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

Phillip A. Swanson, Amrita Kumar, Stanislav Samarin, Matam Vijay-Kumar, Kousik Kundu, Niren Murthy, Jason Hansen, Asma Nusrat, Andrew S. Neish

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

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 vivomodels ofwoundclosure. These results suggest that commensal bacteria regulate cell migration via induced generation of ROS in epithelial cells.

Original languageEnglish (US)
Pages (from-to)8803-8808
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number21
DOIs
StatePublished - May 24 2011

All Science Journal Classification (ASJC) codes

  • General

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