What makes a temperate phage an effective bacterial weapon?

Abstract Temperate bacteriophages (phages) are common features of bacterial genomes and can act as self-amplifying biological weapons, killing susceptible competitors and thus increasing the fitness of their bacterial hosts (lysogens). Despite their prevalence, however, the key characteristics of an effective temperate phage weapon remain unclear. Here we use systematic mathematical analyses coupled with experimental tests to understand what makes an effective temperate phage weapon. We find that effectiveness is controlled by phage life history traits – in particular, the probability of lysis, and induction rate – but that the optimal combination of traits varies with the initial frequency of a lysogen within a population. As a consequence, certain phage weapons can be detrimental when their hosts are rare, yet beneficial when their hosts are common, while subtle changes in individual life history traits can completely reverse the impact of an individual phage weapon on lysogen fitness. We confirm key predictions of our model experimentally, using temperate phages isolated from the clinically relevant Liverpool Epidemic Strain of Pseudomonas aeruginosa . Through these experiments, we further demonstrate that nutrient availability can also play a critical role in driving frequency-dependent patterns in phage-mediated competition. Together, these findings highlight the complex and context-dependent nature of temperate phage weapons, and highlight the importance of both ecological and evolutionary processes in shaping microbial community dynamics more broadly. Importance Temperate bacteriophage – viruses that integrate within bacterial DNA – are incredibly common within bacterial genomes. These phages are thought to act as powerful self-amplifying weapons, allowing their bacterial hosts to kill nearby competitors and thus gain a fitness advantage within a given niche. But what makes an effective phage weapon? Here we first use a simple mathematical model to explore the factors determining phage weapon utility. Our models suggest that phage weapons are nuanced and context-dependent: an individual phage may be beneficial or costly depending upon tiny changes to how it behaves, or to the bacterial community in which it resides. We then confirm these mathematical predictions experimentally, using phage isolated from Cystic Fibrosis patients. But, in doing so, we also find that another factor – nutrient availability – plays a key role in shaping phage-mediated competition. Together our results provide new insights into how temperate phage modulate bacterial communities.