title: Staphylococcus aureus hemolysin A disrupts cell-matrix adhesions in human airway epithelial cells.
abstract: Treatment of primary or immortalized human airway epithelial cells (16HBE14o-, S9) or alveolar cancer cells (A549) with recombinant hemolysin A (rHla), a major virulence-associated factor of Staphylococcus aureus, induces alterations in cell shape and formation of paracellular gaps in the cell layer. Semiquantitative Western blotting using extracts of freshly isolated airway tissue (nasal epithelium) or 16HBE14o- model cells revealed that phosphorylation levels of focal adhesion kinase (Fak) and paxillin were altered upon treatment of tissue or cells with rHla. Immune fluorescence analyses showed that rHla treatment of 16HBE14o- cells results in losses of vinculin and paxillin from focal contacts and a net reduction in the number of focal contacts. The actin cytoskeleton was strongly remodeled. We concluded that treatment of cells with rHla activates Fak signaling, which accelerates focal contact turnover and prevents newly formed focal contacts (focal complexes) from maturation to focal adhesions. The inability of rHla-treated cells to form stable focal adhesions may be one factor that contributes to gap formation in the cell layer. In vivo, such changes may disturb the defensive barrier function of the airway epithelium and may facilitate lung infections by S. aureus.
authors.affiliation: 1 Animal Physiology and Biochemistry, Zoological Institute, Ernst Moritz Arndt-University, Greifswald, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Hermann
authors.forename: Susann
authors.initials: S
authors.lastname: Räth
authors.forename: Sabine
authors.initials: S
authors.lastname: Ziesemer
authors.forename: Thomas
authors.initials: T
authors.lastname: Volksdorf
authors.forename: Regine J
authors.initials: RJ
authors.lastname: Dress
authors.forename: Melanie
authors.initials: M
authors.lastname: Gutjahr
authors.forename: Christian
authors.initials: C
authors.lastname: Müller
authors.forename: Achim G
authors.initials: AG
authors.lastname: Beule
authors.forename: Jan-Peter
authors.initials: JP
authors.lastname: Hildebrandt
mesh_terms: D001427:Bacterial Toxins / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism*; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006460:Hemolysin Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D051419:Paxillin / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000235:genetics; D011023:Pneumonia, Staphylococcal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism*; D016596:Vinculin / Q000235:genetics / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D006460:Hemolysin Proteins; C496061:PXN protein, human; D051419:Paxillin; C488955:VCL protein, human; C021091:staphylococcal alpha-toxin; D016596:Vinculin; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human
keywords: Staphylococcus aureus; epithelial barrier function; focal adhesions; hemolysin A; human airway epithelial cells