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

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Nadja B. Cech, Patricia A. Sullivan Distinguished Professor of Chemistry (Creator)
Daniel A. Todd (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/

Abstract: 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 a (PSMa) 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 PSMa expression. These autoinducing peptides from skin microbiome CoNS species potently suppressed PSMa 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.

Additional Information

Science Translational Medicine 11(490), eaat8329
Language: English
Date: 2019
atopic dermatitis, skin microbiome, Staphylococcus aureus, coagulase-negative staphylococci (CoNS)

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