Abstract
Background/Objectives: We analyzed the whole-genome sequences of ciprofloxacin-resistant (CIP-R) enteropathogenic Escherichia coli (EPEC) ST752 isolates in South Korea to characterize their molecular epidemiology. This lineage has emerged as the predominant CIP-R EPEC clone in South Korea, accounting for 28.8% of human clinical isolates and circulating within the One Health interface. Methods: We performed whole-genome sequencing (WGS) and reference-based core-genome single-nucleotide polymorphism (SNP) analysis on 26 CIP-R EPEC ST752 isolates (19 human clinical and 7 poultry-derived isolates). To elucidate their evolutionary history and transmission dynamics, Bayesian phylodynamic and phylogeographic reconstructions were implemented by integrating domestic isolates with a global genome dataset (n = 508). Results: Isolates from human and poultry sources clustered together with an identical virulence profile and minimal genetic distance. The Bayesian molecular clock analysis estimated that the time to the most recent common ancestor of the South Korean clade was 2000.65. Moreover, the phylogeographic analysis supported statistical evidence (Bayes factor 32.16) for the introduction of this lineage into South Korea from Denmark and revealed a strongly supported host transition from humans to poultry (Bayes factor > 10,000), although this requires cautious interpretation due to limited temporal sampling of poultry isolates. Conclusions: Continued integrated One Health surveillance across human, animal, and environmental reservoirs is needed to monitor and prevent the spread of high-risk antimicrobial-resistant clones.