Global phylogeography and genomic characterization of bla _NDM-1 -positive clinical Proteus mirabilis isolates from China

Carbapenem-resistant Proteus mirabilis (CRPM), largely driven by dissemination of bla _NDM-1 , poses a growing global threat, yet its phylogeographic and genetic patterns remain understudied. We analyzed 16 bla _NDM-1 -harboring CRPM clinical isolates from a tertiary hospital in China (2017–2024) using antimicrobial susceptibility testing, conjugation assays, whole-genome sequencing, and growth experiments. We found that bla _NDM-1 dissemination occurred primarily via plasmids and Salmonella Genomic Island 1 (SGI1), including a novel SGI1-PM16 variant. Early transmission events were associated with Tn 125 -derived elements (ΔTn 125 ), while IS CR1 appeared to mediate rolling-circle transposition and likely facilitated local amplification of resistance cassettes. Additionally, we performed a global genomic epidemiological study of 420 bla _NDM -positive CRPM genomes curated from NCBI (accessed 21 April 2025). ST135 emerged as the predominant clone among CRPM in China. Phylogeographic analysis of P. mirabilis worldwide clarified the geographic prevalence of NDM variants. In the United States, bla _NDM-7 predominates, whereas bla _NDM-1 is most frequent in China. In summary, this study provides crucial insights into the resistance mechanisms and transmission dynamics of CRPM, as well as underscores the need to enhance genomic surveillance and optimize infection control strategies to mitigate the spread of bla _NDM-1 -harboring CRPMs.

IMPORTANCE

To date, the phylogeographic distribution of bla _NDM -carrying CRPMs has not been determined. Our study identified ST135 as the predominant bla _NDM -producing clone, with a distinct global distribution pattern of NDM variants. Furthermore, we elucidated critical bla _NDM-1 transmission mechanisms, revealing both plasmid- and SGI1-mediated dissemination and IS CR1 -driven gene amplification, while also characterizing a novel SGI1-PM16 variant. These findings provide significant new insights into the molecular mechanisms underlying acquired antimicrobial resistance.