title: Regulation of epidermal tight-junctions (TJ) during infection with exfoliative toxin-negative Staphylococcus strains.
abstract: Tight Junction (TJ) proteins have been shown to exert a barrier function within the skin. Here, we study the fate of TJ proteins during the challenge of the skin by bacterial colonization and infection. We investigated the influence of various exfoliative toxin-negative Staphylococcus strains on TJ, adherens junction (AJ), desmosomal proteins, and actin in a human keratinocyte infection culture and in a porcine skin infection model. We found that the pathogen Staphylococcus aureus downregulates TJ and subsequently AJ and desmosomal proteins, including atypical protein kinase C, an essential player in TJ formation, at the cell-cell borders of keratinocytes in a time and concentration dependent manner. Little changes in protein and RNA levels were seen, indicating redistribution of proteins. In cultured keratinocytes, a reduction of transepithelial resistance was observed. Staphylococcus epidermidis shows only minor effects. All strains induced enhanced expression of occludin and ZO-1 at the beginning of colonization/infection. Thus, we demonstrate that TJ are likely to be involved in skin infection of exfoliative toxin-negative S. aureus. As we did not find a change in actin, and as changes of TJ preceded alterations of AJs and desmosomes, we suggest that S. aureus targets TJ.
authors.affiliation: Department of Dermatology and Venerology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Ohnemus
authors.forename: Klaas
authors.initials: K
authors.lastname: Kohrmeyer
authors.forename: Pia
authors.initials: P
authors.lastname: Houdek
authors.forename: Holger
authors.initials: H
authors.lastname: Rohde
authors.forename: Ewa
authors.initials: E
authors.lastname: Wladykowski
authors.forename: Sabine
authors.initials: S
authors.lastname: Vidal
authors.forename: Matthias A
authors.initials: MA
authors.lastname: Horstkotte
authors.forename: Martin
authors.initials: M
authors.lastname: Aepfelbacher
authors.forename: Nina
authors.initials: N
authors.lastname: Kirschner
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Behne
authors.forename: Ingrid
authors.initials: I
authors.lastname: Moll
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Brandner
mesh_terms: D000199:Actins / Q000378:metabolism; D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D003896:Desmosomes / Q000378:metabolism; D004195:Disease Models, Animal; D004817:Epidermis / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism*; D062793:Occludin; D010750:Phosphoproteins / Q000378:metabolism; D013203:Staphylococcal Infections / Q000378:metabolism* / Q000382:microbiology; D013211:Staphylococcus aureus; D013212:Staphylococcus epidermidis; D019108:Tight Junctions / Q000737:chemistry / Q000378:metabolism / Q000382:microbiology*; D062826:Zonula Occludens-1 Protein
chemical_list: D000199:Actins; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein