Genomic epidemiology of Salmonella Typhimurium in Guizhou, China (2019-2023): high prevalence of MDR, plasmid-associated resistance, and shared genomic lineages.

Salmonella Typhimurium (S. Typhimurium) is a leading cause of bacterial gastroenteritis worldwide, and its escalating antimicrobial resistance (AMR) poses a critical threat to global public health. Nevertheless, epidemiological and genomic data for this pathogen in Guizhou Province remain limited. We integrated phenotypic and genomic analyses of 103 clinical S. Typhimurium isolates, collected from nine cities between 2019 and 2023, to characterize their genetic backgrounds, resistance mechanisms, and evolutionary dynamics. The isolates exhibited persistently high resistance to conventional antibiotics. Multidrug resistance (MDR) was universal (100% during 2019-2021), with extensively drug-resistant (XDR) isolates emerged in 2020. Substantial resistance to first-line antibiotics was also observed, including ciprofloxacin (16.5%), ceftazidime (19.4%), cefotaxime (36.9%), and azithromycin (12.6%). Whole-genome sequencing (WGS) identified 61 antimicrobial resistance genes (ARGs) and six distinct point mutations. Efflux pump-associated genes were widely distributed, and ARGs conferring tetracyclines and sulfonamides were detected at high frequencies. Resistance genotypes correlated well with phenotypes for azithromycin, ceftazidime, ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, and tetracycline (Kappa: 0.48-0.74). Twenty plasmid replicons were detected, with IncF (24.3%), IncI1-I (15.5%), and IncHI2 (13.6%) being the most prevalent. Notably, ARGs associated with resistance to critically important antibiotics (such as qnr variants, bla CTX-M and bla CMY-2 , and mphA/mrx) were frequently predicted to locate on plasmid-associated contigs. Plasmid diversity expanded significantly over the five-year period, particularly in economically developed cities. Molecular typing identified ST19 and its subtypes, cgST121877 (30.1%) and cgST59516 (12.6%), as the dominant clones, suggesting pronounced regional clonal expansion. Furthermore, phylogenetic analysis revealed close genetic relatedness between Guizhou clinical isolates and human- and livestock-derived isolates from other Chinese provinces. These findings highlight the cross-regional and cross-species circulation of shared genomic lineages, suggesting complex ecological networks that may involve the food supply chain. Implementing an integrated "One Health" surveillance strategy is critical to track and limit the circulation of these resistant lineages and mitigate the associated public health threat.