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Author Notes:

To whom correspondence should be addressed. E-mail: aneish@emory.edu.

Edited by Ralph R. Isberg, Tufts University School of Medicine, Boston, MA, and approved April 15, 2011 (received for review July 14, 2010)

Author contributions: P.A.S., A.K., S.S., M.V.-K., and A.S.N. designed research; P.A.S., A.K., S.S., and M.V.-K. performed research; P.A.S., A.K., K.K., N.M., J.H., and A.N. contributed new reagents/analytic tools; P.A.S., A.K., S.S., M.V.-K., J.H., and A.S.N. analyzed data; and P.A.S., A.K., A.N., and A.S.N. wrote the paper.

P.S. and A.K. contributed equally to this work.

Subjects:

Research Funding:

This work was supported by Grants DK071604 and AI064462 from the National Institutes of Health (to A.S.N.) and the Emory Digestive Diseases Research Development Center Core Grant (DK 0644399).

Keywords:

  • intestine
  • gastroenterology
  • phosphoprotein phosphatases
  • probiotics
  • lactobacillus

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

Tools:

Journal Title:

Proceedings of the National Academy of Sciences

Volume:

Volume 108, Number 21

Publisher:

, Pages 8803-8808

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

Beginning with articles submitted in Volume 106 (2009) the author(s) retains copyright to individual articles, and the National Academy of Sciences of the United States of America retains an exclusive license to publish these articles and holds copyright to the collective work.

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