Potential roles of salicylic acid (SAL) in the pathogenesis of S. aureus endovascular infection. (I) SAL pretreatment of S. aureus results in overexpression of SigB-dependent genes in both an rsbU-positive and an rsbU-negative background, suggesting SigB activation independent of the anti–ς-factor RsbU. (II) Activation of the sarAP3 promotor appears to contribute to decreased expression of active SarA protein, putatively via inhibitory activity of the sarAP3 gene product. Again, SAL appears to contribute to SarA reduction in a sarAP3-additive fashion. (III) As SarA controls expression of RNAII and RNAIII, the net effect of SAL is a mitigation of the agr response. Since α-toxin (hla) expression depends on both sar and agr, and expression of wall-bound adhesins is also in part controlled by sar, the mitigation of both adhesin and toxin expression in SAL-treated microorganisms appears to depend on a combined sar/agr effect; yet other regulators may also be involved. (IV) In addition to hla, the expression of other secreted molecules such as the extracellular adhesive protein Eap depends on agr and sarA and may be downregulated under the influence of SAL. Expression of the polysaccharide intracellular adhesin (PIA) is suggested to depend on sigB, which may positively control expression of icaADBC, with consequences not yet fully understood in S. aureus endovascular infection. The S. aureus adhesins (FnBPA, FnBPB, ClfA, and ClfB) recognize fibronectin and fibrinogen, which are presented on ECs and platelets.