Nanomechanics of the molecular complex between staphylococcal adhesin SpsD and elastin.

Abstract

Staphylococcus pseudintermedius surface protein SpsD binds to extracellular matrix proteins to invade canine epithelial cells. Using single-molecule experiments, we show that SpsD engages in two modes of interaction with elastin that are tightly controlled by physical stress. Binding is weak (∼100 pN) at low tensile force (i.e. loading rate), but is dramatically enhanced (up to ∼1500 pN) by mechanical tension. Consistent with a "dock, lock, and latch" (DLL) mechanism, this force represents among the highest mechanical strengths known for a non-covalent biological interaction. The transition from weak to strong binding correlates with an increase in molecular stiffness but, surprisingly, with a decrease in molecular extension. This unanticipated mechanical behavior indicates that the adhesin is engaged in two distinct interaction mechanisms. Our results emphasize the crucial role of protein nanomechanics in the adhesion of staphylococci, and illustrate their wide diversity of force-dependent ligand-binding activities. These single-molecule mechanical experiments may contribute to the development of antiadhesion approaches to treat infections caused by S. pseudintermedius and other bacterial pathogens engaged in DLL interactions.