Bacterial peptide deformylase inhibitors induce prophages in competitors.

bioRxiv : the preprint server for biology
Authors
Abstract

While antibiotics mediate chemical warfare among microbes, their roles in the wild extend beyond direct growth inhibition(1). Some antibiotics have the potential to mediate interference competition by triggering a bacterial stress response that subsequently activates endogenous viruses integrated in bacterial genomes (prophages). Canonically, this activation is regulated by the SOS response upon DNA damage. Here we show that a metabolite produced by natural isolates of circumvents the SOS response by directly triggering prophage induction in other species, co-occurring in the same environment. While the metabolite was previously classified as a broad-spectrum antibiotic, we observe how it acts as a peptide deformylase inhibitor that specifically induces certain prophages, even when target bacterial cells carry multiple other prophages. Its biosynthetic gene cluster, or cluster, also encodes its own peptide deformylase (OrdE) which provides self-immunity to producer strains. Likewise, among natural isolates that carry similar prophages, resistance against the metabolite was found in those that had acquired a divergent second peptide deformylase. Finally, we show that prophage induction by the cluster prevents slower-growing producer strains from being outcompeted by their otherwise fast-growing competitors if they carry an inducible prophage. Thus, we demonstrate how natural products play additional impactful roles in communities beyond antibiotic activity and that prophage induction serves as an interference competition strategy, sustaining community diversity.

Year of Publication
2025
Journal
bioRxiv : the preprint server for biology
Date Published
06/2025
ISSN
2692-8205
DOI
10.1101/2025.06.06.656871
PubMed ID
40501655
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