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<p>Multidrug resistant <i>K. pneumoniae</i> is a public health treat in Pakistan, yet longitudinal genomic data on the evolution of resistance and virulence remain limited. This study integrates phenotypic and whole-genome analyses to explore the evolution of resistance and virulence in clinical isolates. In this study, 39 clinical <i>K. pneumoniae</i> isolates from a single center in Lahore, Pakistan were characterized. Comparative genomic analysis of six representative isolates was performed against 45 historical Pakistani isolates (2010 vs. 2019). Pan-genome analysis, resistance and virulence gene profiling, plasmid replicon identification, genotype-phenotype concordance, and phylogenetic reconstruction was performed. Alarmingly, 90% of isolates were MDR while 13% were extensively drug-resistant. Carbapenem resistance exceeded 60%, mainly due to <i>bla</i><sub><i>NDM−1</i></sub> and <i>bla</i><sub><i>NDM−5</i></sub> in high-risk sequence types ST-15, ST-397 and ST-870. Genotype-phenotype concordance analyses demonstrated strong predictive accuracy for beta-lactams but also revealed discordances against other classes indicative of complex resistance mechanisms. Pan-genome analysis of 51 isolates revealed high levels of genome plasticity, with just 18.7% of genes forming the core genome, and significant increases of accessory genome with a preponderance of virulence-linked factors. Representative isolates produced variable biofilm, with strong producers carrying both adhesion genes and plasmid-borne resistance. Collectively, these findings underscore evolving MDR <i>K. pneumoniae</i> population from Pakistan.</p>

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Longitudinal genomic insights into resistance and virulence dynamics of Klebsiella pneumoniae clinical isolates from Pakistan

  • 期刊论文

  • 发表日期：

    2026年3月23日

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  • Wazeer Muhammed Abdullah,
  • Iqbal Ahmad Alvi,
  • Saba Sana,
  • Shafiq-ur-Rehman,
  • Muhammad Asif

摘要

Multidrug resistant K. pneumoniae is a public health treat in Pakistan, yet longitudinal genomic data on the evolution of resistance and virulence remain limited. This study integrates phenotypic and whole-genome analyses to explore the evolution of resistance and virulence in clinical isolates. In this study, 39 clinical K. pneumoniae isolates from a single center in Lahore, Pakistan were characterized. Comparative genomic analysis of six representative isolates was performed against 45 historical Pakistani isolates (2010 vs. 2019). Pan-genome analysis, resistance and virulence gene profiling, plasmid replicon identification, genotype-phenotype concordance, and phylogenetic reconstruction was performed. Alarmingly, 90% of isolates were MDR while 13% were extensively drug-resistant. Carbapenem resistance exceeded 60%, mainly due to blaNDM−1 and blaNDM−5 in high-risk sequence types ST-15, ST-397 and ST-870. Genotype-phenotype concordance analyses demonstrated strong predictive accuracy for beta-lactams but also revealed discordances against other classes indicative of complex resistance mechanisms. Pan-genome analysis of 51 isolates revealed high levels of genome plasticity, with just 18.7% of genes forming the core genome, and significant increases of accessory genome with a preponderance of virulence-linked factors. Representative isolates produced variable biofilm, with strong producers carrying both adhesion genes and plasmid-borne resistance. Collectively, these findings underscore evolving MDR K. pneumoniae population from Pakistan.