Background:Staphylococcus aureus colonizes the skin lesions of more than 90% of patients with atopic dermatitis (AD). The mechanism for increased S aureus colonization in AD is unknown. However, the initial event in colonization requires adherence of S aureus to the skin. Objective: The purpose of this study was to examine the roles of various bacterial adhesins on S aureus binding to AD skin. Methods: In an attempt to delineate the mechanism behind this adherence process, an in vitro bacterial binding assay was developed to quantitate the adherence of various S aureus strains to AD, psoriatic, and normal skin sections. S aureus strains used in this study were obtained either from cultures of AD skin lesions or from genetically manipulated strains of S aureus that lacked specific microbial surface components recognizing adhesive matrix molecules (MSCRAMMs)—namely, fibronectin-binding protein (Fnbp), fibrinogen-binding protein (Clf), collagen-binding protein (Cna), and their parent strains. In addition, S aureus strains from patients with AD were pretreated with fibronectin or fibrinogen to block MSCRAMM receptors and interfere with binding. Results: Under all experimental conditions, binding of S aureus was localized primarily to the stratum corneum. Immunocytochemical staining of AD skin sections showed a redistribution of fibronectin to the cornified layer, an observation not seen in normal skin. S aureus binding to uninvolved AD skin was significantly greater than the binding to uninvolved psoriatic skin (P < .0001) and normal skin (P < .0005). The Fnbp-negative S aureus showed a significant reduction in binding to the AD skin (P < .0001) but not to the psoriatic and normal skin. In the AD skin, a significant reduction in the binding of S aureus was also observed in the Clf-negative strain (P < .0001) but not in the Cna-negative S aureus . Preincubation of S aureus with either fibronectin or fibrinogen also inhibited bacterial binding to AD skin (P < .0001). Conclusion: These data suggest that fibronectin and fibrinogen—but not collagen—play a major role in the enhanced binding of S aureus to the skin of patients with AD. (J Allergy Clin Immunol 2001;108:269-74.)