Emerging patterns of plasmid-host coevolution that stabilize antibiotic resistance.

Emerging patterns of plasmid-host coevolution that stabilize antibiotic resistance.
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DOI:
10.1038/s41598-017-04662-0
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发表时间:
2017-07-07
期刊:
影响因子:
4.6
通讯作者:
Top EM
Top EM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Stalder T;Rogers LM;Renfrow C;Yano H;Smith Z;Top EM

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多重耐药细菌病原体已成为严重的全球人类健康威胁,接合质粒是对最后手段抗生素的耐药性迅速传播的重要驱动因素。虽然抗生素已经显示出选择抗性质粒适应其新的细菌宿主,反之亦然,但一般的进化机制尚未出现。在这里,我们进行了实验进化研究,旨在确定质粒细菌进化的一般模式。具体来说,我们发现,一个大的接合抗性质粒遵循相同的进化轨迹,其非接合迷你复制子在相同和其他物种。此外,在单个宿主-质粒对内,三种不同的适应性进化模式导致质粒持久性增加:i)复制蛋白基因(trfA 1)中的突变; ii)抗性质粒从编码推定的毒素-抗毒素系统的共存质粒获得转座子; iii)宿主的全局转录调节基因fur中的突变。由于这些进化的解决方案中的每一个单独地已被证明可以增加质粒在其他质粒-宿主对中的持久性,因此我们的工作指向质粒稳定化的共同机制。这些可能成为未来替代药物疗法的目标,以减缓抗生素耐药性的传播。
Multidrug resistant bacterial pathogens have become a serious global human health threat, and conjugative plasmids are important drivers of the rapid spread of resistance to last-resort antibiotics. Whereas antibiotics have been shown to select for adaptation of resistance plasmids to their new bacterial hosts, or vice versa, a general evolutionary mechanism has not yet emerged. Here we conducted an experimental evolution study aimed at determining general patterns of plasmid-bacteria evolution. Specifically, we found that a large conjugative resistance plasmid follows the same evolutionary trajectories as its non-conjugative mini-replicon in the same and other species. Furthermore, within a single host–plasmid pair three distinct patterns of adaptive evolution led to increased plasmid persistence: i) mutations in the replication protein gene (trfA1); ii) the acquisition by the resistance plasmid of a transposon from a co-residing plasmid encoding a putative toxin-antitoxin system; iii) a mutation in the host’s global transcriptional regulator gene fur. Since each of these evolutionary solutions individually have been shown to increase plasmid persistence in other plasmid-host pairs, our work points towards common mechanisms of plasmid stabilization. These could become the targets of future alternative drug therapies to slow down the spread of antibiotic resistance.
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发表时间: 2003-06-01
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影响因子: 2
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影响因子: 5.5
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