Shmunis School of Biomedicine and Cancer Research, Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel.
Department of Biochemistry and Molecular Biology, Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel.
Nat Microbiol. 2024 Jan;9(1):150-160. doi: 10.1038/s41564-023-01551-3. Epub 2024 Jan 4.
Temperate Bacillus phages often utilize arbitrium communication to control lysis/lysogeny decisions, but the mechanisms by which this control is exerted remains largely unknown. Here we find that the arbitrium system of Bacillus subtilis phage ϕ3T modulates the host-encoded MazEF toxin-antitoxin system to this aim. Upon infection, the MazF ribonuclease is activated by three phage genes. At low arbitrium signal concentrations, MazF is inactivated by two phage-encoded MazE homologues: the arbitrium-controlled AimX and the later-expressed YosL proteins. At high signal, MazF remains active, promoting lysogeny without harming the bacterial host. MazF cleavage sites are enriched on transcripts of phage lytic genes but absent from the phage repressor in ϕ3T and other Spβ-like phages. Combined with low activation levels of MazF during infections, this pattern explains the phage-specific effect. Our results show how a bacterial toxin-antitoxin system has been co-opted by a phage to control lysis/lysogeny decisions without compromising host viability.
温带芽孢杆菌噬菌体通常利用仲裁通讯来控制裂解/溶原决策,但这种控制的机制在很大程度上仍不清楚。在这里,我们发现枯草芽孢杆菌噬菌体 ϕ3T 的仲裁系统调节了宿主编码的 MazEF 毒素-抗毒素系统以达到这一目的。感染后,MazF 核糖核酸酶被三个噬菌体基因激活。在低仲裁信号浓度下,MazF 被两个噬菌体编码的 MazE 同源物失活:仲裁控制的 AimX 和稍后表达的 YosL 蛋白。在高信号下,MazF 仍然保持活性,促进溶原而不伤害细菌宿主。MazF 切割位点在噬菌体裂解基因的转录本中富集,但在 ϕ3T 和其他 Spβ 样噬菌体中的噬菌体阻遏物中不存在。结合感染过程中 MazF 的低激活水平,这种模式解释了噬菌体的特异性效应。我们的研究结果表明,细菌毒素-抗毒素系统如何被噬菌体劫持来控制裂解/溶原决策,而不会危及宿主的生存能力。