The emergence and transmission of the mobile colistin resistance gene (mcr-1) threatened the extensive use of polymyxin antimicrobials. Accumulated evidence showed that the banning of colistin additive in livestock feed efficiently reduce mcr-1 prevalence, not only in animals but also in humans and environments. However, our previous study has revealed that a small proportion of Escherichia coli could continually carry chromosomally-encoded mcr-1. The chromosomally-encoded events, indicated the existence of stabilized heritage of mcr-1 and revealed a potential threat in the antimicrobial stewardship interventions, are yet to be investigated. In this study, we systematically investigated the genetic basis of chromosomally-encoded mcr-1 in prevalence and potential mechanisms of lineage, plasmid, insertion sequence, and phage. Our results demonstrated that the emergence of chromosomally-encoded mcr-1 could originate from multiple mechanisms, but mainly derived through the recombination of ISApl1/Tn6330. We reported a specific transmission mechanism, which is a phage-like region without lysogenic components, could associate with the emergence and stabilization of chromosomally-encoded mcr-1. These results highlighted the potential origin and risks of chromosomally-encoded mcr-1, which could be a heritable repository and thrive again when confronted with new selective pressures. To the best of our knowledge, this is the first study to systematically reveal the genomic basis of chromosomally-encoded mcr-1, and report a specific transmission pattern involved in phage-like region. Overall, we demonstrate the origin mechanisms and risks of chromosomally-encoded mcr-1. It highlights the need of public attention on chromosome-encoded mcr-1 to prevent from its reemergence.

中文翻译：

---

基因组的模式和染色体编码的表征MCR - 1在大肠杆菌群体

流动大肠粘菌素抗性基因（mcr-1）的出现和传播威胁着多粘菌素抗微生物剂的广泛使用。累积的证据表明，禁止在牲畜饲料中添加粘菌素添加剂有效降低了mcr-1的流行率，不仅在动物中而且在人类和环境中都如此。但是，我们先前的研究表明，一小部分大肠杆菌可以连续携带染色体编码的mcr-1。染色体编码事件表明存在mcr-1稳定的遗传，并揭示了抗菌管理干预措施中的潜在威胁，尚待研究。在这项研究中，我们系统地研究了染色体编码的mcr-1在谱系，质粒，插入序列和噬菌体的普遍性和潜在机制中的遗传基础。我们的研究结果表明，染色体编码的mcr-1的出现可能源于多种机制，但主要是通过ISApl1 / Tn6330的重组产生的。我们报告了一种特定的传播机制，这是一个没有溶原成分的噬菌体样区域，可能与染色体编码的mcr-1的出现和稳定有关。这些结果突出了染色体编码的mcr-1的潜在来源和风险，该基因可能是可遗传的储存库，并且在面临新的选择压力时会再次兴旺发展。据我们所知，这是第一个系统地揭示染色体编码的mcr-1的基因组基础，并报告涉及噬菌体样区域的特定传播方式的研究。总体而言，我们证明了染色体编码的mcr-1的起源机制和风险。