Glycan-Dependent Corneocyte Adherence of Staphylococcus epidermidis Mediated by the Lectin Subdomain of Aap

Staphylococcus epidermidis and other coagulase-negative staphylococci (CoNS) that colonize skin are known to promote skin immunity and inhibit colonization of pathogens that cause skin and soft tissue infections, including Staphylococcus aureus. However, S. epidermidis adherence to corneocytes, the cells that constitute the uppermost layer of the skin epidermis, remains poorly understood. Our study documents that S. epidermidis corneocyte adherence is dependent upon the accumulation-associated protein (Aap). Aap is composed of two distinct A and B domains. The A domain is comprised of a repeat region and a conserved L-type lectin domain, whereas the fibrillar B domain, which is comprised of G5 and E repeats, is linked to the cell wall in a sortase-dependent manner. Our studies revealed that adherence to corneocytes is dependent upon the lectin subdomain within the A domain. However, significant adherence was only observed when the lectin domain was expressed with both the A repeat and the B domain, suggesting further interactions between these three domains. Our data also suggest that the A repeat domain is important for stability or expression of Aap. Deglycosylation treatment suggested that glycans expressed in the host stratum corneum serve as potential binding partners for Aap-mediated corneocyte adherence. Last, bioinformatic analyses of the predominant commensal species of CoNS identified open reading frames (ORFs) homologous to aap, thus suggesting that Aap orthologues containing lectin-like domains may provide the basis for staphylococcal colonization of skin. Corroborating these observations, adherence to corneocytes in an S. aureus mgrA mutant was dependent upon SasG, the Aap orthologue in S. aureus.