), causes diarrhoeal disease by a mechanism that is dependent on the injection of effector proteins into the host cell. One effector, EspF, is reported to be required for EPEC to disrupt tight junction integrity of intestinal cells and increase the paracellular movement of molecules, which is likely to contribute to diarrhoea. Here, we show that not one but three EPEC-encoded factors play important roles in this process. Thus, the Map (Mitochondria-associated protein) effector is shown to: (i) be as essential as EspF for disrupting intestinal barrier function, (ii) be able to function independently of EspF, (iii) alter tight junction structure and (iv) mediate these effects in the absence of mitochondrial targeting. Additionally, the outer membrane protein Intimin is shown to be crucial for EspF and Map to disrupt the intestinal barrier function. This function of Intimin is completely independent of its interaction with its known receptor Tir, revealing a physiologically relevant requirement for Intimin interaction with alternative receptor(s). This work demonstrates that EPEC uses multiple multifunctional proteins to elicit specific responses in intestinal cells and that EPEC can control the activity of its injected effector molecules from its extracellular location.
Dean
Paul
P
Department of Pathology and Microbiology, Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK.
Kenny
Brendan
B
D018829:Adhesins, Bacterial / Q000378:metabolism; D018938:Caco-2 Cells; D002458:Cell Fractionation; D002462:Cell Membrane / Q000378:metabolism; D004926:Escherichia coli / Q000166:cytology / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000382:microbiology* / Q000503:physiopathology*; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D062793:Occludin; D011554:Pseudopodia / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D019108:Tight Junctions / Q000378:metabolism
D018829:Adhesins, Bacterial; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; C073819:eaeA protein, E coli