In light of the escalating antibiotic resistance crisis it is crucial to understand how different antibiotic dosing schedules influence the evolution of resistance in microbial systems. While extensive research has focused on optimizing dosing regimes from a pharmacodynamic perspective, the ecological and evolutionary consequences of varying temporal patterns of antibiotic delivery, when paired with resource dynamics, have been largely overlooked.
Drawing on ecological theory and classical resource competition models, it has been shown that different temporal patterns of covariance between resource supply and antibiotic pulses can lead to different competitive outcomes between resistant and sensitive bacterial strains. Specifically, it is predicted that negative covariance, where resource pulses are out of phase with intermittent antibiotic pulses favours sensitive strains, thereby selecting against resistance. In contrast, positive covariance, where resource pulses coincide with antibiotic pulses can benefit resistant strains, promoting the evolution of resistance.
In this study, we empirically tested these model-based predictions using Escherichia coli as a model system. Specifically, we investigated how variation in the temporal covariance of bacteriostatic and bactericidal antibiotics with resource availability affects the evolution of resistance through laboratory evolution experiments. Using both classes of antibiotics allows for a comparative analysis of how these two classes of drugs influence evolutionary outcomes under different resource-antibiotic covariance scenarios. This study provides novel insights into the consequences of resource competition for the evolution of antibiotic resistance and may ultimately help the development of resistance-aware antibiotic dosing strategies.