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 multi-drug 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 plasmid-borne 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着适合度代价，表现为在无抗生素环境下细菌的竞争能力下降。当细菌处于无抗生素环境时，该代价会通过产生针对耐药性的负选择，在耐药性的动态变化中发挥关键作用。既往研究表明，耐药性的适合度代价存在高度异质性，但目前其潜在成因仍未被充分阐明。为此，我们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合度代价。我们发现，平均而言，染色体耐药突变所带来的适合度代价，高于通过获取质粒（plasmid）获得耐药性所对应的代价。这或可解释为何耐药性的演化常通过获取质粒的方式实现。其次，我们发现，获取质粒所带来的适合度代价会随其耐药谱的拓宽而升高，这表明通过质粒演化出广泛多重耐药性的过程可能存在重要限制。我们还发现，上位性（epistasis）能够显著改变突变耐药性的适合度代价。总体而言，本研究表明，抗菌药物耐药性的适合度代价可部分通过其遗传基础得到解释；本研究同时凸显了质粒携带耐药性所带来的潜在风险，以及阐明耐药质粒为何仅伴随较低适合度代价的必要性。