Data from: The genetic basis of the fitness costs of antimicrobial resistance: a meta-analysis approach

The evolution of antibiotic resistance carries a fitness cost, expressed in terms of reduced competitive ability in the absence of antibiotics. This cost plays a key role in the dynamics of resistance by generating selection against resistance when bacteria encounter an antibiotic-free environment. Previous work has shown that the cost of resistance is highly variable, but the underlying causes remain poorly understood. Here, we use a meta-analysis of the published resistance literature to determine how the genetic basis of resistance influences its cost. We find that on average chromosomal resistance mutations carry a larger cost than acquiring resistance via a plasmid. This may explain why resistance often evolves by plasmid acquisition. Second, we find that the cost of plasmid acquisition increases with the breadth of its resistance range. This suggests a potentially important limit on the evolution of extensive multidrug resistance via plasmids. We also find that epistasis can significantly alter the cost of mutational resistance. Overall, our study shows that the cost of antimicrobial resistance can be partially explained by its genetic basis. It also highlights both the danger associated with plasmidborne resistance and the need to understand why resistance plasmids carry a relatively low cost.

抗生素耐药性的演化伴随适应成本，具体体现为无抗生素环境下竞争能力的降低。当细菌接触无抗生素环境时，该成本会催生针对耐药性的选择压，在耐药性的动态变化中发挥关键作用。既往研究显示，耐药性的适应成本存在高度变异，但其背后的成因仍未得到充分阐释。在此，我们针对已发表的耐药性相关文献开展荟萃分析（meta-analysis），以明确耐药性的遗传基础如何影响其适应成本。我们发现，相较于通过质粒获取耐药性，染色体耐药突变平均带来的适应成本更高；这一结果或可解释为何耐药性演化常通过质粒获取途径发生。其次，我们发现质粒获取耐药性的成本随其耐药谱广度的增加而升高，这提示质粒介导的广泛多重耐药性演化可能存在潜在的重要限制。此外，我们还发现上位性（epistasis）可显著改变突变耐药性的适应成本。总体而言，本研究表明抗菌药物耐药性的成本可部分通过其遗传基础得到解释；同时，本研究也凸显了质粒介导耐药性的潜在危害，以及阐明耐药质粒为何携带相对较低适应成本的必要性。