Clonal and plasmid-mediated dissemination of mcr-1 in Escherichia coli strains at the human-companion animal interface: Genomic characterisation of colistin resistance plasmids.

The global emergence of plasmid-mediated colistin resistance (mcr-1) gene poses a critical threat to human and animal health due to its ability for horizontal dissemination. While the role of food-producing animals is well recognised, the contribution of companion animals and household environments to the persistence and circulation of mcr-1 remains poorly understood. In this study, we investigated the genetic relatedness of mcr-1-positive Escherichia coli strains and their associated plasmids from dogs and their cohabiting humans in Portugal (2018-2020). Whole-genome sequencing, was performed on 17 strains, including repeated sampling from the same hosts over time. Core genome SNP analysis revealed clonal relatedness among several strains from the same host and between household members (≤6 SNPs). A total of 14 mcr-1-harbouring plasmids were identified and classified into three major incompatibility groups: IncX4 (n = 2), IncHI2 (n = 5), and IncI2 (n = 7). IncX4 plasmids were detected in clonally related strains from the same human host and were identical, indicating maintenance within a persistent lineage. A subset of IncI2 plasmids formed a closely related cluster (1-6 SNPs) across genetically distinct hosts, supporting the possibility of horizontal dissemination. IncHI2 plasmids displayed greater structural diversity and carried multiple antimicrobial and metal resistance determinants. Notably, chromosomal integration of mcr-1 was identified in three strains, suggesting a potential pathway for stabilistion of colistin resistance. Overall, these findings highlight the combined role of clonal expansion and plasmid circulation in shaping the epidemiology of mcr-1 genes in community settings, reinforcing the importance of genomic surveillance within a One Health framework.