The "Goldilocks" Point for the Emergence of Antibiotic Resistance in Spatial Bacterial Populations

Low antibiotic concentration in a microenvironment allows for a large bacterial population, facilitating the emergence of a resistant mutant. It also implies a low fitness advantage for the mutant over the wild type which impedes mutant fixation. Using computer simulations to investigate the emergence of antibiotic resistance amidst a linear antibiotic gradient in one- and two-dimensional geometries, we found that the mutant fixed at higher antibiotic concentrations on increasing the rate of bacterial movement between microenvironments up to a threshold, beyond which the mutants had a higher chance of fixing at low antibiotic concentrations. The mechanism of mutant fixation was different on the two sides of the threshold and we describe a theory for the two scenarios. Dynamics in the one- and two-dimensional cases were qualitatively similar, with a higher rate of mutant fixation in the two-dimensional case. The results indicated that a trade-off between wild type population size and fitness advantage of the mutant governs the emergence of antibiotic resistance in spatial bacterial populations, and this “goldilocks” point for mutant fixation exhibits non-trivial dependence on the movement rate of the bacteria.