Enteropathogenic Escherichia coli activates ezrin, which participates in disruption of tight junction barrier function.
Enteropathogenic Escherichia coli (EPEC) is an important human intestinal pathogen, especially in infants. EPEC adherence to intestinal epithelial cells induces the accumulation of a number of cytoskeletal proteins beneath the bacteria, including the membrane-cytoskeleton linker ezrin. Evidence suggests that ezrin can participate in signal transduction. The aim of this study was to determine whether ezrin is activated following EPEC infection and if it is involved in the cross talk with host intestinal epithelial cells. We show here that following EPEC attachment to intestinal epithelial cells there was significant phosphorylation of ezrin, first on threonine and later on tyrosine residues. A significant increase in cytoskeleton-associated ezrin occurred following phosphorylation, suggesting activation of this molecule. Nonpathogenic E. coli and EPEC strains harboring mutations in type III secretion failed to elicit this response. Expression of dominant-negative ezrin significantly decreased the EPEC-elicited association of ezrin with the cytoskeleton and attenuated the disruption of intestinal epithelial tight junctions. These results suggest that ezrin is involved in transducing EPEC-initiated signals that ultimately affect host physiological functions.
Simonovic
I
I
Department of Medicine, Section of Digestive and Liver Diseases, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Arpin
M
M
Koutsouris
A
A
Falk-Krzesinski
H J
HJ
Hecht
G
G
D000818:Animals; D001422:Bacterial Adhesion; D002460:Cell Line; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction; D013912:Threonine / Q000378:metabolism; D019108:Tight Junctions / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism; D014774:Virulence; D000099149:Ezrin
D003598:Cytoskeletal Proteins; D010750:Phosphoproteins; D013912:Threonine; D014443:Tyrosine; D000099149:Ezrin