Slow spatial migration can help eradicate cooperative antimicrobial resistance in time-varying environments

Abstract

Antimicrobial resistance (AMR) is a global threat and combating its spread is of paramount importance. AMR often results from a cooperative behaviour with shared protection against drugs. Microbial communities generally evolve in volatile environments and spatial structures. Migration, fluctuations, and environmental variability thus have significant impacts on AMR, whose maintenance in static environments is generally promoted by migration. Here, we demonstrate that this picture changes dramatically in time-fluctuating spatially structured environments. To this end, we consider a two-dimensional metapopulation model consisting of demes in which drug-resistant and sensitive cells evolve in a time-changing environment in the presence of a toxin against which protection can be shared. Cells migrate between neighbouring demes and hence connect them. When the environment varies neither too quickly nor too slowly, the dynamics is characterised by bottlenecks causing fluctuation-driven local extinctions, a mechanism countered by migration that rescues AMR. Through simulations and mathematical analysis, we investigate how migration and environmental variability influence the probability of resistance eradication. We determine the near-optimal conditions for the fluctuation-driven AMR eradication, and show that slow but nonzero migration speeds up the clearance of resistance and can enhance its eradication probability. We discuss our study’s impact on laboratory-controlled experiments.