Role of mobile genetic elements in the global dissemination of the carbapenem resistance gene bla(NDM).
Role of mobile genetic elements in the global dissemination of the carbapenem resistance gene bla(NDM).
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DOI：
10.1038/s41467-022-28819-2
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发表时间：
2022-03-03
影响因子：
16.6
通讯作者：
Balloux F
中科院分区：
文献类型：
--
作者：
Acman M;Wang R;van Dorp L;Shaw LP;Wang Q;Luhmann N;Yin Y;Sun S;Chen H;Wang H;Balloux F
移动的耐药基因blaNDM编码NDM酶，该酶水解碳青霉烯类，碳青霉烯类是一类用于治疗一些最严重的细菌感染的抗生素。blaNDM基因在多个质粒上分布于各种革兰氏阴性细菌中，通常位于高度重组和富含转座子的基因组区域内，这导致blaNDM全球传播的动力学仍然难以解决。在这里，我们编译了一个包含6000多个含有blaNDM基因的细菌基因组的数据集，其中包括来自中国各地临床和畜牧相关分离株的104个新生成的PacBio杂交组装体。我们开发了一种计算方法来跟踪blaNDM周围的结构变异，这使我们能够识别流行的基因组背景，移动的遗传因素，以及基因全球传播中可能发生的事件。我们估计blaNDM在1985年之前出现在Tn125转座子上，但在2005年首次记录观察后大约十年才达到全球流行。Tn125转座子似乎在blaNDM的早期质粒介导的跳跃中发挥了重要作用，但近年来被包括IS26侧翼假复合转座子和Tn3000在内的其他元件所取代。我们发现携带blaNDM的质粒骨架和分离株的采样位置之间存在很强的关联。这一观察结果表明，blaNDM基因的全球传播主要是由连续的质粒间转座子跳跃驱动的，随后的质粒交换受到更大的限制，这可能是由于质粒适应其特定的细菌宿主。基因blaNDM赋予对碳青霉烯类抗生素的耐药性，其在多个质粒上遍布革兰氏阴性菌。在这里，Acman等人研究了blaNDM在6000多个细菌基因组中传播的动力学基础，并确定了可能参与基因全球传播的移动的遗传元件和特定动员事件。
The mobile resistance gene blaNDM encodes the NDM enzyme which hydrolyses carbapenems, a class of antibiotics used to treat some of the most severe bacterial infections. The blaNDM gene is globally distributed across a variety of Gram-negative bacteria on multiple plasmids, typically located within highly recombining and transposon-rich genomic regions, which leads to the dynamics underlying the global dissemination of blaNDM to remain poorly resolved. Here, we compile a dataset of over 6000 bacterial genomes harbouring the blaNDM gene, including 104 newly generated PacBio hybrid assemblies from clinical and livestock-associated isolates across China. We develop a computational approach to track structural variants surrounding blaNDM, which allows us to identify prevalent genomic contexts, mobile genetic elements, and likely events in the gene’s global spread. We estimate that blaNDM emerged on a Tn125 transposon before 1985, but only reached global prevalence around a decade after its first recorded observation in 2005. The Tn125 transposon seems to have played an important role in early plasmid-mediated jumps of blaNDM, but was overtaken in recent years by other elements including IS26-flanked pseudo-composite transposons and Tn3000. We found a strong association between blaNDM-carrying plasmid backbones and the sampling location of isolates. This observation suggests that the global dissemination of the blaNDM gene was primarily driven by successive between-plasmid transposon jumps, with far more restricted subsequent plasmid exchange, possibly due to adaptation of plasmids to their specific bacterial hosts. Gene blaNDM, conferring resistance to carbapenem antibiotics, is globally distributed across Gram-negative bacteria on multiple plasmids. Here, Acman et al. study the dynamics underlying blaNDM dissemination across over 6000 bacterial genomes, and identify mobile genetic elements and specific mobilisation events likely involved in the gene’s global spread.
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