Global phylogeography and genomic characterization of bla_NDM-1-positive clinical Proteus mirabilis isolates from China.

IF 4.6 2区生物学 Q1 MICROBIOLOGY

mSystems Pub Date : 2025-09-22 DOI:10.1128/msystems.00758-25

Jingyi Guo, Haotian Xu, Chengjin Wu, Hongyan Yu, Lexuan Yang, Yan Qi, Xiuyun Zuo, Hongyin Yang, Linyue Zhang, Yunsong Yu, Xi Li

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引用次数: 0

Abstract

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 Tn125-derived elements (ΔTn125), while ISCR1 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 ISCR1-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.

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中国临床奇异变形杆菌blandm -1阳性分离株的全球系统地理和基因组特征

碳青霉烯抗性奇异变形杆菌（CRPM）主要由blaNDM-1的传播驱动，对全球构成日益严重的威胁，但其系统地理和遗传模式仍未得到充分研究。我们对2017-2024年从中国某三级医院分离的16株携带blandm -1的CRPM临床分离株进行了抗菌药敏试验、偶联试验、全基因组测序和生长实验。我们发现blaNDM-1主要通过质粒和沙门氏菌基因组岛1 （SGI1）传播，包括一种新的SGI1- pm16变体。早期传播事件与tn125衍生元件相关（ΔTn125），而ISCR1似乎介导滚动圈转位，并可能促进抗性磁带的局部扩增。此外，我们对从NCBI中提取的420个blandm阳性CRPM基因组进行了全球基因组流行病学研究（获取于2025年4月21日）。ST135成为中国CRPM的优势无性系。对世界范围内奇异假单胞菌的系统地理学分析阐明了NDM变异的地理流行。在美国，blaNDM-7占主导地位，而blaNDM-1在中国最为常见。总之，本研究为CRPM的耐药机制和传播动力学提供了重要的见解，并强调了加强基因组监测和优化感染控制策略的必要性，以减轻携带blandm -1的CRPM的传播。重要性：迄今为止，携带blandm的crpm的系统地理分布尚未确定。我们的研究确定ST135是主要的blandm产生克隆，具有明显的NDM变异的全球分布模式。此外，我们阐明了blaNDM-1的关键传播机制，揭示了质粒和sgi1介导的传播和iscr1驱动的基因扩增，同时还表征了一种新的SGI1-PM16变体。这些发现为获得性抗菌素耐药性的分子机制提供了重要的新见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

mSystems Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

10.50

自引率

3.10%

发文量

308

审稿时长

13 weeks

期刊介绍： mSystems™ will publish preeminent work that stems from applying technologies for high-throughput analyses to achieve insights into the metabolic and regulatory systems at the scale of both the single cell and microbial communities. The scope of mSystems™ encompasses all important biological and biochemical findings drawn from analyses of large data sets, as well as new computational approaches for deriving these insights. mSystems™ will welcome submissions from researchers who focus on the microbiome, genomics, metagenomics, transcriptomics, metabolomics, proteomics, glycomics, bioinformatics, and computational microbiology. mSystems™ will provide streamlined decisions, while carrying on ASM''s tradition of rigorous peer review.