Attaching effacing Escherichia coli and paradigms of Tir-triggered actin polymerization: getting off the pedestal.
Enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC and EHEC) colonize the gut mucosa via attaching and effacing (A/E) lesions. For years cultured cells were used as model systems to study A/E lesion formation, which showed actin accumulation under attached bacteria that can be raised above the plasma membrane in a pedestal-shaped structure. Studies of prototypical strains revealed that although both converge on N-WASP EPEC and EHEC O157:H7 use different actin polymerization pathways. While EPEC use the Tir-Nck pathway, Tir(EHECO157) cooperates with TccP/EspF(U) to activate N-WASP. However, recent in vitro studies revealed a common EPEC and EHEC Tir-dependent and Nck-independent inefficient actin polymerization pathway. Unexpectedly, bacterial populations studies demonstrated that most non-O157 EHEC strains and EPEC lineage 2 strains can utilize both the Nck and TccP2 pathways in vitro. Importantly, in vivo and ex vivo mucosal infections have shown efficient A/E lesion formation independently of Nck and TccP. This review covers the progression in our understanding of EPEC and EHEC infection, through the different milestones obtained using cultured cells, to the realization that EPEC and EHEC have much more in common than previously appreciated and that mucosal attachment and microvillous effacement may be the key events, rather than pedestal formation.
Division of Cell and Molecular Biology, Imperial College London, London, UK. g.frankel@imperial.ac.uk
Gad
G
Frankel
Alan D
AD
Phillips
D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D001422:Bacterial Adhesion; D002352:Carrier Proteins / Q000378:metabolism; D054324:Enterohemorrhagic Escherichia coli / Q000502:physiology*; D054308:Enteropathogenic Escherichia coli / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D015513:Oncogene Proteins / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000378:metabolism
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; C078332:Nck protein; D015513:Oncogene Proteins; D011956:Receptors, Cell Surface; C526042:TccP2 protein, E coli; C109287:Tir protein, E coli; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal