Okamoto Kenichi W, Post David M, Vasseur David A, Turner Paul E
Department of Ecology and Evolutionary Biology Yale University New Haven Connecticut.
Department of Biology University of St. Thomas Saint Paul Minnesota.
Evol Appl. 2018 Sep 26;11(10):1822-1841. doi: 10.1111/eva.12683. eCollection 2018 Dec.
From agriculture to public health to civil engineering, managing antimicrobial resistance presents a considerable challenge. The dynamics underlying resistance evolution reflect inherently spatial processes. Resistant pathogen strains increase in frequency when a strain that emerges in one locale can spread and replace pathogen subpopulations formerly sensitive to the antimicrobial agent. Moreover, the strength of selection for antimicrobial resistance is in part governed by the extent of antimicrobial use. Thus, altering how antimicrobials are used across a landscape can potentially shift the spatial context governing the dynamics of antimicrobial resistance and provide a potent management tool. Here, we model how the efficacy of adjusting antimicrobial use over space to manage antimicrobial resistance is mediated by competition among pathogen strains and the topology of pathogen metapopulations. For several pathogen migration scenarios, we derive critical thresholds for the spatial extent of antimicrobial use below which resistance cannot emerge, and relate these thresholds to (a) the ability to eradicate antimicrobial-sensitive pathogens locally and (b) the strength of the trade-off between resistance ability and competitive performance where antimicrobial use is absent. We find that in metapopulations where patches differ in connectedness, constraining antimicrobial use across space to mitigate resistance evolution only works if the migration of the resistant pathogen is modest; yet, this situation is reversed if the resistant strain has a high colonization rate, with variably connected metapopulations exhibiting less sensitivity to reducing antimicrobial use across space. Furthermore, when pathogens are alternately exposed to sites with and without the antimicrobial, bottlenecking resistant strains through sites without an antimicrobial is only likely to be effective under a strong competition-resistance trade-off. We therefore identify life-history constraints that are likely to suggest which pathogens can most effectively be controlled by a spatially targeted antimicrobial regime. We discuss implications of our results for managing and thinking about antimicrobial resistance evolution in spatially heterogeneous contexts.
从农业到公共卫生再到土木工程，应对抗菌药物耐药性都面临着巨大挑战。耐药性演变背后的动态过程反映了内在的空间过程。当在一个地方出现的耐药病原体菌株能够传播并取代以前对抗菌药物敏感的病原体亚群时，其频率就会增加。此外，对抗菌药物耐药性的选择强度部分取决于抗菌药物的使用程度。因此，改变抗菌药物在整个区域的使用方式可能会改变控制抗菌药物耐药性动态的空间环境，并提供一种有效的管理工具。在这里，我们建立模型，研究通过病原体菌株之间的竞争和病原体集合种群的拓扑结构，空间上调整抗菌药物使用以控制抗菌药物耐药性的效果是如何介导的。对于几种病原体迁移情况，我们得出了抗菌药物使用空间范围的关键阈值，低于该阈值耐药性就不会出现，并将这些阈值与（a）在局部根除对抗菌药物敏感病原体的能力以及（b）在不使用抗菌药物的情况下耐药能力与竞争性能之间权衡的强度联系起来。我们发现，在斑块连通性不同的集合种群中，限制空间上的抗菌药物使用以减轻耐药性演变只有在耐药病原体迁移适度的情况下才有效；然而，如果耐药菌株的定殖率很高，情况则相反，连通性可变的集合种群对减少空间上的抗菌药物使用表现出较低的敏感性。此外，当病原体交替暴露于有抗菌药物和没有抗菌药物的地点时，只有在强大的竞争 - 耐药性权衡下，通过没有抗菌药物的地点限制耐药菌株才可能有效。因此，我们确定了可能表明哪些病原体可以通过空间靶向抗菌药物方案最有效地得到控制的生活史限制因素。我们讨论了我们的结果对于在空间异质环境中管理和思考抗菌药物耐药性演变的意义。
