title: Lack of wall teichoic acids in Staphylococcus aureus leads to reduced interactions with endothelial cells and to attenuated virulence in a rabbit model of endocarditis.
abstract: Wall teichoic acids (WTAs) are major surface components of gram-positive bacteria that have recently been shown to play a key role in nasal colonization by Staphylococcus aureus. In the present study, we assessed the impact that WTAs have on endovascular infections by using a WTA-deficient S. aureus mutant ( Delta tagO). There were no significant differences detected between the isogenic parental strain (SA113) and the Delta tagO mutant in polymorphonuclear leukocyte-mediated opsonophagocytosis; killing by a prototypic platelet microbicidal protein; or binding to platelets, fibronectin, or fibrinogen. However, compared with the parental strain, the Delta tagO mutant adhered considerably less well to human endothelial cells, especially under flow conditions (70.3% reduction; P<.05). Beads coated with WTA bound to endothelium in a dose-dependent manner, suggesting that WTA contributes specifically to this interaction. These in vitro data closely paralleled those from a rabbit model of infective endocarditis in which the Delta tagO mutant was compared with the parental strain. Clearances of staphylococcus from the bloodstream were equivalent, but the Delta tagO mutant showed a significantly reduced capacity to both colonize sterile cardiac vegetations (P<.05) and proliferate within these vegetations, the kidneys, and the spleen (P<.001). We conclude that WTA is an important factor in the induction and progression of endovascular S. aureus infection, likely through a specific interaction with endothelial cells.
authors.affiliation: Cellular and Molecular Microbiology Division, Medical Microbiology and Hygiene Department, University of Tübingen, 72076 Tübingen, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Weidenmaier
authors.forename: Andreas
authors.initials: A
authors.lastname: Peschel
authors.forename: Yan-Qiong
authors.initials: YQ
authors.lastname: Xiong
authors.forename: Sascha A
authors.initials: SA
authors.lastname: Kristian
authors.forename: Klaus
authors.initials: K
authors.lastname: Dietz
authors.forename: Michael R
authors.initials: MR
authors.lastname: Yeaman
authors.forename: Arnold S
authors.initials: AS
authors.lastname: Bayer
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002473:Cell Wall / Q000378:metabolism; D004697:Endocarditis, Bacterial / Q000382:microbiology*; D042783:Endothelial Cells / Q000502:physiology*; D006801:Humans; D009154:Mutation; D009504:Neutrophils; D010587:Phagocytosis; D011817:Rabbits; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000235:genetics / Q000472:pathogenicity*; D013682:Teichoic Acids / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: D013682:Teichoic Acids