Scholarlink

<p><i>Proteus mirabilis</i> has emerged as a clinically significant multidrug-resistant (MDR) pathogen, yet the genomic drivers and dissemination mechanisms of its antimicrobial resistance (AMR) remain poorly characterized. To address this gap, we conducted a pangenome analysis of 2,013 <i>P. mirabilis</i> genomes, including 1,990 publicly available strains and 23 newly sequenced clinical isolates, to delineate the species-wide AMR landscape. Our study identified 197 AMR gene subtypes spanning 12 antibiotic classes, with seven resistance determinants embedded in the core genome. Clinically critical resistance phenotypes—notably to third-generation cephalosporins and carbapenems—were strongly associated with the proliferation of β-lactamase genes (<i>bla</i><sub><i>TEM-1</i></sub>, <i>bla</i><sub><i>CTX-M-15</i>,</sub> <i>bla</i><sub><i>NDM-1</i></sub>) across lineages. Strikingly, 36.4% of AMR genes resided on mobile genetic elements, with conjugative IncC plasmids acting as primary vectors for high-risk resistance cassettes, including β-lactamase (<i>bla</i><sub><i>TEM-1</i></sub>, <i>bla</i><sub><i>NDM-1</i></sub>) and aminoglycoside-modifying [<i>aac(6’)-Ib-cr</i>, <i>aph(3’’)-Ib</i>] genes. Phylogenetic reconstruction revealed that <i>bla</i><sub><i>NDM-1</i></sub>-carrying IncC plasmids formed interspecies clusters with homologs from <i>Klebsiella pneumoniae</i>, <i>Escherichia coli</i>, and <i>Salmonella enterica</i>, demonstrating active cross-genera transmission within <i>Enterobacteriaceae</i>. These findings highlight two parallel evolutionary strategies in <i>P. mirabilis</i>: the conservation of core genome resistance mechanisms and horizontal acquisition of plasmid-borne MDR traits, which provide comprehensive understanding of AMR transmission in the bacterium.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Genomic epidemiology of antimicrobial resistance in Proteus mirabilis: core genome and plasmid-mediated drivers

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月20日

查看全文
  • Peng Zhang,
  • Zhikang Cheng,
  • Yang Cao,
  • Shuangqing Liu,
  • Meiqi Zhao

摘要

Proteus mirabilis has emerged as a clinically significant multidrug-resistant (MDR) pathogen, yet the genomic drivers and dissemination mechanisms of its antimicrobial resistance (AMR) remain poorly characterized. To address this gap, we conducted a pangenome analysis of 2,013 P. mirabilis genomes, including 1,990 publicly available strains and 23 newly sequenced clinical isolates, to delineate the species-wide AMR landscape. Our study identified 197 AMR gene subtypes spanning 12 antibiotic classes, with seven resistance determinants embedded in the core genome. Clinically critical resistance phenotypes—notably to third-generation cephalosporins and carbapenems—were strongly associated with the proliferation of β-lactamase genes (blaTEM-1, blaCTX-M-15, blaNDM-1) across lineages. Strikingly, 36.4% of AMR genes resided on mobile genetic elements, with conjugative IncC plasmids acting as primary vectors for high-risk resistance cassettes, including β-lactamase (blaTEM-1, blaNDM-1) and aminoglycoside-modifying [aac(6’)-Ib-cr, aph(3’’)-Ib] genes. Phylogenetic reconstruction revealed that blaNDM-1-carrying IncC plasmids formed interspecies clusters with homologs from Klebsiella pneumoniae, Escherichia coli, and Salmonella enterica, demonstrating active cross-genera transmission within Enterobacteriaceae. These findings highlight two parallel evolutionary strategies in P. mirabilis: the conservation of core genome resistance mechanisms and horizontal acquisition of plasmid-borne MDR traits, which provide comprehensive understanding of AMR transmission in the bacterium.