One Health phylogenomics of antibiotic-resistant Salmonella enterica reveals cross-source relatedness and detection of mcr-3 -carrying ST34 isolates in Hong Kong

Nontyphoidal Salmonella enterica serovars are a major driver of foodborne illnesses in Hong Kong. Beyond well-recognized extended spectrum beta-lactamase (ESBL)- and carbapenemase-producing strains, colistin resistance remains a critical concern for treating severe multidrug-resistant (MDR) infections. While routine surveillance exists, the distribution and genomic epidemiology of antimicrobial resistance (AMR) across interconnected reservoirs remain insufficiently characterized. Applying a One Health framework, this study investigated cross-sectoral genetic relatedness and shared AMR determinants by analyzing local clinical and retail meat Salmonella isolates alongside a reference set of publicly available regional genomes representing human, food, animal, and environmental sectors. We report the detection of mcr-positive S. Typhimurium ST34 lineage human clinical isolates in Hong Kong, including mcr-1.1 and mcr-3.1, not previously detected in our regional dataset or local genomic surveillance archives. Nanopore sequencing revealed that mcr-3 was carried on a mosaic IncC/IncFII plasmid displaying structural features consistent with a recombinant origin involving genetic elements shared between clinical Salmonella and chicken-derived E. coli plasmid backbones. These plasmids demonstrated high in vitro transferability to diverse Enterobacterales, including K. pneumoniae, Citrobacter and Enterobacter spp. Additionally, identification of a transferable blaNDM-5­-carrying plasmid from a pork-derived isolate highlights the presence and in vitro mobility of clinically important carbapenenemase determinants within food-derived strains. Comparative phylogenomic analysis of 1,458 Salmonella genomes identified mixed-source genomic clusters among major sequence types (ST19, ST34, ST155, ST40, ST17, and ST2529), indicating genomic relatedness across multiple One Health sectors. These findings support the utility of integrated One Health genomic surveillance frameworks to monitor multidrug-resistant Salmonella lineages.