Bacterial motility governs the evolution of antibiotic resistance in spatially heterogeneous environments

Abstract

Bacteria evolving in natural and clinical settings experience spatial fluctuations of multiple factors and this heterogeneity is expected to affect bacterial adaptation. Notably, spatial heterogeneity in antibiotic concentrations is believed to accelerate the evolution of antibiotic resistance. However, current literature overlooks the role of cell motility, which is key for bacterial survival and reproduction. Here, we consider a quantitative model for bacterial evolution in antibiotic gradients, where bacteria evolve under the stochastic processes of proliferation, death, mutation and migration. Numerical and analytical results show that cell motility has major effects on bacterial adaptation. If migration is relatively rare, it accelerates adaptation because resistant mutants can colonize neighbouring patches of increasing antibiotic concentration avoiding competition with wild-type cells; but if migration is common throughout the lifespan of bacteria, it decelerates adaptation by promoting genotypic mixing and ecological competition. If migration is sufficiently high, it can limit bacterial survival, and we derive conditions for such a regime. Similar patterns are observed in more complex scenarios, namely where bacteria can bias their motion or switch between motility phenotypes either stochastically or in a density-dependent manner. Overall, our work reveals limits to bacterial adaptation in antibiotic landscapes that are set by cell motility.