Quorum sensing between bacterial species on the skin protects against epidermal injury in atopic dermatitis.

Colonization of the skin by is associated with exacerbation of atopic dermatitis (AD), but any direct mechanism through which dysbiosis of the skin microbiome may influence the development of AD is unknown. Here, we show that proteases and phenol-soluble modulin α (PSMα) secreted by lead to endogenous epidermal proteolysis and skin barrier damage that promoted inflammation in mice. We further show that clinical isolates of different coagulase-negative staphylococci (CoNS) species residing on normal skin produced autoinducing peptides that inhibited the system, in turn decreasing PSMα expression. These autoinducing peptides from skin microbiome CoNS species potently suppressed PSMα expression in isolates from subjects with AD without inhibiting growth. Metagenomic analysis of the AD skin microbiome revealed that the increase in the relative abundance of in patients with active AD correlated with a lower CoNS autoinducing peptides to ratio, thus overcoming the peptides' capacity to inhibit the system. Characterization of a clinical isolate identified an autoinducing peptide (SYNVCGGYF) as a highly potent inhibitor of activity, capable of preventing -mediated epithelial damage and inflammation on murine skin. Together, these findings show how members of the normal human skin microbiome can contribute to epithelial barrier homeostasis by using quorum sensing to inhibit toxin production.