Ultrastrong Staphylococcus aureus adhesion to human skin: Calcium as a key regulator of noncovalent interactions
- Constance Chantraine
- Priscila S. F. C. Gomes
- Marion Mathelié-Guinlet
- Diego E. B. Gomes
- Zhiyong Zheng
- Julianne Clowry
- Mary B. Turley
- Alan D. Irvine
- Joan A. Geoghegan
- Rafael C. Bernardi
- Yves F. Dufrêne
2025-09-03
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 (Ca 2+ ) 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. Ca 2+ 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.