Ultrastrong <i>Staphylococcus aureus</i> adhesion to human skin: Calcium as a key regulator of noncovalent interactions.

Abstract

Calcium is a critical regulator of <i>Staphylococcus aureus</i> skin adhesion, stabilizing one of the strongest noncovalent biomolecular interactions ever recorded. Using in vitro and in silico single-molecule force spectroscopy, we demonstrate that calcium ions (Ca²⁺) are essential for the ultrastrong binding between the serine-aspartate repeat protein D (SdrD) adhesin and the human skin protein desmoglein-1 (DSG-1), withstanding forces exceeding 2 nanonewtons. Ca²⁺ ions stabilize both the SdrD complex and the mechanically robust SdrD B-domains, which exhibit unprecedented folding strength. In the context of atopic dermatitis (AD), disrupted calcium gradients amplify SdrD interactions, which could potentially intensify <i>S. aureus</i> virulence. Furthermore, abnormal DSG-1 distribution on AD-affected skin enhances bacterial adhesion. These findings provide crucial insights into the calcium-dependent regulation of bacterial adhesion and folding, suggesting possible therapeutic targets to combat <i>S. aureus</i> infections.