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

Abstract

Staphylococcus aureuscolonizes the skin of the majority of patients with atopic dermatitis (AD), and its presence increases disease severity. Adhesion ofS. aureusto corneocytes in the stratum corneum is a key initial event in colonization, but the bacterial and host factors contributing to this process have not been defined. Here, we show thatS. aureusinteracts with the host protein corneodesmosin. Corneodesmosin is aberrantly displayed on the tips of villus-like projections that occur on the surface of AD corneocytes as a result of low levels of skin humectants known as natural moisturizing factor (NMF). AnS. aureusmutant deficient in fibronectin binding protein B (FnBPB) and clumping factor B (ClfB) did not bind to corneodesmosin in vitro. Using surface plasmon resonance, we found that FnBPB and ClfB proteins bound with similar affinities. TheS. aureusbinding site was localized to the N-terminal glycine–serine-rich region of corneodesmosin. Atomic force microscopy showed that the N-terminal region was present on corneocytes containing low levels of NMF and that blocking it with an antibody inhibited binding of individualS. aureuscells to corneocytes. Finally, we found thatS. aureusmutants deficient in FnBPB or ClfB have a reduced ability to adhere to low-NMF corneocytes from patients. In summary, we show that FnBPB and ClfB interact with the accessible N-terminal region of corneodesmosin on AD corneocytes, allowingS. aureusto take advantage of the aberrant display of corneodesmosin that accompanies low NMF in AD. This interaction facilitates the characteristic strong binding ofS. aureusto AD corneocytes.