Data from: Compensatory mutations improve general permissiveness to antibiotic resistance plasmids

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 multi-drug resistance plasmid RP4, determined plasmid persistence and cost using a joint experimental-modeling 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.

由宽宿主范围质粒（broad-host-range plasmids）介导的水平基因转移，是抗生素抗性传播的重要机制。尽管并非所有细菌都能同等程度地维持质粒，但质粒持久性（plasmid persistence）可随时间推移而提升，然而目前尚未发现普适性的进化机制。本研究旨在明确这类机制，并评估针对一种质粒的适应性是否会影响宿主对其他质粒的容许性（permissiveness）。我们对携带多重耐药质粒RP4（multi-drug resistance plasmid RP4）的假单胞菌属H2菌株（Pseudomonas sp. H2）开展了实验进化研究，采用实验与建模联合的方法测定了质粒持久性及其适合度代价（fitness cost），对进化获得的克隆株进行了重测序，并重构了关键突变位点。质粒持久性在不到600代的时间内便得到提升，这是因为原本的适合度代价转化为了适应性优势。宿主对未接触质粒（naive plasmids）的留存能力提升表明，其朝着更高的质粒容许性方向进化。关键的染色体突变涉及两种辅助解旋酶（accessory helicases）以及RNA聚合酶β亚基（RNA polymerase β-subunit）。本研究与其他同类研究的结果均表明，质粒持久性低下可能源于解旋酶-质粒互作所带来的高适合度代价，而这类代价可被快速缓解。