Zamora-Caballero, S., Chmielowska, C., Quiles-Puchalt, N., Brady, A., del Sol, F. G., Mancheño-Bonillo, J., Felipe-Ruíz, A., Meijer, W. J. J., Penadés, J. R. and Marina, A. (2024) Antagonistic interactions between phage and host factors control arbitrium lysis–lysogeny decision. Nature Microbiology, 9, pp. 161-172. (doi: 10.1038/s41564-023-01550-4) (PMID:38177302) (PMCID:PMC10769878)
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Abstract
Phages can use a small-molecule communication arbitrium system to coordinate lysis–lysogeny decisions, but the underlying mechanism remains unknown. Here we determined that the arbitrium system in Bacillus subtilis phage phi3T modulates the bacterial toxin–antitoxin system MazE–MazF to regulate the phage life cycle. We show that phi3T expresses AimX and YosL, which bind to and inactivate MazF. AimX also inhibits the function of phi3T_93, a protein that promotes lysogeny by binding to MazE and releasing MazF. Overall, these mutually exclusive interactions promote the lytic cycle of the phage. After several rounds of infection, the phage-encoded AimP peptide accumulates intracellularly and inactivates the phage antiterminator AimR, a process that eliminates aimX expression from the aimP promoter. Therefore, when AimP increases, MazF activity promotes reversion back to lysogeny, since AimX is absent. Altogether, our study reveals the evolutionary strategy used by arbitrium to control lysis–lysogeny by domesticating and fine-tuning a phage-defence mechanism.
| Item Type: | Articles |
|---|---|
| Additional Information: | This work was supported by grants PID2019-108541GB-I00 and PID2022-137201NB-I00 from the Spanish Government (Ministerio de Ciencia e Innovación), PROMETEO/2020/012 by the Valencian Government and the European Commission NextGenerationEU fund (EU 2020/2094), through CSIC’s Global Health Platform (PTI Salud Global) to A.M., and grants MR/M003876/1, MR/V000772/1 and MR/ S00940X/1 from the Medical Research Council (UK), BB/N002873/1, BB/V002376/1 and BB/S003835/1 from the Biotechnology and Biological Sciences Research Council (BBSRC, UK), ERC-ADG-2014 Proposal no. 670932 Dut-signal (from EU), and Wellcome Trust 201531/Z/16/Z to J.R.P. A.F.-R. received an FPU predoctoral fellowship from the Spanish Ministry of Universities, reference FPU19/00433. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Brady, Miss Aisling |
| Authors: | Zamora-Caballero, S., Chmielowska, C., Quiles-Puchalt, N., Brady, A., del Sol, F. G., Mancheño-Bonillo, J., Felipe-Ruíz, A., Meijer, W. J. J., Penadés, J. R., and Marina, A. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Nature Microbiology |
| Publisher: | Nature Research |
| ISSN: | 2058-5276 |
| ISSN (Online): | 2058-5276 |
| Published Online: | 04 January 2024 |
| Copyright Holders: | Copyright © The Authors 2024 |
| First Published: | First published in Nature Microbiology 9:161–172 |
| Publisher Policy: | Reproduced under a Creative Commons licence |
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