title: Enteric commensal bacteria potentiate epithelial restitution via reactive oxygen species-mediated inactivation of focal adhesion kinase phosphatases.
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.
authors.affiliation: Department of Pathology and Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Swanson
authors.forename: Amrita
authors.initials: A
authors.lastname: Kumar
authors.forename: Stanislav
authors.initials: S
authors.lastname: Samarin
authors.forename: Matam
authors.initials: M
authors.lastname: Vijay-Kumar
authors.forename: Kousik
authors.initials: K
authors.lastname: Kundu
authors.forename: Niren
authors.initials: N
authors.lastname: Murthy
authors.forename: Jason
authors.initials: J
authors.lastname: Hansen
authors.forename: Asma
authors.initials: A
authors.lastname: Nusrat
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Neish
mesh_terms: D000818:Animals; D002465:Cell Movement; D004755:Enterobacteriaceae / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010744:Phosphoric Monoester Hydrolases; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014945:Wound Healing
chemical_list: D017382:Reactive Oxygen Species; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse; D010744:Phosphoric Monoester Hydrolases