Global Variation in 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 () genes, notably , 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 genetic background after colistin restriction across the world. This study analyses 3163 genomes with the gene from human and livestock hosts, mainly from Asia ( = 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 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 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 plasmids as IncX4, while IS decreased in Asia due to changes in the prevalence of the distinct promoter variants. These analyses illustrate the evolution of adaptation following colistin use restrictions and the need for region-specific strategies against AMR following colistin restrictions.