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

Katharina Bitschar, Birgit Sauer, Jule Focken, Hanna Dehmer, Sonja Moos, Martin Konnerth, Nadine A. Schilling, Stephanie Grond, Hubert Kalbacher, Florian C. Kurschus, Friedrich Götz, Bernhard Krismer, Andreas Peschel and Birgit Schittek ()
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Katharina Bitschar: University of Tübingen
Birgit Sauer: University of Tübingen
Jule Focken: University of Tübingen
Hanna Dehmer: University of Tübingen
Sonja Moos: University Medical Center of the Johannes Gutenberg-University Mainz
Martin Konnerth: University of Tübingen
Nadine A. Schilling: University of Tübingen
Stephanie Grond: University of Tübingen
Hubert Kalbacher: University of Tübingen
Florian C. Kurschus: University Medical Center of the Johannes Gutenberg-University Mainz
Friedrich Götz: University of Tübingen
Bernhard Krismer: University of Tübingen
Andreas Peschel: University of Tübingen
Birgit Schittek: University of Tübingen

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-10646-7

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