A DNA recognition-mimicry switch governs induction in arbitrium phages
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.
Authors
- Avigdor Eldar (ORCID: https://orcid.org/0000-0001-8485-9370)
- Cora Chmielowska (ORCID: https://orcid.org/0000-0001-7051-3432)
- Tom Borenstein (ORCID: https://orcid.org/0009-0005-9352-3138)
- Daniel Sin (ORCID: https://orcid.org/0000-0002-5491-0451)
- Javier Mancheño-Bonillo
- José R. Penadés
- Alberto Marina
- Shira Omer Bendori
- Yuyi Li
- Sara Zamora-Caballero
Institutions
- Tel Aviv University (IL)
- NIHR Imperial Biomedical Research Centre (GB)
- Instituto de Biomedicina de Valencia (ES)
- Imperial College London (GB)
Publication Details
- Journal
- Cell Host & Microbe
- Published
- 2026-01-30
- DOI
- https://doi.org/10.1016/j.chom.2026.01.012
- Citations
- 1
- Primary Topic
- Bacteriophages and microbial interactions
- Type
- article
- Field-Weighted Citation Impact
- 31.91
Funders
- European Commission
- Directorate for Biological Sciences
- Medical Research Council
- Engineering and Physical Sciences Research Council
- Biotechnology and Biological Sciences Research Council