Growth-dependent drug susceptibility can prevent or enhance spatial expansion of a bacterial population

Abstract

As a population wave expands, organisms at the tip typically experience plentiful nutrients while those behind the front become nutrient-depleted. If the environment also contains a gradient of some inhibitor (e.g. a toxic drug), a tradeoff exists: the nutrient-rich tip is more exposed to the inhibitor, while the nutrient-starved region behind the front is less exposed. Here we show that this can lead to complex dynamics when the organism's response to the inhibitory substance is coupled to nutrient availability. We model a bacterial population which expands in a spatial gradient of antibiotic, under conditions where either fast-growing bacteria at the wave's tip, or slow-growing, resource-limited bacteria behind the front are more susceptible to the antibiotic. We find that growth-rate dependent susceptibility can have strong effects on the dynamics of the expanding population. If slow-growing bacteria are more susceptible, the population wave advances far into the inhibitory zone, leaving a trail of dead bacteria in its wake. In contrast, if fast-growing bacteria are more susceptible, the wave is blocked at a much lower concentration of antibiotic, but a large population of live bacteria remains behind the front. Our results may contribute to understanding the efficacy of different antimicrobials for spatially structured microbial populations such as biofilms, as well as the dynamics of ecological population expansions more generally.