Bridging the phylodynamic antimicrobial resistance of Salmonella in Southeast Asia and Hong Kong through a One Health Lens.

Drug-resistant Salmonella significantly contributes to the global antimicrobial resistance (AMR) crisis. Understanding its transmission dynamics across human, animal, environmental, and food systems is crucial for effective disease control and strategic planning. This study presents an integrated One Health analysis utilizing whole-genome sequencing of 3076 Salmonella isolates from Southeast Asia and Hong Kong. We assessed genetic relatedness, antibiotic resistance profiles, and phylodynamics across human (n = 915), animal (n = 282), environmental (n = 250), and food sectors (n = 1629). The predominant serovar identified was S. Weltevreden, followed by S. enteritidis, S. typhi, S. typhimurium, and S. Rissen, each exhibiting sequence type (ST)-specific strains. Certain serovars displayed host specificity which being exclusive to particular sectors. Notably, over 50 % of isolates originated from food and animal feed sources. Presence of resistance-associated genes was diverse and leading to multidrug-resistant (MDR) mechanisms evolved over five decades. Specific STs, including S. typhi ST1, S. typhimurium ST34, and S. Rissen ST469, exhibited MDR profiles in certain regions that characterized by ASSuT- and ACSSuT- resistance-associated genes. The inferred migration dynamics of S. Weltevreden indicated significant ancestral lineage movement and cross-border transmission underscoring the flow of AMR genes and pathogens within the One Health framework. Our findings highlight the dynamic transmission of AMR Salmonella across interconnected sectors. This underscores the importance of One Health strategies in mitigating the global escalation of AMR.