Scholarlink

<p>Pathogenic bacteria continually evolve under antimicrobial pressure through acquired resistance genes, making it crucial to understand their evolutionary strategies. We identify a clinical <i>Klebsiella pneumoniae</i> isolate resistant to ceftazidime/avibactam (CZA), harboring heterogeneous multicopy <i>bla</i><sub>CTX-M</sub>, among which a <i>bla</i><sub>CTX-M-249</sub> variant mediates CZA resistance. Both <i>bla</i><sub>CTX-M-249</sub> and its closely related allele <i>bla</i><sub>CTX-M-65</sub> are dominant within the clonal population and are located at two loci on the same plasmid, with their proportions shifting under antibiotic pressure. Using experimental and mathematical models, we demonstrate that the heterogeneous arrangement of <i>bla</i><sub>CTX-M</sub> variants on the same plasmid confers greater stability and competitive advantage than that across separate plasmids, particularly during drug switching. Re-analysis of large genomic datasets supports the universality of this phenomenon. Our findings reveal an evolutionary strategy in which β-lactamase genes, through multicopy heterogeneity on a single plasmid, ensure stable inheritance of resistance and enhance bacterial adaptability under fluctuating clinical antibiotic pressures.</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

Heterogeneous multicopy of blaCTX-M variants on the same plasmid enhances evolutionary adaptability in clinical Klebsiella pneumoniae

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月7日

查看全文
  • Rui Weng,
  • Jingyi Zhu,
  • Xueqing Wu,
  • Qiucheng Shi,
  • Yue Li,
  • Junxin Zhou,
  • Yanfei Wang,
  • Yinping Wang,
  • Weiyi Huang,
  • Haiyang Liu,
  • Sai Qiao,
  • Ying Chen,
  • Jinzheng Ren,
  • Ping Zhang,
  • Jingjing Quan,
  • Dongdong Zhao,
  • Xiaoting Hua,
  • Xiaoxing Du,
  • Jiawei Wang,
  • Yunsong Yu,
  • Yan Jiang

摘要

Pathogenic bacteria continually evolve under antimicrobial pressure through acquired resistance genes, making it crucial to understand their evolutionary strategies. We identify a clinical Klebsiella pneumoniae isolate resistant to ceftazidime/avibactam (CZA), harboring heterogeneous multicopy blaCTX-M, among which a blaCTX-M-249 variant mediates CZA resistance. Both blaCTX-M-249 and its closely related allele blaCTX-M-65 are dominant within the clonal population and are located at two loci on the same plasmid, with their proportions shifting under antibiotic pressure. Using experimental and mathematical models, we demonstrate that the heterogeneous arrangement of blaCTX-M variants on the same plasmid confers greater stability and competitive advantage than that across separate plasmids, particularly during drug switching. Re-analysis of large genomic datasets supports the universality of this phenomenon. Our findings reveal an evolutionary strategy in which β-lactamase genes, through multicopy heterogeneity on a single plasmid, ensure stable inheritance of resistance and enhance bacterial adaptability under fluctuating clinical antibiotic pressures.