Counting to two: how phages decide between lysis and lysogeny

Abstract

Upon infecting a bacterium, temperate phages must decide between killing the cell to reproduce (lysis) and entering a symbiotic lifestyle (lysogeny). This choice is often informed by the cells state and by the number of infecting phage particles, or multiplicity of infection (MOI). Because the copy numbers of all phage genes scale identically with MOI, an MOI-dependent decision requires a rapidly established asymmetry between the lytic and lysogenic pathways. We introduce a minimal model showing how a simple coupling to host machinery (e.g. a protease) can generate such an asymmetry. Our analytical model yields scaling laws that predict how the lysislysogeny decision responds to perturbations of the host. It also quantitatively predicts stochastic features of infection outcomes, such as lysogeny probabilities, consistent with experimental data. By reducing complex regulatory networks to their essential components, our framework reveals the organizing principles of lysislysogeny decisions across phage species.