Arbitrium communication controls phage life-cycle through modulation of a bacterial anti-phage defense system

Abstract Bacterial temperate viruses (phages) have to decide between a quiescent (lysogenic) and virulent (lytic) lifestyle in the face of a variety of phage defense systems. Multiple Bacilli phage families have been shown to use the arbitrium communication system, but the mechanism by which the arbitrium system exerts its function remains largely unknown. Here we study phage ?3T, in which arbitrium was originally identified, and find that arbitrium communication controls the phage life-cycle through interactions with a host-encoded defense system. Under lytic conditions, the arbitrium system expresses an anti-toxin, AimX, which blocks the RNA ribonuclease activity of MazF, part of the MazEF toxin-antitoxin system. When arbitrium signal concentration is high, AimX is not expressed and MazF remains active. We find that this activity is necessary for lysogenization. Finally, we show that MazEF acts as a defense system, and protects bacteria against a lytic ?3T mutant which lacks AimX and an additional later-expressed MazE-like antitoxin, YosL. Altogether, our results show how a bacterial defense system has been co-opted by phages to control their lysis/lysogeny decision-making.