Enteric commensal bacteria potentiate epithelial restitution via reactive oxygen species-mediated inactivation of focal adhesion kinase phosphatases

Proc Natl Acad Sci U S A. 2011 May 24;108(21):8803-8. doi: 10.1073/pnas.1010042108. Epub 2011 May 9.

Abstract

The mechanisms by which enteric commensal microbiota influence maturation and repair of the epithelial barrier are relatively unknown. Epithelial restitution requires active cell migration, a process dependent on dynamic turnover of focal cell-matrix adhesions (FAs). Here, we demonstrate that natural, commensal bacteria stimulate generation of reactive oxygen species (ROS) in intestinal epithelia. Bacteria-mediated ROS generation induces oxidation of target cysteines in the redox-sensitive tyrosine phosphatases, LMW-PTP and SHP-2, which in turn results in increased phosphorylation of focal adhesion kinase (FAK), a key protein regulating the turnover of FAs. Accordingly, phosphorylation of FAK substrate proteins, focal adhesion formation, and cell migration are all significantly enhanced by bacterial contact in both in vitro and in vivo models of wound closure. These results suggest that commensal bacteria regulate cell migration via induced generation of ROS in epithelial cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Movement
  • Enterobacteriaceae / metabolism*
  • Epithelial Cells / metabolism*
  • Focal Adhesion Kinase 1 / metabolism*
  • Focal Adhesions / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Phosphoric Monoester Hydrolases
  • Reactive Oxygen Species / metabolism*
  • Wound Healing

Substances

  • Reactive Oxygen Species
  • Focal Adhesion Kinase 1
  • Ptk2 protein, mouse
  • Phosphoric Monoester Hydrolases