Characterization of the global distribution and diversified plasmid reservoirs of the colistin resistance gene mcr-9

Ying Li,Yan Gao,Zhikun Zhang,Xiaoyi Dai,Luhua Zhang,Jing Zeng

doi:10.1038/s41598-020-65106-w

Abstract

The emergence and spread of mobilized colistin resistance (mcr) genes have triggered extensive concerns worldwide. Here, we characterized the global distribution of mcr-9, a newly-identified variant of mcr, by assembling the data set of mcr-9-positive isolates from GenBank database and the literature available. Genetic features of all the mcr-9-harboring plasmids were determined by bioinformatic analysis. We showed that mcr-9 is globally distributed in 21 countries across six continents, with a wide dissemination among various species of Enterobacteriaceae strains from human, animal, food and environment. IncHI2-ST1 plasmids were found to be the predominant replicon type carrying mcr-9. Comparative genomics highlighted that IncHI2-type plasmids may also serve as a critical reservoir of mcr-9, from which different types of circulating plasmids acquired the mcr-9. Results revealed that the rcnR-rcnA-pcoE-pcoS-IS903-mcr-9-wbuC structure was consistent in most mcr-9 cassettes, suggesting a relatively unitary model involved in the mobilization of mcr-9. It is most likely that the spread of mcr-9 was mainly attributed to the conjugation and recombination events of mcr-9-carrying plasmids. In summary, our results provide a comprehensive picture of the distribution and genetic environment of mcr-9, and demonstrate the central roles played by IncHI2 plasmids in the worldwide dissemination of mcr-9.

Highlights

The emergence and spread of mobilized colistin resistance genes have triggered extensive concerns worldwide
Here we studied the geographic and host distribution of mcr-9-carrying strains, and investigated the genomic features of various types of mcr-9-harboring plasmids from an extensive collection of publicly available sequence data sourced from the NCBI repository by bioinformatics analysis
Our findings suggested that these untyped plasmids were most likely to have acquired the mcr-9 gene from IncHI2-type plasmids by multiple recombination events, and pLEC-b38d might have evolved earlier with the possibility of different patterns for the acquisition and dissemination of mcr-9

Summary

Introduction

The emergence and spread of mobilized colistin resistance (mcr) genes have triggered extensive concerns worldwide. Since the initial discovery of a plasmid-mediated mobilized colistin resistance gene (mcr-1) in China in late 20154, a number of diversified bacterial strains carrying mcr-1 have been detected across over 50 countries covering six continents[5]. Little information is available about the global epidemiology and dissemination patterns of mcr-9 To explore these issues, here we studied the geographic and host distribution of mcr-9-carrying strains, and investigated the genomic features of various types of mcr-9-harboring plasmids from an extensive collection of publicly available sequence data sourced from the NCBI repository by bioinformatics analysis. Our findings may contribute to a better understanding of the prevalence and dissemination of the newly identified mcr-9 gene, and be helpful for developing better strategies to manage its spread

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Results

Conclusion