Genomic patterns and characterizations of chromosomally-encoded mcr - 1 in Escherichia coli populations

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Genomic patterns and characterizations of chromosomally‑encoded mcr‑1 in Escherichia coli populations Cong Shen1,2, Lan‑Lan Zhong1,2, Furong Ma3, Mohamed Abd El‑Gawad El‑Sayed Ahmed1,2,4, Yohei Doi5,6, Guili Zhang1,2, Yang Liu1,2, Songyin Huang7, Hong‑Yu Li7, Liyan Zhang8, Kang Liao9, Yong Xia3, Min Dai10, Bin Yan11 and Guo‑Bao Tian1,2,12* 

Abstract  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 poten‑ tial 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. Keywords:  mcr-1, Colistin, Antimicrobial resistance, Genomic pattern, Chromosome, Insertion sequence, Phage Short report The emergence and rapid dissemination of plasmidmediated mobile colistin resistance gene (mcr-1) have become a severe threat to public health [1]. The predominant carriers of mcr-1 were IncX4, IncI2, and IncHI2 plasmids, which are transferable and adaptive *Correspondence: [email protected] 1 Department of Microbiology, Zhongshan School of Medicine, Sun Yatsen University, 74 Zhongshan 2nd Road, Guangzhou 510080, China Full list of author information is available at the end of the article

plasmid types with broad host range and contributed to the spread of mcr-1 among various sources and bacterial species [2–4]. Besides, recombination of transposons, especially Tn6330 (ISApl1-mcr-1-pap2-ISApl1), the primary vehicle for transmission of mcr-1, and