Spatial structure facilitates evolutionary rescue by cost-free drug resistance

Cecilia Fruet, Ella Linxia Müller, Claude Loverdo, Anne-Florence Bitbol
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Abstract

Bacterial populations often have complex spatial structures, which can impact their evolution. Here, we study how spatial structure affects the evolution of antibiotic resistance in a bacterial population. We consider a minimal model of spatially structured populations where all demes (i.e., subpopulations) are identical and connected to each other by identical migration rates. We show that spatial structure can facilitate the survival of a bacterial population to antibiotic treatment, starting from a sensitive inoculum. Indeed, the bacterial population can be rescued if antibiotic resistant mutants appear and are present when drug is added, and spatial structure can impact the fate of these mutants and the probability that they are present. Specifically, if the mutation that provides resistance is neutral or effectively neutral, its probability of fixation is increased in smaller populations. This promotes local fixation of resistant mutants in the structured population, which facilitates evolutionary rescue by cost-free drug resistance. Once the population is rescued by resistance, migrations allow resistant mutants to spread in all demes. Our main results extend to the case where there are resistant mutants in the inoculum, and to more complex spatial structures. They also extend to resistant mutants that carry a fitness cost, although the timescales involved are longer.
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空间结构有利于无成本抗药性的进化救援
细菌种群通常具有复杂的空间结构,这会影响它们的进化。在此,我们将研究空间结构如何影响细菌种群中抗生素耐药性的进化。我们考虑了一个空间结构种群的最小模型,在这个模型中,所有的种群(即亚种群)都是相同的,并且通过相同的迁移率相互连接。我们的研究表明,从敏感的接种体开始,空间结构可以帮助细菌种群在抗生素治疗中存活下来。事实上,如果出现抗生素突变体并在添加药物时出现,细菌种群就能得到拯救,而空间结构会影响这些突变体的命运及其出现的概率。具体来说,如果提供抗药性的突变是中性或有效中性的,那么它在较小种群中固定的概率就会增加。这就促进了结构化种群中抗性突变体的局部固定,从而有利于通过无成本的抗药性进行进化拯救。一旦种群被抗药性拯救,迁移就会使抗药性突变体在所有种群中扩散。我们的主要结果可以扩展到接种体中存在抗药性突变体的情况,以及更复杂的空间结构。这些结果也适用于需要付出健康代价的抗性突变体,尽管所涉及的时间尺度更长。
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