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

TL;DR

This study explores how slow spatial migration in fluctuating environments can effectively eradicate cooperative antimicrobial resistance by balancing migration and environmental variability, providing insights for controlling resistance spread.

Contribution

It reveals that slow, nonzero migration can accelerate resistance clearance in time-varying spatial environments, a novel insight into AMR management strategies.

Findings

Slow migration speeds up resistance eradication.

Environmental fluctuations influence resistance dynamics.

Optimal conditions exist for resistance clearance.

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 drug protection. Microbial communities generally evolve in volatile, spatially structured settings. Migration, space, fluctuations, and environmental variability all have a significant impact on the development and proliferation of AMR. While drug resistance is enhanced by migration in static conditions, this changes in time-fluctuating spatially structured environments. Here, we consider a two-dimensional metapopulation consisting of demes in which drug-resistant and sensitive cells evolve in a time-changing environment. This contains a toxin against which protection can be shared (cooperative AMR). Cells migrate between demes and connect them. When the environment and the deme composition vary on the same timescale, strong population bottlenecks cause fluctuation-driven extinction events, countered by migration. We investigate the influence of migration and environmental variability on the AMR eco-evolutionary dynamics by asking at what migration rate fluctuations can help clear resistance and what are the near-optimal environmental conditions ensuring the quasi-certain eradication of resistance in the shortest possible time. By combining analytical and computational tools, we answer these questions by determining when the resistant strain goes extinct across the entire metapopulation. While dispersal generally promotes strain coexistence, here we show that slow-but-nonzero migration can speed up and enhance resistance clearance, and determine the near-optimal conditions for this phenomenon. We discuss the impact of our findings on laboratory-controlled experiments and outline their generalisation to lattices of any spatial dimension.