Genomic Characterization of Colistin and Fluoroquinolone Resistance in Multidrug-Resistant Escherichia coli from Diseased Food-Producing Animals in Taiwan.

Background: The global spread of antimicrobial resistance in Escherichia coli (E. coli) from food-producing animals is a critical concern within the One Health framework, particularly because of the potential transmission of clinically relevant resistance determinants across the animal-environment-human interface. Although extended-spectrum β-lactamase (ESBL)-producing E. coli strains have been widely characterized, the genomic mechanisms underlying resistance to the last-resort and critically important antimicrobials colistin and fluoroquinolones remain incompletely understood in animal-associated populations. This study characterized these resistance mechanisms in multidrug-resistant (MDR) E. coli from diseased food-producing animals. Methods: We used whole-genome sequencing (WGS) to characterize 77 MDR E. coli isolates from diseased livestock and poultry in Taiwan and analyzed the underlying resistance mechanisms and their co-occurrence. Results: Plasmid-mediated colistin resistance genes, including mcr-1.1, mcr-3.1, and mcr-3.5, were identified alongside chromosomal mutations, such as pmrB substitutions, indicating multiple evolutionary pathways to colistin resistance. Fluoroquinolone resistance was driven by both chromosomal mutations in quinolone resistance-determining regions and plasmid-mediated quinolone resistance genes, including qnr variants and aac(6')-Ib-cr. Notably, the frequent co-occurrence of resistance determinants targeting multiple antimicrobial classes suggests the presence of mobile genetic elements facilitating horizontal gene transfer. Conclusions: Although a subset of isolates overlapped with those reported in our previous ESBL-focused study, the present work presents a comprehensive genomic dissection of resistance mechanisms beyond β-lactamases. The convergence of colistin, fluoroquinolone, and ESBL-associated resistance determinants within individual isolates highlights the potential role of food-producing animals as reservoirs of multidrug resistance, with potential implications for cross-sectoral transmission. These findings underscore the importance of integrated surveillance strategies addressing potential zoonotic transmission under the One Health framework.