Efficiency is better than speed for competitive suppression of drug resistance

Antimicrobial resistance (AMR) is a growing threat to human health, agriculture, and natural ecosystems. While antimicrobial use is a primary driver of resistance evolution, growing evidence suggests that anthropogenic environmental change may also contribute to the emergence and spread of resistant microbes. Yet the mechanisms linking environmental conditions to AMR remain poorly understood and are largely absent from current strategies to manage resistance. This gap arises, in part, because we still know surprisingly little about how ecological interactions shape the evolutionary dynamics of antimicrobial resistance. Here, we develop a general eco-evolutionary modeling framework to investigate how spatial structure, resource availability, and growth-efficiency trade-offs shape competition between drug-sensitive and drug-resistant strains. We show that spatial heterogeneity influences resistance evolution not simply by strengthening or weakening competition, but by altering the ecological mechanisms through which competition suppresses resistant strains. In homogeneous environments, resistance is suppressed primarily by faster-growing drug-sensitive competitors and only under a relatively narrow range of ecological conditions. In contrast, heterogeneous environments with limited resources favor more resource-efficient drug-sensitive strains, which outcompete resistant strains through a distinct colonization advantage that operates across a broader region of parameter space. These patterns emerge regardless of whether resistant mutants are initially present or arise de novo through mutation. Together, our results provide insight into mechanistic links between environmental change and AMR emergence, suggesting that environmental homogenization and resource enrichment may reduce opportunities for competitive suppression and thereby increase resistance risk. More broadly, this work demonstrates how ecological interactions and environmental structure shape the evolution of resistance and offers possible insight into resistance management.