Host Physiology–Dependent Lysis Timing Shapes Bacteriophage Competition Under Nutrient Fluctuations

When bacteriophages infect starved host bacteria, the restrictive host physiology may lead to prolonged latent periods and/or reduced burst sizes, compared to infection of a fast-growing bacterium. Using a mathematical model, we explore a system of two types of virulent phages that have distinct host physiology dependencies and are infecting a shared bacterial host population. We consider different environmental regimes to test whether they can compete and coexist under fluctuating conditions, putting emphasis on phases with limited resources for bacterial growth. We find that phages capable of delaying lysis in response to nutrient limitations can outcompete fast-replicating phages in feast-famine environments. This advantage mainly stems from increased mortality of free phages due to abortive adsorption to already infected hosts during starvation phases. We identify specific system dynamics that either support or suppress the propagation of the delayed lysis phage. This theoretical analysis highlights the competitive benefits and the limitations of delayed lysis as a phage propagation strategy. Our results underscore importance of considering the bacterial physiology dependence of bacteriophage replication in order to correctly predict phage fitness and population dynamics in complex environments.