Single-cell imaging of the lytic phage life cycle dissects the timing and noise in individual infection steps

Abstract

When a lytic bacteriophage infects a bacterial cell, it commandeers the cells resources to replicate, ultimately causing cell lysis and the release of new virions. As phages function as 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 timelapse 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 with different lysis time distributions reveal that heterogeneity in infection dynamics can significantly impact phage fitness, highlighting it as a potential evolutionary driver of phage-bacteria interactions.