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

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 DtagO mutant was compared with the parental strain. Clearances of staphylococcus from the bloodstream were equivalent, but the DtagO 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 < .0001). 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.