Zwanzig Martin, Harrison Ellie, Brockhurst Michael A, Hall James P J, Berendonk Thomas U, Berger Uta
Department of Forest Sciences, Institute of Forest Growth and Forest Computer Science, Technische Universität Dresden, Tharandt, Germany.
Department of Animal and Plant Sciences, University of Sheffield, Sheffield, United Kingdom.
mSystems. 2019 Jan 15;4(1). doi: 10.1128/mSystems.00186-18. eCollection 2019 Jan-Feb.
The global dissemination of plasmids encoding antibiotic resistance represents an urgent issue for human health and society. While the fitness costs for host cells associated with plasmid acquisition are expected to limit plasmid dissemination in the absence of positive selection of plasmid traits, compensatory evolution can reduce this burden. Experimental data suggest that compensatory mutations can be located on either the chromosome or the plasmid, and these are likely to have contrasting effects on plasmid dynamics. Whereas chromosomal mutations are inherited vertically through bacterial fission, plasmid mutations can be inherited both vertically and horizontally and potentially reduce the initial cost of the plasmid in new host cells. Here we show using mathematical models and simulations that the dynamics of plasmids depends critically on the genomic location of the compensatory mutation. We demonstrate that plasmid-located compensatory evolution is better at enhancing plasmid persistence, even when its effects are smaller than those provided by chromosomal compensation. Moreover, either type of compensatory evolution facilitates the survival of resistance plasmids at low drug concentrations. These insights contribute to an improved understanding of the conditions and mechanisms driving the spread and the evolution of antibiotic resistance plasmids. Understanding the evolutionary forces that maintain antibiotic resistance genes in a population, especially when antibiotics are not used, is an important problem for human health and society. The most common platform for the dissemination of antibiotic resistance genes is conjugative plasmids. Experimental studies showed that mutations located on the plasmid or the bacterial chromosome can reduce the costs plasmids impose on their hosts, resulting in antibiotic resistance plasmids being maintained even in the absence of antibiotics. While chromosomal mutations are only vertically inherited by the daughter cells, plasmid mutations are also provided to bacteria that acquire the plasmid through conjugation. Here we demonstrate how the mode of inheritance of a compensatory mutation crucially influences the ability of plasmids to spread and persist in a bacterial population.
编码抗生素抗性的质粒在全球范围内传播，这对人类健康和社会来说是一个紧迫问题。虽然在没有质粒性状正向选择的情况下，与获得质粒相关的宿主细胞适应性代价预计会限制质粒传播，但补偿性进化可以减轻这种负担。实验数据表明，补偿性突变可能位于染色体或质粒上，而这些突变可能对质粒动态产生不同影响。染色体突变通过细菌分裂垂直遗传，而质粒突变既可以垂直遗传也可以水平遗传，并且可能降低质粒在新宿主细胞中的初始代价。在这里，我们使用数学模型和模拟表明，质粒的动态在很大程度上取决于补偿性突变的基因组位置。我们证明，即使质粒上的补偿性进化的影响小于染色体补偿所提供的影响，它在增强质粒持久性方面也更有效。此外，任何一种类型的补偿性进化都有助于抗性质粒在低药物浓度下存活。这些见解有助于更好地理解驱动抗生素抗性质粒传播和进化的条件及机制。了解在群体中维持抗生素抗性基因的进化力量，尤其是在不使用抗生素时，对人类健康和社会来说是一个重要问题。抗生素抗性基因传播的最常见载体是接合性质粒。实验研究表明，位于质粒或细菌染色体上的突变可以降低质粒对其宿主施加的代价，从而即使在没有抗生素的情况下也能维持抗生素抗性质粒。虽然染色体突变仅由子细胞垂直遗传，但质粒突变也会传递给通过接合获得质粒的细菌。在这里，我们展示了补偿性突变的遗传模式如何关键地影响质粒在细菌群体中传播和持续存在的能力。
