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

Williams, Michael R.; Costa, Stephen K.; Zaramela, Livia S.; Khalil, Shadi; Todd, Daniel A.; Winter, Heather L.; Sanford, James A.; O'Neill, Alan M.; Liggins, Marc C.; Nakatsuji, Teruaki; Cech, Nadja B.; Cheung, Ambrose L.; Zengler, Karsten; Horswill, Alexander R.; Gallo, Richard L.

Quorum sensing peptides produced by commensal skin staphylococci protect against skin injury and inflammation induced by Staphylococcus aureus toxins. Skin-soothing bacteria: Staphylococcus aureus is both a normal skin-resident species and a common bad actor in inflammatory skin conditions. Williams et al. showed that S. aureus relies on quorum sensing to secrete certain toxins and proteases that can cause epithelial barrier damage. Coagulase-negative staphylococci (CoNS) normally present on human skin, however, secreted autoinducing peptides that inhibited quorum sensing in S. aureus and hence secretion of these virulence factors. A CoNS autoinducing peptide also reduced S. aureus–induced skin inflammation in mice. Analysis of the skin microbiome of patients with atopic dermatitis suggested that the ratio of protective CoNS to S. aureus may be a factor in the pathogenesis of this condition. Colonization of the skin by Staphylococcus aureus 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 S. aureus 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 S. aureus agr system, in turn decreasing PSMα expression. These autoinducing peptides from skin microbiome CoNS species potently suppressed PSMα expression in S. aureus isolates from subjects with AD without inhibiting S. aureus growth. Metagenomic analysis of the AD skin microbiome revealed that the increase in the relative abundance of S. aureus in patients with active AD correlated with a lower CoNS autoinducing peptides to S. aureus ratio, thus overcoming the peptides' capacity to inhibit the S. aureus agr system. Characterization of a S. hominis clinical isolate identified an autoinducing peptide (SYNVCGGYF) as a highly potent inhibitor of S. aureus agr activity, capable of preventing S. aureus–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 S. aureus toxin production.

QUORUM sensing; ATOPIC dermatitis; EPIDERMAL diseases; PEPTIDES; STAPHYLOCOCCUS aureus; PROTEOLYSIS

Science Translational Medicine, 2019, Vol 11, Issue 490, pN.PAG

1946-6234

Academic Journal

10.1126/scitranslmed.aat8329