Department of Biological Sciences, University of Idaho, PO Box 443051, Moscow, ID, 83844, USA.
Institute for Bioinformatics and Evolutionary Studies (IBEST), University of Idaho, PO Box 443051, Moscow, ID, 83844, USA.
Nat Ecol Evol. 2017 Sep;1(9):1354-1363. doi: 10.1038/s41559-017-0243-2. Epub 2017 Aug 7.
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.
水平基因转移由广泛宿主范围质粒介导是抗生素耐药性传播的一个重要机制。虽然并非所有细菌都能同等程度地维持质粒，但质粒的持久性可以随着时间的推移而提高，但尚未出现普遍的进化机制。我们的目标是确定这些机制，并评估对一种质粒的适应是否会影响对其他质粒的允许性。我们通过实验进化了含有多药耐药性质粒 RP4 的假单胞菌 H2，使用联合实验建模方法确定了质粒的持久性和代价，对进化后的克隆进行了重测序，并重建了关键突变。质粒的持久性在不到 600 代的时间内得到了改善，因为适应代价变成了好处。原始质粒的保留率提高表明宿主朝着增加质粒允许性的方向进化。关键的染色体突变影响了两个辅助解旋酶和 RNA 聚合酶 β 亚基。我们和其他研究结果表明，较差的质粒持久性可能是由于涉及解旋酶-质粒相互作用的高代价引起的，这种相互作用可以迅速得到改善。
