Uncoupling the effects of host cell size and growth rate on phage infection dynamics

Bacteriophages are dependent on their bacterial host to replicate. Previous studies have shown that phage adsorption, lysis time, and burst size are all highly sensitive to host growth conditions. However, these studies mainly focus on bacterial growth on different carbon sources, which leads to confounding effects in host cell geometry and growth rate. To disentangle bacterial size effects from growth rate, we investigate Lambda cI857 lytic phage infection dynamics across E. coli strains from an mreB mutant library that spans different cell geometries with minimal changes in growth rate. We find that host cell width is highly correlated to the speed of infection in batch culture with identical starting phage titers, indicating that phage infection parameters are inherently sensitive to cell geometry. Using physiology-informed mathematical modeling, we generate hypotheses for how host volume and membrane surface area impact individual infection parameters and test our models by measuring each parameter across mutant strains. Overall, this study provides new mechanistic insights into host-phage interdependencies and phage infection dynamics beyond the genetic level.