What makes a temperate phage an effective bacterial weapon?

Abstract

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 the importance of both ecological and evolutionary processes in shaping microbial community dynamics more broadly.IMPORTANCETemperate bacteriophages—viruses that integrate within bacterial DNA—are incredibly common within bacterial genomes and can act as powerful self-amplifying weapons. Bacterial hosts that carry temperate bacteriophages can thus gain a fitness advantage within a given niche by killing competitors. But what makes an effective phage weapon? Here, we first use a simple mathematical model to explore the factors determining bacteriophage weapon utility. Our models suggest that bacteriophage weapons are nuanced and context-dependent; an individual bacteriophage may be beneficial or costly depending upon tiny changes to how it behaves or the bacterial community it inhabits. We then confirm these mathematical predictions experimentally, using phages isolated from cystic fibrosis patients. But, in doing so, we also find that another factor—nutrient availability—plays a key role in shaping bacteriophage-mediated competition. Together, our results provide new insights into how temperate bacteriophages modulate bacterial communities.

Keywords

• bacteriophages
• microbial ecology
• mathematical modeling
• temperate phage
• bacterial weapons
• microbial evolution