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A DNA recognition-mimicry switch governs induction in arbitrium phages

  • Cora Chmielowska
  • , Sara Zamora-Caballero
  • , Javier Mancheño-Bonillo
  • , Yuyi Li
  • , Daniel Sin
  • , Tom Borenstein
  • , Shira Omer Bendori
  • , Avigdor Eldar
  • , Alberto Marina*
  • , José R. Penadés*
  • *Corresponding author for this work
  • Department of Infectious Diseases
  • Imperial College London
  • Centre for Bacterial Resistance Biology
  • Centro de Investigación Biomédica en Red
  • Veterinary School
  • CEU Universities

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Temperate phages integrate multiple information sources to regulate lysis-lysogeny transitions. SPbeta-like phages use arbitrium signaling and DNA damage to control repressor activity during lytic induction, but how the repressor functions and is inactivated by the SOS response remains unclear. Here, we show that SroF, the SPbeta-like phage repressor, binds DNA via a mechanism involving its integrase-like fold, enabling stable prophage repression. Upon DNA damage, the host SOS response triggers derepression of an antirepressor, Sar. Sar binds SroF by mimicking the DNA structure recognized by the repressor, thereby inactivating its function and inducing phage. This mechanism is conserved across SPbeta-like phages, which encode multiple, specific SroF-Sar pairs. Surprisingly, repressor inactivation alone is insufficient for efficient induction when arbitrium levels are high. Our results uncover the mechanism underlying a double layer of control that ensures phage induction occurs only under SOS conditions and in the absence of neighboring prophages.

Original languageEnglish
Pages (from-to)291-303.e10
JournalCell Host and Microbe
Volume34
Issue number2
DOIs
StatePublished - 11 Feb 2026

Funding

FundersFunder number
Scientific Network Conexión Resistencia Antimicrobianos
Valencian Government
Engineering and Physical Sciences Research Council
European CommissionMR/M003876/1, MR/V000772/1, MR/X020223/1, MR/S00940X/1, EU 2020/2094
Biotechnology and Biological Sciences Research CouncilEP/X026671/1
European Research Council101118890
Medical Research CouncilBB/V002376/1, BB/V009583/1
Ministerio de Ciencia e InnovaciónCIPROM/2023/30
Consejo Superior de Investigaciones CientíficasPID2022-137201NB-I00

    Keywords

    • DNA damage
    • SOS response
    • activator
    • lysis-lysogeny decision
    • quorum sensing
    • repressor
    • temperate phages

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