Staphylococcus aureus binds to the N-terminal region of corneodesmosin to adhere to the stratum corneum in atopic dermatitis

Significance Staphylococcus aureus colonizes skin of patients with atopic dermatitis (AD), increasing disease severity. Colonization involves bacterial adhesion to skin corneocytes, and elucidating the molecular basis of interactions governing adhesion is crucial to further our understanding of pathogenesis and inform targeted therapies. We identify host and pathogen factors that enable adhesion. We demonstrate that S. aureus interacts with the N-terminal region of corneodesmosin on the surface of patient corneocytes. This interaction is mediated by two bacterial cell wall-anchored proteins (fibronectin binding protein B and clumping factor B). Frequency and force of bacterial binding to AD corneocytes decreased when the N-terminal region of corneodesmosin was blocked with an antibody, indicating the contribution of this interaction during S. aureus adhesion to human skin.