Single-cell imaging of the lytic phage life cycle in bacteria

Upon infecting a bacterial cell, a lytic bacteriophage commandeers the host's resources to replicate, before lysing the cell to release new virions. As phages are obligate parasites, each stage of the infection process depends on the physiological parameters of the host cell. Given the inherent physiological variability within a population of genetically identical bacterial cells, we ask how the phage infection dynamic reflects such heterogeneity. Here, we introduce a time-lapse imaging assay for investigating the dynamics of individual infection steps by a single T7 phage on a single bacterium. This high-throughput, time-resolved assay enables us to monitor the infection progression simultaneously in multiple cells, uncovering substantial heterogeneity at each step and revealing correlations between infection dynamics and the physiological state of the infected cell. Simulations of competing phage populations reveal that heterogeneity in infection dynamics can significantly impact phage fitness, highlighting it as a potential evolutionary driver of phage-bacteria interactions. A record of this paper's transparent peer review process is included in the supplemental information.