标题： 缓慢的空间迁移可以在时变环境中根除合作型抗菌素耐药性 显示英文标题

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

摘要： 抗菌素耐药性（AMR）是全球性的威胁，遏制其传播至关重要。 AMR通常源于一种共享药物保护的协作行为。 微生物群落一般在易变的环境中进化，并具有空间结构。 因此，迁移、波动和环境变异性对AMR有显著影响，在静态环境中，迁移通常会促进AMR的维持。 在这里，我们证明了这一情况在随时间波动的空间结构化环境中发生了巨大变化。 为此，我们考虑了一个二维的元种群模型，其中包含在存在毒素的情况下，在时变环境中演化的耐药细胞和敏感细胞的小种群。 细胞在邻近的小种群之间迁移并连接它们。 当环境变化既不太快也不太慢时，动力学由瓶颈引起，导致波动驱动的局部灭绝，这种机制通过迁移得以抵消，从而拯救了AMR。 通过模拟和数学分析，我们研究了迁移和环境变异性如何影响抗性清除的概率。 我们确定了波动驱动的抗性清除的近似最优条件，并表明缓慢但非零的迁移速度可以加快抗性的清除并提高其清除概率。 我们讨论了本研究对实验室控制实验的影响。 显示英文摘要

摘要： 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.