Enteropathogenic Escherichia coli induced alterations in epithelial barrier function

Enteropathogenic Escherichia coli (EPEC), a causative agent of infantile diarrhea, attaches to intestinal epithelial cells, subverts their function, and produces the characteristic "attaching and effacing (A/E) lesion". One mechanism by which EPEC causes diarrhea is by disrupting epithelial barrier function and elevating transcellular permeability. These result from an altered distribution of tight junction proteins such as occludin and claudin, as well as by the contraction of the peri-junctional actomyosin ring. While the signal transduction cascades leading to tight junction protein re-distribution remain to be elucidated, we have demonstrated that the contraction of the actomysin ring results from a calcium-dependent activation of myosin light chain kinase. EPEC pathogenesis requires a type III secretion system that directly injects effector proteins into host cells. One of the effector proteins, EspF, is critically required to cause barrier function alterations in a dose-dependent fashion. EspF has three proline-rich repeat sequences, and these have been predicted to interact with host proteins. Curiously, a clone deleted for these repeat sequences continued to complement an EspF deletion strain, suggesting that the proline-rich sequences are not critical for EspF-dependent barrier function alteration. The precise mechanism by which EspF induces barrier function alterations and the requirement of other secreted proteins for mediating this effect remain to be determined.