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

Abstract

Colonization of the skin by <i>Staphylococcus aureus</i> 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 <i>S. aureus</i> 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 <i>S. aureus agr</i> system, in turn decreasing PSMα expression. These autoinducing peptides from skin microbiome CoNS species potently suppressed PSMα expression in <i>S. aureus</i> isolates from subjects with AD without inhibiting <i>S. aureus</i> growth. Metagenomic analysis of the AD skin microbiome revealed that the increase in the relative abundance of <i>S. aureus</i> in patients with active AD correlated with a lower CoNS autoinducing peptides to <i>S. aureus</i> ratio, thus overcoming the peptides' capacity to inhibit the <i>S. aureus agr</i> system. Characterization of a <i>S. hominis</i> clinical isolate identified an autoinducing peptide (SYNVCGGYF) as a highly potent inhibitor of <i>S. aureus agr</i> activity, capable of preventing <i>S. aureus</i>-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 <i>S. aureus</i> toxin production.