title: Putting on the brakes: Bacterial impediment of wound healing.
abstract: The epithelium provides a crucial barrier to infection, and its integrity requires efficient wound healing. Bacterial cells and secretomes from a subset of tested species of bacteria inhibited human and porcine corneal epithelial cell migration in vitro and ex vivo. Secretomes from 95% of Serratia marcescens, 71% of Pseudomonas aeruginosa, 29% of Staphylococcus aureus strains, and other bacterial species inhibited epithelial cell migration. Migration of human foreskin fibroblasts was also inhibited by S. marcescens secretomes indicating that the effect is not cornea specific. Transposon mutagenesis implicated lipopolysaccharide (LPS) core biosynthetic genes as being required to inhibit corneal epithelial cell migration. LPS depletion of S. marcescens secretomes with polymyxin B agarose rendered secretomes unable to inhibit epithelial cell migration. Purified LPS from S. marcescens, but not from Escherichia coli or S. marcescens strains with mutations in the waaG and waaC genes, inhibited epithelial cell migration in vitro and wound healing ex vivo. Together these data suggest that S. marcescens LPS is sufficient for inhibition of epithelial wound healing. This study presents a novel host-pathogen interaction with implications for infections where bacteria impact wound healing and provides evidence that secreted LPS is a key factor in the inhibitory mechanism.
authors.affiliation: The Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Eye Center, Ophthalmology and Visual Sciences Research Center, Department of Ophthalmology (OVSRC), University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Brothers
authors.affiliation: The Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Eye Center, Ophthalmology and Visual Sciences Research Center, Department of Ophthalmology (OVSRC), University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Stella
authors.affiliation: The Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Eye Center, Ophthalmology and Visual Sciences Research Center, Department of Ophthalmology (OVSRC), University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Hunt
authors.affiliation: The Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Eye Center, Ophthalmology and Visual Sciences Research Center, Department of Ophthalmology (OVSRC), University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Romanowski
authors.affiliation: Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Liu
authors.affiliation: The Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Eye Center, Ophthalmology and Visual Sciences Research Center, Department of Ophthalmology (OVSRC), University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Jes K
authors.initials: JK
authors.lastname: Klarlund
authors.affiliation: The Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Eye Center, Ophthalmology and Visual Sciences Research Center, Department of Ophthalmology (OVSRC), University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Robert M Q
authors.initials: RM
authors.lastname: Shanks
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D019573:Epithelium, Corneal / Q000166:cytology / Q000473:pathology; D006801:Humans; D008070:Lipopolysaccharides / Q000096:biosynthesis / Q000633:toxicity; D008856:Microscopy, Fluorescence; D009154:Mutation; D011112:Polymyxin B / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D012706:Serratia marcescens / Q000187:drug effects / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000378:metabolism*; D013552:Swine; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D001426:Bacterial Proteins; D017077:Culture Media, Conditioned; D008070:Lipopolysaccharides; D011112:Polymyxin B