A community-based One Health approach to the pandemic dynamics of Escherichia coli ST131

Large-scale genomic studies have advanced our understanding of the global dissemination of antimicrobial-resistant (AMR) bacteria, yet most have been limited by inconsistent sampling periods, heterogeneous geographic coverage, and weak epidemiological linkages among isolates. Consequently, the fine-scale processes underlying the establishment and maintenance of AMR pandemics remain unclear. To address these limitations, we established a rigorously controlled community- and household-integrated One Health framework that incorporates human, animal, and environmental reservoirs within a single urban area and unified sampling period, focusing on the pandemic fluoroquinolone-resistant (FQ-R) Escherichia coli sequence type (ST) 131. Using this model, we analyzed FQ-R E. coli isolates collected from humans, companion animals, sewage, and livestock in the Sapporo area, Japan, during 2021-2022. Among 2,358 E. coli isolates, 235 FQ-R isolates, including 88 ST131 isolates, underwent genomic analyses based on pan-, accessory-, and core genome data. These analyses revealed high clonal diversity but clear population structuring within ST131, with several subclusters shared between human and companion animal sources. High-resolution core genome SNP analysis delineated community-level transmission dynamics, demonstrating ST131 carriage among healthy humans and suggesting asymptomatic human-to-human spread and household-level human-companion animal transmission. These carriage isolates harbored multiple AMR genes and virulence factors and exhibited high genetic similarity to clinical isolates, indicating potential contributions to hospital-associated infections. Phylogenetic integration with international ST131 genomes demonstrated that transmission events in Sapporo are embedded within the broader global expansion of ST131. This study provides a scalable model for resolving local-to-global AMR dissemination and underscores the need for community- and household-level interventions within a One Health framework.