Authors: Lluís Hernández-Navarro, Kenneth Distefano, Uwe C. Täuber, and Mauro Mobilia.
We have published a new preprint!
You can find it on bioRxiv (https://doi.org/10.1101/2024.12.30.630406) and arXiv (https://doi.org/10.48550/arXiv.2501.01939). Supplementary data, codes, and movies are available on https://doi.org/10.17605/OSF.IO/EPB28.
See below for a brief description of the manuscript with a few illustrative figures. The full abstract is attached at the end.
1) Antimicrobial resistance (AMR) is a global threat and combating its spread is of paramount importance. AMR often results from resistant microbes sharing protection against drugs, and microbial communities generally evolve in volatile environments and spatial structures. This has a critical impact on AMR that has been understudied due to its complexity. Here we study a mixed population model of drug-sensitive and drug-resistant microbes on a surface (2D grid of demes). Microbes are exposed to an antimicrobial drug, undergo random births and deaths, and can migrate across the surface, while the environment switches back and forth between different levels of resources.
2) Sensitive and resistant microbes coexist for a long time in environments with constant nutrient levels. However, this picture changes dramatically when the environmental level of resources switches neither too rarely nor too often. Microbes then undergo consecutive population bottlenecks that cause random local extinctions of the resistant strain. Fast microbial migration rescues AMR, whereas strong environmental changes help eradicate AMR across the surface (see supplementary movie 3 on https://osf.io/xf2kp).
3) For these `intermediate-switching’ environments, we demonstrate that slow but nonzero cellular migration speeds up the clearance of AMR (see supplementary movies 1 and 2 on https://osf.io/jwpu2 and https://osf.io/w5qac). Through simulations and mathematical analysis, we determine the environmental conditions and cellular migration speeds that are optimal to eradicate AMR. These findings pave the way to innovative treatment options to prevent the spread of AMR in clinical and other applications.
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 non-zero migration speeds up the clearance of resistance and can enhance its eradication probability. We discuss our study’s impact on laboratory-controlled experiments.