Tracing the evolutionary genomics of bla_NDM-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 Tn125 (ΔTn125) unit across all plasmids, suggesting a common genetic vehicle for its dissemination. Further structural analysis indicated the presence of ISCR1 adjacent to ΔTn125, with the entire resistance region bounded by IS26 elements, implying that ISCR1 may facilitate the capture and mobilization of bla_NDM-5, while IS26 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 ΔTn125 unit, and this plasmid type may have formed a regional epidemic in eastern China. ISCR1 likely plays a key role in capturing ΔTn125 and initiating bla_NDM-5 transfer, while IS26 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.