Aaron Smith, Michael Hunter, Somenath Bakshi, Diana Fusco
Bacteriophages (phages) play a critical role in controlling bacterial populations, both in nature and as potential therapeutic agents. Their ability to replicate, compete against each other, and eradicate target cell populations is usually understood through a number of 'life history parameters', traditionally measured by population-level assays, which implicitly average the parameter's value across a large number of infection events. Recent experiments suggest that bacteriophage life history parameters are subject to considerable stochasticity, raising the question of whether experimental and modelling efforts that do not account for this variability may overlook important factors in phage's behaviour, competitive fitness or therapeutic viability. Here, using agent-based simulations, we investigate the importance of stochasticity in lysis time and burst size of lytic bacteriophages in two common laboratory competition experiments: serial passage of well-mixed populations and plaque expansion across a bacterial lawn. We find that a phage's analytic growth rate in isolation can be a poor predictor of its fitness advantage in simulated competition experiments. Specifically, when lysis times are tightly distributed, we identify a novel effect we name "population resonance", through which a bacteriophage can display a significant fitness advantage over a competitor with a much greater growth rate in isolation. Our simulations also show that both serial passage and plaque expansion reward variability in lysis time more than expected, by increasing the phage resilience when resources are scarce.