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

Author

Listed:
  • 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
    Heidelberg University Hospital)

  • Friedrich Götz

    (University of Tübingen)

  • Bernhard Krismer

    (University of Tübingen
    Partner Site Tübingen)

  • Andreas Peschel

    (University of Tübingen
    Partner Site Tübingen)

  • Birgit Schittek

    (University of Tübingen)

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.

Suggested Citation

  • Katharina Bitschar & Birgit Sauer & Jule Focken & Hanna Dehmer & Sonja Moos & Martin Konnerth & Nadine A. Schilling & Stephanie Grond & Hubert Kalbacher & Florian C. Kurschus & Friedrich Götz & Bernha, 2019. "Lugdunin amplifies innate immune responses in the skin in synergy with host- and microbiota-derived factors," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10646-7
    DOI: 10.1038/s41467-019-10646-7
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    Cited by:

    1. Dominik Ruppelt & Marius F. W. Trollmann & Taulant Dema & Sebastian N. Wirtz & Hendrik Flegel & Sophia Mönnikes & Stephanie Grond & Rainer A. Böckmann & Claudia Steinem, 2024. "The antimicrobial fibupeptide lugdunin forms water-filled channel structures in lipid membranes," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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