Host-specific plasmid evolution explains the variable spread of clinical antibiotic-resistance plasmids.
Host-specific plasmid evolution explains the variable spread of clinical antibiotic-resistance plasmids.
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宿主特异性的质粒演化解释了临床抗生素抗性质粒的变化扩散。
DOI：
10.1073/pnas.2212147120
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发表时间：
2023-04-11
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
抗生素耐药性是治疗细菌感染的主要挑战。抗性基因通常位于称为质粒的可移动遗传元件上。能够预测哪种细菌-质粒组合最成功，包括在不使用抗生素的情况下，将有助于管理耐药性。我们使用临床细菌进行实验，显示影响质粒传播的关键参数在不同的细菌-质粒组合之间存在差异，但这不足以预测哪些组合从长远来看最成功。相反，考虑到质粒的快速进化，显着提高了我们解释哪种组合效果最好的能力，因为质粒进化关键取决于它们所携带的细菌宿主。考虑快速的、菌株特异性的质粒进化可能有助于预测和对抗耐药性。质粒上编码的抗生素耐药性是一个紧迫的全球健康问题。尽管已经确定了影响质粒稳定性的一些关键参数，例如质粒生长成本和水平转移率，但预测哪些质粒会长期传播仍然非常具有挑战性。在这里，我们展示了这些参数在临床质粒和细菌中以菌株特异性方式进化，并且这种变化发生得足够快，足以改变不同细菌-质粒组合传播的相对可能性。我们使用大肠杆菌和从患者身上分离的抗生素抗性质粒进行实验，并结合数学模型来跟踪长期质粒稳定性（超出抗生素暴露范围）。解释六种细菌-质粒组合的可变稳定性需要考虑质粒稳定性特征的进化变化，而这些参数的初始变化对于长期结果的预测相对较差。正如基因组测序和遗传操作所证明的那样，进化轨迹特定于特定的细菌-质粒组合。这揭示了影响水平质粒转移的关键遗传变化的上位（此处为菌株依赖性）效应。一些遗传变化涉及移动元件和致病岛。因此，快速的菌株特异性进化可以超过祖先表型作为质粒稳定性的预测因子。考虑自然群体中菌株特异性质粒的进化可以提高我们预测和管理成功的细菌-质粒组合的能力。
Antibiotic resistance is a major challenge in treating bacterial infections. Resistance genes are often on mobile genetic elements called plasmids. Being able to predict which bacterium–plasmid combinations are most successful, including in the absence of antibiotics, would help manage resistance. We used experiments with clinical bacteria to show key parameters affecting the spread of plasmids varied among different bacterium–plasmid combinations, but this was not sufficient to predict which combinations were most successful in the long term. Instead, accounting for rapid evolution of plasmids significantly advanced our ability to explain which combinations did best, because plasmid evolution depended critically on which bacterial host they were carried by. Accounting for rapid, strain-specific plasmid evolution may help predict and combat resistance. Antibiotic resistance encoded on plasmids is a pressing global health problem. Predicting which plasmids spread in the long term remains very challenging, even though some key parameters influencing plasmid stability have been identified, such as plasmid growth costs and horizontal transfer rates. Here, we show these parameters evolve in a strain-specific way among clinical plasmids and bacteria, and this occurs rapidly enough to alter the relative likelihoods of different bacterium–plasmid combinations spreading. We used experiments with Escherichia coli and antibiotic-resistance plasmids isolated from patients, paired with a mathematical model, to track long-term plasmid stability (beyond antibiotic exposure). Explaining variable stability across six bacterium–plasmid combinations required accounting for evolutionary changes in plasmid stability traits, whereas initial variation of these parameters was a relatively poor predictor of long-term outcomes. Evolutionary trajectories were specific to particular bacterium–plasmid combinations, as evidenced by genome sequencing and genetic manipulation. This revealed epistatic (here, strain-dependent) effects of key genetic changes affecting horizontal plasmid transfer. Several genetic changes involved mobile elements and pathogenicity islands. Rapid strain-specific evolution can thus outweigh ancestral phenotypes as a predictor of plasmid stability. Accounting for strain-specific plasmid evolution in natural populations could improve our ability to anticipate and manage successful bacterium–plasmid combinations.
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影响因子：
2.8
作者：
Bates, S;Roscoe, RA;Wilkins, BM
通讯作者：
Wilkins, BM
影响因子：
4.5
作者：
Guynet C;Cuevas A;Moncalián G;de la Cruz F
通讯作者：
de la Cruz F
DOI：
10.1038/s41396-018-0276-9
发表时间：
2019-03
期刊：
The ISME journal
影响因子：
--
作者：
Bottery MJ;Wood AJ;Brockhurst MA
通讯作者：
Brockhurst MA
影响因子：
4.5
作者：
Baharoglu Z;Bikard D;Mazel D
通讯作者：
Mazel D
影响因子：
5.8
作者：
Li, Heng
通讯作者：
Li, Heng