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

PA Swanson, A Kumar, S Samarin… - Proceedings of the …, 2011 - National Acad Sciences
Proceedings of the National Academy of Sciences, 2011National Acad Sciences
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 …
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.
National Acad Sciences