Global Variation in Escherichia coli mcr-1 Genes and Plasmids from Animal and Human Genomes Following Colistin Usage Restrictions in Livestock

Antimicrobial resistance (AMR) is a significant global health threat, with multidrug-resistant (MDR) bacterial clones becoming a major concern. Polymyxins, especially colistin, have reemerged as last-resort treatments for MDR Gram-negative infections. However, colistin use in livestock has spread mobile colistin resistance (<i>mcr</i>) genes, notably <i>mcr-1</i>, impacting human health. In consequence, its livestock use was banned in 2017, originating a natural experiment to study bacterial adaptation. The aim of this work was to analyse the changes in the <i>mcr-1</i> genetic background after colistin restriction across the world. This study analyses 3163 <i>Escherichia coli</i> genomes with the <i>mcr-1</i> gene from human and livestock hosts, mainly from Asia (<i>n</i> = 2621) and Europe (n = 359). Genetic characterisation identifies IncI2 (40.4%), IncX4 (26.7%), and multidrug-resistant IncHI2 (18.8%) as the most common plasmids carrying <i>mcr-1.</i> There were differences in plasmids between continents, with IncX4 (56.6%) being the most common in Europe, while IncI2 (44.8%) was predominant in Asia. Promoter variants related to reduced fitness costs and IS<i>Apl1</i> showed a distinct pattern of association that appears to be associated with adaptation to colistin restriction, which differed between continents. Thus, after the colistin ban, Europe saw a shift to specialised <i>mcr-1</i> plasmids as IncX4, while IS<i>Apl1</i> decreased in Asia due to changes in the prevalence of the distinct promoter variants. These analyses illustrate the evolution of <i>mcr-1</i> adaptation following colistin use restrictions and the need for region-specific strategies against AMR following colistin restrictions.