On the Ecological Significance of Phenotypic Heterogeneity in Microbial Populations Undergoing Starvation.

To persist in variable environments, populations of microorganisms have to survive periods of starvation and be able to restart cell division in nutrient-rich conditions. Typically, starvation signals initiate a transition to a quiescent state in a fraction of individual cells, while the rest of the cells remain nonquiescent. It is widely believed that, while quiescent (Q) cells help the population to survive long starvation, the nonquiescent (NQ) cells are a side effect of imperfect transition. We analyzed the regrowth of starved monocultures of Q and NQ cells compared to that of mixed, heterogeneous cultures from simple and complex starvation environments. Our experiments, as well as mathematical modeling, demonstrate that Q monocultures benefit from better survival during long starvation and from a shorter lag phase after resupply of rich medium. However, when the starvation period is very short, the NQ monocultures outperform Q and mixed cultures due to their short lag phase. In addition, only NQ monocultures benefit from complex starvation environments, where nutrient recycling is possible. Our study suggests that phenotypic heterogeneity in starved populations could be a form of bet hedging that is adaptive when environmental determinants, such as the length of the starvation period, the length of the regrowth phase, and the complexity of the starvation environment, vary over time.