Temperate phage evolve to integrate host stress and quorum signals in lysis–lysogeny decisions

Temperate phage can transmit both horizontally (lytic cycle) and vertically (lysogenic cycle). Many temperate phage have the ability to modify their lysis/lysogeny decisions based on various environmental cues. For instance, many prophage are known to reactivate when SOS stress responses of their host are triggered. Temperate phage infecting Bacilli can also use peptide signals ("arbitrium") to control their lysis/lysogeny decisions. However, information from the arbitrium and SOS systems can be potentially conflicting, and it is unclear how phage integrate information carried by these two different signals when making lysis-lysogeny decisions. Here, we use evolutionary epidemiology theory to explore how phage could evolve to use both systems to modulate lysis/lysogeny decisions in a fluctuating environment. Our model predicts that it can be adaptive for phage to respond to both host SOS systems and arbitrium signaling, as they provide complementary information on the quality of the infected host and the availability of alternative hosts. Using the phage phi3T and its host Bacillus subtilis, we show that during lytic infection and as prophage, lysis-lysogeny decisions rely on the integration of information on host condition and arbitrium signal concentrations. For example, free-phage are more likely to lysogenise a stressed host, and prophage are less likely to abandon a stressed host, when high arbitrium concentrations suggest susceptible hosts are unavailable. These experimental results are consistent with our theoretical predictions and demonstrate that phage can evolve plastic life-history strategies to adjust their infection dynamics to account for both the within-host environment (host quality) and the external environment that exists outside of their host (availability of susceptible hosts in the population). More generally, our work yields a new theoretical framework to study the evolution of viral plasticity under the influence of multiple environmental cues.