Tracing the evolutionary genomics of blaNDM-harboring Salmonella typhimurium in China

Carbapenem-resistant Salmonella Typhimurium ( S. Typhimurium) is occasionally reported, primarily driven by the dissemination of the bla NDM gene. Although this poses an emerging threat, its phylogenetic structure and epidemiological patterns remain insufficiently studied. We characterized a clinical carbapenem-resistant S. Typhimurium isolate harboring bla NDM−5 from a tertiary hospital in China using antimicrobial susceptibility testing, plasmid conjugation, and stability assays. Whole-genome sequencing was integrated with data from GenBank to perform a series of bioinformatic analyses. The bla NDM−5 gene was located on a conjugative IncFII-type plasmid that demonstrated long-term stability in the recipient strain. Screening of GenBank identified four structurally related bla NDM−5 -carrying plasmids, all from bacterial hosts isolated in eastern Chinese cities. Comparative analysis revealed that bla NDM−5 was embedded within an identical truncated Tn 125 (ΔTn 125 ) unit across all plasmids, suggesting a common genetic vehicle for its dissemination. Further structural analysis indicated the presence of IS CR1 adjacent to ΔTn 125 , with the entire resistance region bounded by IS 26 elements, implying that IS CR1 may facilitate the capture and mobilization of bla NDM−5 , while IS 26 could mediate co-transfer of multiple resistance modules. In addition, we systematically analyzed all available bla NDM -positive S. Typhimurium genomes from GenBank ( n = 28). Notably, all strains originated from China, and ST34 was the dominant clone (24/28, 85.7%) among bla NDM -positive S. Typhimurium. Phylogenetic analysis classified the strains into three major clusters (I–III), showing strong concordance with Multi-Locus Sequence Types (MLST). Plasmid replicon screening identified IncHI2 and IncFII as the most prevalent plasmid types. Resistance gene profiling further confirmed bla NDM−5 as the predominant carbapenemase subtype, followed by bla NDM−1 . This study identifies a conjugative and stable IncFII-type plasmid as an important vector for bla NDM−5 transmission in S. Typhimurium. The plasmid carries the carbapenemase gene within a conserved ΔTn 125 unit, and this plasmid type may have formed a regional epidemic in eastern China. IS CR1 likely plays a key role in capturing ΔTn 125 and initiating bla NDM−5 transfer, while IS 26 facilitates co-mobilization of multidrug resistance modules. Epidemiological analysis further indicates that China is the primary region affected by bla NDM -positive S. Typhimurium, with the ST34 clone and IncHI2/IncFII plasmids acting as potential major drivers of its dissemination. These findings provide a critical foundation for clinical and public health efforts to control the spread of carbapenem-resistant S. Typhimurium.