Increased copy number couples the evolution of plasmid horizontal transmission and plasmid-encoded antibiotic resistance
Increased copy number couples the evolution of plasmid horizontal transmission and plasmid-encoded antibiotic resistance
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DOI：
10.1073/pnas.2107818118
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发表时间：
2021-08-03
影响因子：
11.1
通讯作者：
Buckling, Angus
中科院分区：
文献类型：
--
作者：
Dimitriu, Tatiana;Matthews, Andrew C.;Buckling, Angus
接合质粒是在细菌宿主之间水平分布的可移动元件，通常赋予适应性表型，包括抗菌素耐药性(AMR)。理论表明，水平传播的机会有利于具有较高转移率的质粒，而选择携带质粒则有利于流动性较低的质粒。然而，关于导致天然质粒传播率变化的机制或由此对其细菌宿主的影响，人们知之甚少。我们研究了不同易感宿主迁移率下AMR质粒的进化。质粒Rp4没有对这些操作做出反应，但在敏感宿主存在的情况下，质粒R1迅速进化到1000倍的转移率。大多数进化出的质粒还赋予宿主在高浓度抗生素下生长的能力。这是因为Plas-mids由于控制质粒复制的CopA基因突变而进化出更多的拷贝数，从而导致更高的转移率和AMR。反过来，当选择高水平的AMR时，尽管没有敏感宿主，但接合率增加的质粒也得到了进化。这种在质粒转移和AMR之间的相关性选择可能会增加AMR在种群和社区内的传播。
Conjugative plasmids are mobile elements that spread horizon-tally between bacterial hosts and often confer adaptive pheno-types, including antimicrobial resistance (AMR). Theory suggests that opportunities for horizontal transmission favor plasmids with higher transfer rates, whereas selection for plasmid carriage favors less-mobile plasmids. However, little is known about the mecha-nisms leading to variation in transmission rates in natural plasmids or the resultant effects on their bacterial host. We investigated the evolution of AMR plasmids confronted with different immigration rates of susceptible hosts. Plasmid RP4 did not evolve in response to the manipulations, but plasmid R1 rapidly evolved up to 1,000 -fold increased transfer rates in the presence of susceptible hosts. Most evolved plasmids also conferred on their hosts the ability to grow at high concentrations of antibiotics. This was because plas-mids evolved greater copy numbers as a function of mutations in the copA gene controlling plasmid replication, causing both higher transfer rates and AMR. Reciprocally, plasmids with increased con-jugation rates also evolved when selecting for high levels of AMR, despite the absence of susceptible hosts. Such correlated selection between plasmid transfer and AMR could increase the spread of AMR within populations and communities.