2. Academic Validation
  3. Commensal production of a broad-spectrum and short-lived antimicrobial peptide polyene eliminates nasal Staphylococcus aureus

Commensal production of a broad-spectrum and short-lived antimicrobial peptide polyene eliminates nasal Staphylococcus aureus

  • Nat Microbiol. 2024 Jan;9(1):200-213. doi: 10.1038/s41564-023-01544-2.
Benjamin O Torres Salazar # 1 2 3,  Taulant Dema # 4,  Nadine A Schilling 2 4,  Daniela Janek 1 2 3,  Jan Bornikoel 5,  Anne Berscheid 3 5,  Ahmed M A Elsherbini 1 2 3,  Sophia Krauss 1 2 3,  Simon J Jaag 6,  Michael Lämmerhofer 6,  Min Li 7,  Norah Alqahtani 8,  Malcolm J Horsburgh 8,  Tilmann Weber 9,  José Manuel Beltrán-Beleña 2 4,  Heike Brötz-Oesterhelt 3 5,  Stephanie Grond 10 11,  Bernhard Krismer 12 13 14,  Andreas Peschel 1 2 3
Affiliations

Affiliations

  • 1 Department of Infection Biology, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
  • 2 Cluster of Excellence EXC 2124 Controlling Microbes to Fight Infections, Tübingen, Germany.
  • 3 German Center for Infection Research (DZIF), partner site Tübingen, Tübingen, Germany.
  • 4 Institute of Organic Chemistry, University of Tübingen, Tübingen, Germany.
  • 5 Department of Microbial Bioactive Compounds, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
  • 6 Institute of Pharmaceutical Sciences, University of Tübingen, Tübingen, Germany.
  • 7 Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
  • 8 Department of Infection Biology and Microbiomes, University of Liverpool, Liverpool, UK.
  • 9 The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kongens Lyngby, Denmark.
  • 10 Cluster of Excellence EXC 2124 Controlling Microbes to Fight Infections, Tübingen, Germany. stephanie.grond@uni-tuebingen.de.
  • 11 Institute of Organic Chemistry, University of Tübingen, Tübingen, Germany. stephanie.grond@uni-tuebingen.de.
  • 12 Department of Infection Biology, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany. b.krismer@uni-tuebingen.de.
  • 13 Cluster of Excellence EXC 2124 Controlling Microbes to Fight Infections, Tübingen, Germany. b.krismer@uni-tuebingen.de.
  • 14 German Center for Infection Research (DZIF), partner site Tübingen, Tübingen, Germany. b.krismer@uni-tuebingen.de.
  • # Contributed equally.
PMID: 38110697 DOI: 10.1038/s41564-023-01544-2
Abstract

Antagonistic Bacterial interactions often rely on antimicrobial bacteriocins, which attack only a narrow range of target bacteria. However, antimicrobials with broader activity may be advantageous. Here we identify an antimicrobial called epifadin, which is produced by nasal Staphylococcus epidermidis IVK83. It has an unprecedented architecture consisting of a non-ribosomally synthesized peptide, a polyketide component and a terminal modified amino acid moiety. Epifadin combines a wide antimicrobial target spectrum with a short life span of only a few hours. It is highly unstable under in vivo-like conditions, potentially as a means to limit collateral damage of Bacterial mutualists. However, Staphylococcus aureus is eliminated by epifadin-producing S. epidermidis during co-cultivation in vitro and in vivo, indicating that epifadin-producing commensals could help prevent nasal S. aureus carriage. These insights into a microbiome-derived, previously unknown antimicrobial compound class suggest that limiting the half-life of an antimicrobial may help to balance its beneficial and detrimental activities.

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