Staphylococcus aureus vWF-binding protein triggers a strong interaction between clumping factor A and host vWF.

Area of Science:

• Microbiology
• Biophysics
• Molecular Biology

Background:

• Staphylococcus aureus uses cell wall-anchored adhesins like ClfA to bind host proteins.
• ClfA interacts with von Willebrand factor (vWF) through a secreted protein, vWF-binding protein (vWbp).
• The precise molecular mechanism and strength of this ternary complex interaction remain largely uncharacterized.

Purpose of the Study:

• To investigate the molecular mechanism of the ClfA-vWbp-vWF interaction using force spectroscopy on living bacteria.
• To quantify the binding forces within this ternary complex.
• To elucidate the structural basis for the observed binding strength.

Main Methods:

• Utilized atomic force microscopy (AFM) based single-molecule force spectroscopy.
• Performed experiments on living Staphylococcus aureus bacteria expressing ClfA.
• Analyzed the force-distance curves to determine rupture forces and binding kinetics.

Main Results:

• The ternary complex of ClfA, vWbp, and vWF exhibited exceptionally high binding forces, reaching up to 2000 pN.
• These forces significantly exceed those observed in other known adhesin-mediated ternary complexes.
• Evidence suggests a direct interaction between ClfA and vWF, potentially involving a 'dock, lock, and latch' mechanism, is crucial for the extreme tensile strength.

Conclusions:

• vWbp acts as an activator, enabling an ultra-strong, direct interaction between ClfA and vWF.
• This interaction is mediated by a previously undescribed mechanism contributing to bacterial adhesion.
• The identified ultra-strong interaction represents a promising target for developing novel anti-adhesion therapies, such as synthetic peptides.