摘要

由广泛宿主范围质粒介导的水平基因转移是抗生素抗性传播的重要机制。虽然并非所有的细菌都能很好地保持质粒，但质粒持续性可随时间推移而改善，但尚未出现一般的进化机制。我们的目标是确定这些机制并评估对一个质粒的适应是否会影响其他人的宽容度。我们通过实验发展了假单胞菌sp。含有多药耐药质粒RP4的H2，使用联合实验建模方法测定质粒持续性和成本，重新测序进化克隆和重建的关键突变。由于适应成本转变为益处，质粒持续性在不到600代中改善。初始质粒保留的改善表明宿主进化为质粒允许性增加。关键染色体突变影响两个辅助解旋酶和RNA聚合酶β亚基。我们和其他研究结果表明，质粒持久性较差可能是由涉及解旋酶 - 质粒相互作用的高成本引起的，这些相互作用可以迅速得到改善。

Horizontal gene transfer mediated by broad-host-range plasmids is an important mechanism of antibiotic resistance spread. While not all bacteria maintain plasmids equally well, plasmid persistence can improve over time, yet no general evolutionary mechanisms have emerged. Our goal was to identify these mechanisms and to assess if adaptation to one plasmid affects the permissiveness to others. We experimentally evolved Pseudomonas sp. H2 containing multidrug resistance plasmid RP4, determined plasmid persistence and cost using a joint experimental–modelling approach, resequenced evolved clones, and reconstructed key mutations. Plasmid persistence improved in fewer than 600 generations because the fitness cost turned into a benefit. Improved retention of naive plasmids indicated that the host evolved towards increased plasmid permissiveness. Key chromosomal mutations affected two accessory helicases and the RNA polymerase β-subunit. Our and other findings suggest that poor plasmid persistence can be caused by a high cost involving helicase–plasmid interactions that can be rapidly ameliorated.

https://www.nature.com/articles/s41559-017-0243-2