Triggered and Spontaneous Dormancy in Bacteria During Feast-Famine Cycles with Stochastic Antibiotic Application

Abstract

Bacteria can enter dormancy triggered by stress, such as starvation. When stress is removed, a large part of the population will exhibit some lag time before regrowth. It has been observed that even under stress-free conditions that allow for exponential growth, a small subpopulation can spontaneously enter dormancy temporarily. The dormant population often survives antibiotic application because many types of antibiotics target the cell growth and division process. If bacteria are in an environment where antibiotics are sometimes applied, the population can evolve to adjust their dormancy frequency to better survive antibiotics without losing too much of the population growth. Here, we consider the situation in which antibiotics are applied stochastically during repeated feast-famine cycles. We analyse the best strategy for long-term growth when the bacteria are allowed to tune both the lag time at the start of the feast period and the spontaneous dormancy in the feast period. We show that spontaneous dormancy can provide an advantage only when the antibiotic application and the start of the feast period are decoupled. When the triggered dormant and spontaneous dormant states are treated as different states and the antibiotic addition time is fixed, the optimal strategy is either triggered or spontaneous dormancy. Exhibiting both types of dormancy is optimal only when there is a certain level of stochastic fluctuation in the antibiotic application timing.