The evolution of multidrug antibiotic resistance in commensal bacteria is an important public health concern. Commensal bacteria such as Escherichia coli, Streptococcus pneumoniae or Staphylococcus aureus, are also opportunistic pathogens causing a large fraction of the community-acquired and hospital-acquired bacterial infections. Multidrug resistance (MDR) makes these infections harder to treat with antibiotics and may thus cause substantial additional morbidity and mortality. Here, we develop an evolutionary epidemiology model to identify the factors favouring the evolution of MDR in commensal bacteria. The model describes the evolution of antibiotic resistance in a commensal bacterial species evolving in a host population subjected to multiple antibiotic treatments. We combine statistical analysis of a large number of simulations and mathematical analysis to understand the model behaviour. We find that MDR evolves more readily when it is less costly than expected from the combinations of single resistances (positive epistasis). MDR frequently evolves when bacteria are in contact with multiple drugs prescribed in the host population, even if individual hosts are only treated with a single drug at a time. MDR is favoured when the host population is structured in different classes that vary in their rates of antibiotic treatment. However, under most circumstances, recombination between loci involved in resistance does not meaningfully affect the equilibrium frequency of MDR. Together, these results suggest that MDR is a frequent evolutionary outcome in commensal bacteria that encounter the variety of antibiotics prescribed in the host population. A better characterization of the variability in antibiotic use across the host population (e.g. across age classes or geographical location) would help predict which MDR genotypes will most readily evolve.

中文翻译：

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有利于细菌多药耐药性进化的因素

共生细菌中多药抗生素耐药性的演变是一个重要的公共卫生问题。共生细菌，如大肠杆菌、肺炎链球菌或金黄色葡萄球菌，也是造成大部分社区获得性和医院获得性细菌感染的机会性病原体。多药耐药性 (MDR) 使这些感染更难用抗生素治疗，因此可能导致大量额外的发病率和死亡率。在这里，我们开发了一个进化流行病学模型来确定有利于共生细菌 MDR 进化的因素。该模型描述了在接受多种抗生素治疗的宿主种群中进化的共生细菌物种中抗生素耐药性的进化。我们结合大量模拟的统计分析和数学分析来了解模型行为。我们发现，当 MDR 的成本低于单一抗性组合（阳性上位性）的预期成本时，它更容易进化。当细菌与宿主群体中规定的多种药物接触时，MDR 经常发生，即使单个宿主一次只接受一种药物治疗。当宿主群体分为不同类别且抗生素治疗率不同时，MDR 是有利的。然而，在大多数情况下，参与抗性的基因座之间的重组不会对 MDR 的平衡频率产生有意义的影响。一起，这些结果表明，在遇到宿主群体中规定的各种抗生素的共生细菌中，MDR 是一种常见的进化结果。更好地表征宿主人群中抗生素使用的变异性（例如跨年龄组或地理位置）将有助于预测哪些 MDR 基因型最容易进化。