Ecological effects of stress drive bacterial evolvability under sub-inhibitory antibiotic treatments

Abstract Stress is thought to increase mutation rate and thus to accelerate evolution. In the context of antibiotic resistance, sub-inhibitory treatments could then lead to enhanced evolvability, thereby fuelling the adaptation of pathogens. Combining wet-lab experiments, stochastic simulations and a meta-analysis of the literature, we found that the increase in mutation rates triggered by antibiotic treatments is often cancelled out by reduced population size, resulting in no overall increase in genetic diversity. A careful analysis of the effect of ecological factors on genetic diversity showed that the potential for regrowth during recovery phase after treatment plays a crucial role in evolvability, being the main factor associated with increased genetic diversity in experimental data.