The art of being sloppy: stochasticity as an evolutionary trait in phage populations*

The life history parameters of lytic phages is typically summarized by three quantities -adsorption rate, lysis time and bust size, which are traditionally measured as bulk averages from liquid culture experiments. Directed evolution experiments in different bacterial conditions have been shown to select for different optimal sets of these parameters in qualitative agreement with predictions from simple models of phage infection. In a variation of such experiments, we have recently evolved lines of phage T7 that spread 5 times faster than the ancestor on two-dimensional bacterial lawns. Surprisingly, in contrast to model expectations and previous similar experiments that predict a decrease in adsorption rate, our evolved lines fail to show any significant or consistent change in life history parameters bringing into questions both the assumptions underneath current models and the experimental methods we use to assess phage-bacteria interactions.

In an attempt to provide and test a hypothesis for our surprising experiment, I will present simulation results revealing that a slightly wider distribution of lysis time can confer significant fitness advantage to a phage population, while going undetected in traditional phenotypic assays. To bypass this problem and precisely quantify the amount of stochasticity in phage-bacteria interactions, I will introduce a novel platform that leverages phage synthetic engineering and mother-machine microfluidic experiments to monitor phage infection dynamics at single-cell resolution over thousands of cells simultaneously. Our approach reveals some insight into how phage can take advantage of cell-to-cell variability to increase noise in the infection dynamics and maximize its chances to evolutionary success.