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

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

  • Nat Commun. 2019 Jun 21;10(1):2730. doi: 10.1038/s41467-019-10646-7.
Katharina Bitschar 1,  Birgit Sauer 1,  Jule Focken 1,  Hanna Dehmer 1,  Sonja Moos 2,  Martin Konnerth 3,  Nadine A Schilling 3,  Stephanie Grond 3,  Hubert Kalbacher 4,  Florian C Kurschus 2 5,  Friedrich Götz 6,  Bernhard Krismer 7 8,  Andreas Peschel 7 8,  Birgit Schittek 9
Affiliations

Affiliations

  • 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. [email protected].
PMID: 31227691 DOI: 10.1038/s41467-019-10646-7
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.

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