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

Benjamin O. Torres Salazar, Taulant Dema, Nadine A. Schilling, Daniela Janek, Jan Bornikoel, Anne Berscheid, Ahmed M.A. Elsherbini, Sophia Krauss, Simon J. Jaag, Michael Lämmerhofer, Min Li, Norah Alqahtani, Malcolm J. Horsburgh, Tilmann Weber, José Manuel Beltrán-Beleña, Heike Brötz-Oesterhelt, Stephanie Grond*, Bernhard Krismer*, Andreas Peschel

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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.

Original languageEnglish
JournalNature Microbiology
Volume9
Issue number1
Pages (from-to)200-213
Number of pages14
ISSN2058-5276
DOIs
Publication statusPublished - 2024

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