Lugdunin amplifies innate immune responses in the skin in synergy with host- and microbiota-derived factors

Recently our groups discovered lugdunin, a new cyclic peptide antibiotic that inhibits S taphylococcus aureus epithelial colonization in humans and rodents. In this work, we analyzed its immuno-modulatory and antimicrobial potential as a single agent or in combination with other microbiota- or host-...

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Veröffentlicht in:Nature communications 2019-06, Vol.10 (1), p.2730-14, Article 2730
Hauptverfasser: Bitschar, Katharina, Sauer, Birgit, Focken, Jule, Dehmer, Hanna, Moos, Sonja, Konnerth, Martin, Schilling, Nadine A., Grond, Stephanie, Kalbacher, Hubert, Kurschus, Florian C., Götz, Friedrich, Krismer, Bernhard, Peschel, Andreas, Schittek, Birgit
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Sprache:eng
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Zusammenfassung:Recently our groups discovered lugdunin, a new cyclic peptide antibiotic that inhibits S taphylococcus aureus epithelial colonization in humans and rodents. In this work, we analyzed its immuno-modulatory and antimicrobial potential as a single agent or in combination with other microbiota- or host-derived factors. We show that pretreatment of primary human keratinocytes or mouse skin with lugdunin in combination with microbiota-derived factors results in a significant reduction of S. aureus colonization. Moreover, lugdunin increases expression and release of LL-37 and CXCL8/MIP-2 in human keratinocytes and mouse skin, and results in the recruitment of monocytes and neutrophils in vivo, both by a TLR/MyD88-dependent mechanism. Interestingly, S. aureus elimination by lugdunin is additionally achieved by synergistic antimicrobial activity with LL-37 and dermcidin-derived peptides. In summary, our results indicate that lugdunin provides multi-level protection against S. aureus and may thus become a promising treatment option for S. aureus skin infections in the future. Lugdunin is a peptide antibiotic produced by the skin commensal Staphylococcus lugdunensis . Here, the authors show that lugdunin reduces Staphylococcus aureus colonization in human keratinocytes and mouse skin by inducing the expression of human LL-37 and recruitment of monocytes and neutrophils.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-019-10646-7