# 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.

## Key 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.