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Nat Commun. 2019 Jun 21;10(1):2730. doi: 10.1038/s41467-019-10646-7.

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

Author information

1
Department of Dermatology, University of Tübingen, Liebermeisterstraße 25, 72076, Tübingen, Germany.
2
Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131, Mainz, Germany.
3
Institute of Organic Chemistry, University of Tübingen, Auf der Morgenstelle 18, 72076, Tübingen, Germany.
4
Interfaculty Institute of Biochemistry, University of Tübingen, Ob dem Himmelreich 7, 72074, Tübingen, Germany.
5
Department of Dermatology, Heidelberg University Hospital, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany.
6
Interfaculty Institute of Microbiology and Infection Medicine, Microbial Genetics, University of Tübingen, Auf der Morgenstelle 28, 72076, Tübingen, Germany.
7
Interfaculty Institute of Microbiology and Infection Medicine, Infection Biology, University of Tübingen, Auf der Morgenstelle 28, 72076, Tübingen, Germany.
8
German Centre for Infection Research (DZIF), Partner Site Tübingen, Auf der Morgenstelle 28, 72076, Tübingen, Germany.
9
Department of Dermatology, University of Tübingen, Liebermeisterstraße 25, 72076, Tübingen, Germany. Birgit.schittek@med.uni-tuebingen.de.

Abstract

Recently our groups discovered lugdunin, a new cyclic peptide antibiotic that inhibits Staphylococcus 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.

PMID:
31227691
PMCID:
PMC6588697
DOI:
10.1038/s41467-019-10646-7
[Indexed for MEDLINE]
Free PMC Article

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