Enteropathogenic Escherichia coli-induced myosin light chain phosphorylation alters intestinal epithelial permeability

Gastroenterology. 1997 Dec;113(6):1873-82. doi: 10.1016/s0016-5085(97)70006-4.


Background & aims: Infection of epithelial cells with enteropathogenic Escherichia coli (EPEC) induces phosphorylation of the 20-kilodalton myosin light chain (MLC20). The physiological consequence of this biochemical observation, however, has not been discerned. The aim of this study was to determine if EPEC-induced phosphorylation of MLC20 was involved in the associated perturbation of intestinal epithelial barrier function.

Methods: Cultured intestinal epithelial cells, T84, were infected with EPEC. The effects of protein kinase inhibitors on EPEC-induced perturbation of barrier function were assessed using electrophysiological techniques. Alterations in MLC20 phosphorylation were correlated with functional responses.

Results: Inhibition of myosin light chain kinase, but not protein kinase C or tyrosine kinase, prevented the decrease in resistance caused by EPEC infection and significantly diminished EPEC-induced MLC20 phosphorylation. Epithelial cell monolayers genetically manipulated to constitutively increase MLC20 phosphorylation were relatively resistant to the effects of EPEC on barrier function.

Conclusions: For the first time, these data show that a physiological consequence of the long-recognized increase in MLC20 phosphorylation by EPEC is perturbation of intestinal epithelial barrier function, which probably contributes to the diarrhea associated with this infection.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bacterial Adhesion / physiology
  • Cell Line
  • Electric Impedance
  • Enzyme Inhibitors / pharmacology
  • Escherichia coli / physiology*
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / physiology
  • Intestines / microbiology*
  • Myosin Light Chains / metabolism*
  • Myosin-Light-Chain Kinase / antagonists & inhibitors
  • Permeability
  • Phosphorylation
  • Protein Kinase C / antagonists & inhibitors
  • Protein-Tyrosine Kinases / antagonists & inhibitors


  • Enzyme Inhibitors
  • Myosin Light Chains
  • Protein-Tyrosine Kinases
  • Protein Kinase C
  • Myosin-Light-Chain Kinase