Staphylococcus aureus is an opportunistic pathogen. In response to changing host environments, this bacterium has the capability to switch on selective sets of genes to enhance its chances for survival. This switching process is precisely controlled by global regulatory elements. There are two major groups of global regulatory elements in S. aureus, including two-component regulatory systems (TCRSs) and the SarA protein family. Presumably, the sensor proteins of the 16 TCRSs in S. aureus provide external sensing, while the response regulators, in conjunction with alternative transcription factors and the SarA protein family, function as effectors within the intricate regulatory network to respond to environmental stimuli. Sequence alignment and structural data indicate that the SarA protein family could be subdivided into three subfamilies: (1) single-domain proteins; (2) double-domain proteins; and (3) proteins homologous to the MarR protein family. Recent data using reporter gene fusions in animal models, have confirmed distinct expression profiles of selected regulatory and target genes in vitro vs. in vivo.

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 (DtagO). There were no significant differences detected between the isogenic parental strain (SA113) and the DtagO 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 DtagO mutant adhered considerably less well to human endothelial cells, especially under flow conditions (70.3% reduction;). Beads coated with WTA bound to endothelium in a dose-dependent manner, P ! .05 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 ( ) and proliferate within these P ! .05 vegetations, the kidneys, and the spleen ( ). We conclude that WTA is an important factor in the P ! .001 induction and progression of endovascular S. aureus infection, likely through a specific interaction with endothelial cells.An important feature of Staphylococcus aureus bacteremia is the high frequency with which the organism spreads from the bloodstream to other targets, such as