Calcium is a critical regulator of Staphylococcus aureus 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 intensi... More
Calcium is a critical regulator of Staphylococcus aureus 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 S. aureus 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 S. aureus infections.
