Horizontal gene transfer facilitates the spread of antibiotic resistance genes, which constitutes a global challenge. However, the evolutionary trajectory of the mobile colistin resistome in bacteria is largely unknown. To investigate the coevolution and fitness cost of the colistin resistance genes in wild strains, different assays to uncover the genomic dynamics of mcr‐1 and mcr‐3 in bacterial populations are utilized. Escherichia coli strains harboring both mcr‐1 and mcr‐3.1/3.5 are isolated and mcr genes are associated with diverse mobile elements. Under exposure to colistin, the mcr‐1‐bearing resistome is stably inherited during bacterial replication, but mcr‐3 is prone to be eliminated in populations of certain strains. In the absence of colistin, the persistence rates of the mcr‐1 and mcr‐3‐bearing subclones varies depending on the genomic background. The decay of the mcr‐bearing bacterial populations can be mediated by the elimination of mcr‐containing segments, large genomic deletions, and plasmid loss. Mobile elements, including plasmids and transposons, are double‐edged swords in the evolution of the resistome. The findings support the idea that antibiotic overuse accounts for global spread of multidrug‐resistant (MDR) bacteria. Therefore, stringent regulation of antibiotic prescription for humans and animals should be performed systematically to alleviate the threat of MDR bacteria.

中文翻译：

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通过纳米孔测序对大肠杆菌菌株 mcr 基因协同进化进行全面的基因组研究

水平基因转移促进了抗生素抗性基因的传播，这是一个全球性的挑战。然而，细菌中可移动的粘菌素抗性组的进化轨迹在很大程度上是未知的。为了研究野生菌株中粘菌素抗性基因的协同进化和适应性成本，利用不同的测定来揭示细菌群体中mcr-1和mcr-3的基因组动态。分离出同时含有mcr-1和mcr-3.1/3.5的大肠杆菌菌株，并且mcr基因与多种可移动元件相关。在接触粘菌素的情况下，带有mcr-1的耐药基因组在细菌复制过程中稳定遗传，但mcr-3在某些菌株群体中很容易被消除。在没有粘菌素的情况下，带有mcr-1和mcr-3的亚克隆的持续率根据基因组背景而变化。携带mcr的细菌群体的衰退可以通过含有mcr的片段的消除、大量基因组缺失和质粒丢失来介导。移动元件，包括质粒和转座子，是抗性组进化中的双刃剑。研究结果支持抗生素过度使用导致多重耐药（MDR）细菌在全球传播的观点。因此，应系统地对人和动物的抗生素处方进行严格监管，以减轻耐多药细菌的威胁。