Staphylococcus aureus clumping factor A is a force-sensitive molecular switch that activates bacterial adhesion

Area of Science:

• Microbiology
• Biophysics
• Biomaterials Science

Background:

• Clumping factor A (ClfA) from *Staphylococcus aureus* is a key virulence factor.
• ClfA mediates bacterial adhesion to fibrinogen (Fg), crucial for biomaterial colonization.
• The molecular forces governing ClfA-Fg interaction, especially under shear stress, remain poorly understood.

Purpose of the Study:

• To investigate the strength and dynamics of the ClfA-Fg interaction under varying mechanical forces.
• To elucidate the molecular mechanisms behind *S. aureus* adhesion to Fg under high shear stress.
• To understand how ClfA facilitates bacterial colonization of protein-coated biomaterials.

Main Methods:

• Single-molecule force spectroscopy experiments were employed.
• The ClfA-Fg bond strength was measured at different tensile forces.
• Inhibition studies using a peptide mimicking the Fg γ-chain C-terminal segment were performed.

Main Results:

• ClfA-Fg interaction exhibits catch-bond behavior, significantly strengthening under mechanical tension (0.1 nN to 1.5 nN).
• The enhanced bond strength is dependent on specific binding sites within the ClfA-Fg complex.
• A peptide mimicking the Fg γ-chain C-terminal segment inhibited the strong, tension-dependent bonds.

Conclusions:

• ClfA functions as a force-sensitive molecular switch, potentiating *S. aureus* adhesion under mechanical stress.
• A two-site binding model regulated by mechanical tension explains the force-activated adhesion mechanism.
• This mechanism is critical for understanding *S. aureus* colonization of medical devices under physiological shear stress.