The Emergence, Maintenance and Demise of Diversity in a Spatially Variable Antibiotic Regime

Abstract

Antimicrobial resistance is a serious and imminent threat to human health, though its rise may be controlled with improved stewardship strategies that limit the emergence and spread of resistant strains. Motivated by theoretical models from population genetics and ecology, my M.Sc. experimentally evaluates how varying drug availability in either time or space impacts the prevalence of resistance in a population. By experimentally evolving Pseudomonas aeruginosa under different antibiotic selection regimes in vitro, I show that spatial, but not temporal, drug free refuges delay the fixation of resistance by promoting the coexistence of sensitive and resistant genotypes. Second, I establish that this polymorphism is underlain by a trade-off between resistance and growth rate in the absence of antibiotic that underpins the maintenance of diversity through negative frequency dependent selection. Third, I demonstrate that spatially varied drug selection cannot prevent the fixation of resistance because continued selection leads to the evolution of resistant types that pay smaller costs of resistance and gradually displace sensitive strains. These results provide insight into the fate of diversity under long-term selection and highlight the value of incorporating the principles of evolutionary ecology into antimicrobial resistance stewardship.