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

Abstract

<i>Staphylococcus aureus</i> colonizes the skin of the majority of patients with atopic dermatitis (AD), and its presence increases disease severity. Adhesion of <i>S. aureus</i> to 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 that <i>S. aureus</i> interacts 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). An <i>S. aureus</i> mutant 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. The <i>S. aureus</i> binding 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 individual <i>S. aureus</i> cells to corneocytes. Finally, we found that <i>S. aureus</i> mutants 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, allowing <i>S. aureus</i> to take advantage of the aberrant display of corneodesmosin that accompanies low NMF in AD. This interaction facilitates the characteristic strong binding of <i>S. aureus</i> to AD corneocytes.