Timing is everything: regulation of bacterial defences and phage counter-defences

Gene regulation has emerged as an important determinant of phage infection outcomes. Host susceptibility and immunity are often governed by conditional gene expression, which allows reversible shifts in receptor availability and defence system activity that balance phage resistance with fitness costs. Phages likewise rely on tightly regulated gene expression, precisely timing counter-defence deployment and manipulating host transcriptional programmes as well as immune signalling pathways. These dynamics position gene regulation as a major determinant of bacteria-phage co-evolution, acting alongside the gain and loss of defence and counter-defence genes. Viewing phage-host interactions through gene regulation provides insight into variability in infection dynamics and helps explain why genomic information alone cannot accurately predict phage activity.