Enteropathogenic Escherichia coli activates ezrin, which participates in disruption of tight junction barrier function

Enteropathogenic Escherichia coli (EPEC) is an important human intestinal p athogen, especially in infants. EPEC adherence to intestinal epithelial cel ls induces the accumulation of a number of cytoskeletal proteins beneath th e bacteria, including the membrane-cytoskeleton linker ezrin. Evidence sugg ests that ezrin can participate in signal transduction. The aim of this stu dy 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 lat er on tyrosine residues. A significant increase in cytoskeleton-associated ezrin occurred following phosphorylation, suggesting activation of this mol ecule. Nonpathogenic E. coli and EPEC strains harboring mutations in type I II secretion failed to elicit this response. Expression of dominant-negativ e ezrin significantly decreased the EPEC-elicited association of ezrin with the cytoskeleton and attenuated the disruption of intestinal epithelial ti ght junctions. These results suggest that ezrin is involved in transducing EPEC-initiated signals that ultimately affect host physiological functions.