Bacterial pathogens under high-tension: Staphylococcus aureus adhesion to von Willebrand factor is activated by force

Abstract

Attachment of Staphylococcus aureus to platelets and endothelial cells involves binding of bacterial cell sur-face protein A (SpA) to the large plasma glycoprotein von Willebrand factor (vWF). SpA-mediated bacterial adhesion to vWF is controlled by fluid shear stress, yet little is currently known about the underlying molecu-lar mechanism. In a recent publication, we showed that the SpA-vWF interaction is tightly regulated by mechanical force. By means of single-molecule pulling experiments, we found that the SpA-vWF bond is ex-tremely strong, being able to resist forces which large-ly outperform the strength of typical receptor-ligand bonds. In line with flow experiments, strong adhesion is activated by mechanical tension. These results sug-gest that force induces conformational changes in the vWF molecule, from a globular to an extended state, leading to the exposure of cryptic binding sites to which SpA strongly binds. This force-sensitive mecha-nism may largely contribute to help S. aureus bacteria to resist shear stress of flowing blood during infection.