Abstract
Salmonella Typhimurium and its monophasic variants are major contributors to foodborne illnesses globally, with zoonotic transmission posing significant public health risks. In southern China, persistent salmonellosis cases linked to poultry and pork highlight the need for advanced genomic tools to trace contamination sources and understand transmission dynamics. This study integrates whole-genome sequencing (WGS) and spatiotemporal data to investigate the molecular epidemiology of Salmonella in Jiangxi Province, a region with high incidence of foodborne salmonellosis. Analysis of 206 Salmonella isolates (2015-2021) revealed dominant sequence types (ST34, ST19, ST155, and ST469) associated with human clinical cases and food sources. High-resolution single nucleotide polymorphism (SNP) phylogenetic analysis revealed well-supported, monophasic clades corresponding to the major sequence types. This analysis provided strong genomic evidence for zoonotic transmission, with human clinical isolates being genetically almost identical (≤5 SNPs) to isolates from poultry (ST34/ST19) and pork (ST155/ST469) sources. Clonal clusters of monophasic Typhimurium variants (77.9 % of ST34 isolates) exhibited widespread geographic distribution across 11 prefectures, and the high genetic similarity among isolates suggests potential cross-regional transmission through contaminated food supply chains. High antimicrobial resistance (AMR) rates were detected against ampicillin (68.0 %), tetracycline (61.0 %), and sulfamethoxazole-trimethoprim (54.0 %), with multidrug-resistant (MDR) strains (60.2 %) prevalent in clinical and food-derived isolates. ST34 exhibited the highest MDR prevalence (75.4 %), driven by the presence of Salmonella Genomic Island 1 (SGI1) in many isolates. The β-lactamase gene blaTEM-1 was most prevalent (60.7 %), followed by tet(A) (54.4 %), and sul2 (47.6 %). Point mutations in the quinolone resistance-determining region (QRDR), specifically in gyrA, were identified as the primary mechanism for ciprofloxacin resistance. Spatial clustering identified significant clusters in live poultry markets, slaughterhouses, and retail meat, emphasizing the role of foodborne zoonotic reservoirs. Findings advocate for strengthened One Health interventions, including enhanced AMR monitoring, targeted food safety regulations, and real-time WGS-based surveillance to mitigate zoonotic transmission risks in southern China.