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PNAS 108 (21): 8803-8808

Copyright © 2011 by the National Academy of Sciences.

BIOLOGICAL SCIENCES / MEDICAL SCIENCES

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

Phillip A. Swanson, IIa,1, Amrita Kumara,1, Stanislav Samarina, Matam Vijay-Kumara, Kousik Kundub, Niren Murthyb, Jason Hansenc, Asma Nusrata, and Andrew S. Neisha,2

Departments of aPathology and cPediatrics, Emory University School of Medicine, Atlanta, GA 30322; and bDepartment of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332

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

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.

Key Words: intestine • gastroenterology • phosphoprotein phosphatases • probiotics • lactobacillus

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.

1P.S. and A.K. contributed equally to this work.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1010042108/-/DCSupplemental.

2To whom correspondence should be addressed. E-mail: aneish{at}emory.edu.

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