Tracking Global Transmission Dynamics of the Plasmid-Mediated mcr Gene: A Genomic Epidemiological Analysis

TL;DR

This study tracks how antibiotic resistance genes called mcr spread globally through plasmids in different bacteria, showing how they move across species and regions over time.

Contribution

The study reveals the spatiotemporal dynamics of mcr-carrying plasmids and identifies key transmission patterns across bacterial genera and geographic regions.

Findings

Cross-genera transmission of mcr-carrying plasmids shifted from IncHI2/HI2A to IncI2 and then to IncX4 over time.

IncX4 plasmids originated in animal hosts around 1990 and spread globally through horizontal gene transfer.

IncP1 plasmids are significant vectors for mcr-1 and mcr-3 in Southeast Asia, highlighting the need for surveillance.

Abstract

The emergence and spread of mobile colistin resistance (mcr) genes pose a significant challenge in controlling multidrug-resistant Gram-negative pathogens. Understanding the epidemiology of mcr-carrying plasmids is essential for mitigating their dissemination across humans, animals, and the environment. To characterize their spatiotemporal dynamics on a global scale, we analyzed an extensive collection of 5,549 mcr-carrying plasmids spanning 1995 to the present. We found that cross-genera transmission patterns of mcr-carrying plasmids varied across four distinct periods. Initially, IncHI2/HI2A plasmids provided a survival advantage across genera and regions, followed by IncI2, and ultimately by IncX4. Moreover, the three plasmid lineages (i.e., IncX4, IncI2, and IncHI2/HI2A) have reached a stable distribution across diverse bacterial hosts and geographic regions through horizontal gene transfer and clonal expansion. By integrating sequence similarity clustering of plasmids and mcr-related genetic environments, we identified 79 cross-genus, 43 intra-E. coli, and 10 intra-S. enterica transmission units. Molecular dating analysis traced the origin of IncX4 plasmids to 1990 in animal hosts, with phylogenetic evidence indicating potential cross-host, -genus, and -region exchange. Notably, IncP1 plasmids emerged as important vectors of mcr-1 and mcr-3 spread, particularly in Southeast Asia, warranting enhanced surveillance. These findings provide critical insights into the global transmission networks of plasmid-mediated mcr genes and underscore the urgent need for coordinated interventions.

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