Bacterial MazF/MazE toxin-antitoxin suppresses lytic propagation of arbitrium-containing phages

Temperate phages dynamically switch between lysis and lysogeny in their full life cycle. Some Bacillus-infecting phages utilize a quorum-sensing-like intercellular communication system, the “arbitrium,” to mediate lysis-lysogeny decisions. However, whether additional factors participate in the arbitrium signaling pathway remains largely elusive. Here, we find that the arbitrium signal induces the expression of a functionally conserved operon downstream of the arbitrium module in SPbeta-like phages. SPbeta yopM and yopR (as well as phi3T phi3T_93 and phi3T_97) in the operon play roles in suppressing phage lytic propagation and promoting lysogeny, respectively. We further focus on phi3T_93 and demonstrate that it directly binds antitoxin MazE in the host MazF/MazE toxin-antitoxin (TA) module and facilitates the activation of MazF’s toxicity, which is required for phage suppression. These findings show events regulated by the arbitrium system and shed light on how the interplay between phages and the host TA module affects phage-host co-survival. [Display omitted] •Phage arbitrium system induces the expression of a downstream operon•Two genes in this operon influence phage lytic/lysogenic infection•Phage YopM (phi3T_93) binds the host MazF/MazE module and activates MazF toxin•MazF/MazE module suppresses phage lytic propagation via abortive infection Some temperate phages utilize a quorum-sensing-like intercellular communication system, the “arbitrium,” to mediate lysis-lysogeny decisions, but downstream events in the arbitrium signaling pathway remain largely elusive. Cui et al. show that for SPbeta-like phages, an arbitrium-regulated phage protein and a host toxin-antitoxin module together control phage lytic propagation.