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 |
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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. |
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ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/s41467-019-10646-7 |