The global distribution and spread of the mobilized colistin resistance gene mcr-1

Ruobing Wang,Longyang Jin,Liam P Shaw,Zamin Iqbal,Hui Wang,Xavier Didelot,Phelim Bradley,Thamarai Dorai-Schneiders,Xiaojuan Wang,Qing Zhang,Lucy Anne Weinert,Francois Balloux,Qi Wang,Lucy Van Dorp,Adrien Rieux,Yuqing Liu

doi:10.1038/s41467-018-03205-z

Abstract

Colistin represents one of the few available drugs for treating infections caused by carbapenem-resistant Enterobacteriaceae. As such, the recent plasmid-mediated spread of the colistin resistance gene mcr-1 poses a significant public health threat, requiring global monitoring and surveillance. Here, we characterize the global distribution of mcr-1 using a data set of 457 mcr-1-positive sequenced isolates. We find mcr-1 in various plasmid types but identify an immediate background common to all mcr-1 sequences. Our analyses establish that all mcr-1 elements in circulation descend from the same initial mobilization of mcr-1 by an ISApl1 transposon in the mid 2000s (2002–2008; 95% highest posterior density), followed by a marked demographic expansion, which led to its current global distribution. Our results provide the first systematic phylogenetic analysis of the origin and spread of mcr-1, and emphasize the importance of understanding the movement of antibiotic resistance genes across multiple levels of genomic organization.

Highlights

Colistin represents one of the few available drugs for treating infections caused by carbapenem-resistant Enterobacteriaceae
Colistin was largely abandoned as a treatment for bacterial infections in the 1970s owing to its toxicity and low renal clearance, but has been reintroduced in recent years as an antibiotic of ‘last resort’ against multi-drug-resistant infections[1]
The mobilized colistin gene mcr-1 was first described in a plasmid carried by an Escherichia coli isolated in China in April 20112

Summary

Introduction

Colistin represents one of the few available drugs for treating infections caused by carbapenem-resistant Enterobacteriaceae. The recent plasmid-mediated spread of the colistin resistance gene mcr-1 poses a significant public health threat, requiring global monitoring and surveillance. Intensive screening efforts for mcr-1 have found it to be highly prevalent in a number of environmental settings, including the Haihe River in China[18], recreational water at public urban beaches in Brazil[19], and fecal samples from otherwise healthy individuals[20,21]. Both Brazil and China have banned the use of colistin in agriculture, the evidence that mcr-1 can spread within hospital environments even in the absence of colistin use[22] as well as in the community[21] raises the possibility that the spread of mcr-1 will not be contained by these bans. We aim to shed light on these fundamental issues using whole-genome sequencing (WGS) data from 110 novel mcr-1-positive isolates from China in conjunction with an extensive collection of publicly available sequence data sourced from the NCBI repository as well as the Short Read Archive (SRA)

Objectives

Methods

Results

Conclusion