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<p>Carbapenem-resistant <i>Klebsiella pneumoniae</i> (CR-KP) poses a serious global public health threat due to its rapid dissemination, yet the role of DNA methylation in its pathogenicity and drug resistance remains unclear. This study characterized the methylome and transcriptome of 10 clinical CR-KP and 5 carbapenem-susceptible <i>K. pneumoniae</i> (CS-KP) isolates to investigate epigenetic mechanisms underlying carbapenem resistance. While no significant difference in overall methylation rates was observed between groups, CR-KP strains exhibited 849 differentially methylated regions (DMRs), including 371 hypermethylated and 478 hypomethylated loci, affecting 408 hypermethylated (Hyper-DMGs) and 326 hypomethylated genes (Hypo-DMGs). Functional enrichment analysis identified five methylation-related genes among these DMRs. Transcriptomic profiling revealed 675 differentially expressed genes (DEGs; 521 upregulated, 154 downregulated) in CR-KP. Integrated analysis identified 86 overlapping genes between DMGs and DEGs, which were enriched in 94 GO functions and two KEGG pathways. This study provides the first comprehensive methylome-transcriptome map of CR-KP, uncovering potential epigenetic drivers of carbapenem resistance.</p>

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Genome-Wide DNA Methylation and RNA Analysis Reveal Epigenetic and Transcriptomic Changes in Carbapenem-Resistant Klebsiella pneumoniae Strains

  • 期刊论文

  • 发表日期：

    2025年12月20日

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  • Jia Tao,
  • Liru Wang,
  • Lixin Yan,
  • Xinxin Hu,
  • Wei Hong,
  • Jiale Li,
  • Wei Jia,
  • Jianning Jin

摘要

Carbapenem-resistant Klebsiella pneumoniae (CR-KP) poses a serious global public health threat due to its rapid dissemination, yet the role of DNA methylation in its pathogenicity and drug resistance remains unclear. This study characterized the methylome and transcriptome of 10 clinical CR-KP and 5 carbapenem-susceptible K. pneumoniae (CS-KP) isolates to investigate epigenetic mechanisms underlying carbapenem resistance. While no significant difference in overall methylation rates was observed between groups, CR-KP strains exhibited 849 differentially methylated regions (DMRs), including 371 hypermethylated and 478 hypomethylated loci, affecting 408 hypermethylated (Hyper-DMGs) and 326 hypomethylated genes (Hypo-DMGs). Functional enrichment analysis identified five methylation-related genes among these DMRs. Transcriptomic profiling revealed 675 differentially expressed genes (DEGs; 521 upregulated, 154 downregulated) in CR-KP. Integrated analysis identified 86 overlapping genes between DMGs and DEGs, which were enriched in 94 GO functions and two KEGG pathways. This study provides the first comprehensive methylome-transcriptome map of CR-KP, uncovering potential epigenetic drivers of carbapenem resistance.