Adherence properties of Staphylococcus aureus under static and flow conditions: Roles of agr and sar loci, platelets, and plasma ligands

Global regulatory genes in Staphylococcus aureus, including agr and sar, ar e known to regulate the expression of multiple virulence factors, including cell wall adhesins, In the present study, the adherence of S. aureus RN639 0 (wild type), RN6911 (agr), ALC136 (sar), and ALC135 (agr sar) to immobili zed fibrinogen, fibronectin, von Willebrand factor (vWF), extracellular mat rix (ECM), and human endothelial cells (EC) EAhy.926 was studied. Bacteria grown to postexponential phase were subjected to light oscillation (static condition) or to shear stress at 200 s(-1) (flow condition) on tissue cultu re polystyrene plates coated with either protein ligands, ECM, or EC, Adher ence of nonlabeled bacteria to immobilized ligands was measured by an image analysis system, while adherence of [H-3]thymidine-labeled S, aureus to EC M and EC was measured by a p-scintillation counter. The results showed incr eased adherence of agr and agr sar mutants to immobilized fibrinogen and hi gher potential of these mutants to induce platelet aggregation in suspensio n, decreased adherence of sar and agr sar mutants to immobilized fibronecti n and VWF as well as to ECM and EC, increased adherence of both S. aureus w ild type and sar mutant to EC treated with platelet-rich plasma (PRP) compa red to platelet-poor plasma (PPP) and to EC treated with PPP compared to th e control, and increased adherence of S. aureus wild type to EC coated with PRP in which platelets were activated with phorbol 12-myristate 13-acetate compared to intact PRP, This finding paralleled the increased adherence to EC of activated compared to intact platelets. It is suggested that platele t-mediated S. aureus adherence to EC depends on platelet activation and the number of adherent platelets and available receptors on the platelet membr ane. In conclusion, the agr locus downregulates S. aureus adherence to fibr inogen, while the sar locus upregulates S, aureus adherence to fibronectin, vWF, ECM, and EC, The effect of both agr and sar on S, aureus adherence pr operties develops primarily under flow conditions, which suggests different adhesion mechanisms in static and flow conditions.