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<p>Carbapenem-resistant <i>Pseudomonas aeruginosa</i> (CRPA) represents a major health threat due to its extensive resistance to last‑resort antibiotics. Although carbapenemase determinants are key drivers of global CRPA dissemination, comprehensive genomic investigations delineating their chromosomal versus plasmid contexts are sparse. Therefore, in this study we conducted an integrated comparative genomic analysis of <i>P. aeruginosa</i> strains harboring major carbapenemase genes (<i>bla</i><sub>GES</sub>, <i>bla</i><sub>KPC</sub>, <i>bla</i><sub>SPM</sub>, <i>bla</i><sub>NDM</sub>, <i>bla</i><sub>VIM</sub>, and <i>bla</i><sub>IMP</sub>), with a focus on their genomic localization, surrounding genetic architectures, and associated mobility elements. Chromosomes and plasmids carrying carbapenemase genes (retrieved from GenBank through 2025) were systematically characterized for sequence types, genetic environments, co‑occurring antimicrobial resistance genes (ARGs), and plasmid mobility features using established bioinformatic pipelines. Genetic relatedness of plasmids was inferred via ClustAGE and UPGMA clustering. Multilocus sequence typing (MLST) was employed to assess clonal relatedness of isolates. Among 398 carbapenemase-carrying genomic fragments, <i>bla</i><sub>VIM</sub>, <i>bla</i><sub>KPC</sub>, and <i>bla</i><sub>GES</sub> were the most prevalent. <i>bla</i><sub>VIM</sub>, <i>bla</i><sub>IMP</sub>, and <i>bla</i><sub>NDM</sub> showed broad geographic distribution. High-risk clones including ST235, ST111, ST233, ST357, ST308, and ST277 were among the most common sequence types. Notably, a minority (10.28%) of carbapenemase-carrying plasmids were predicted to be conjugative or mobilizable. The <i>mex</i>, and <i>opr</i> families, and <i>sul1</i> were most frequent co-existing ARGs. These findings highlight the dominant role of established high-risk lineages and integrative mobile elements in shaping the epidemiology of resistance. The relatively low frequency of self-transmissible plasmids suggests that horizontal resistance dissemination is likely mediated through a combination of integrative mobile genetic elements and clonal expansion. Our results underscore the necessity for enhanced genomic surveillance strategies that integrate clonal tracking with mobile resistance determinant monitoring to better understand and control the spread of carbapenem resistance.</p>

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Comparative genome analysis of carbapenemase-producing Pseudomonas aeruginosa: gene diversity, clonal distribution, and genome dynamics

  • 期刊论文

  • 发表日期：

    2026年6月3日

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  • Narjes Noori Goodarzi,
  • Farzad Badmasti

摘要

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) represents a major health threat due to its extensive resistance to last‑resort antibiotics. Although carbapenemase determinants are key drivers of global CRPA dissemination, comprehensive genomic investigations delineating their chromosomal versus plasmid contexts are sparse. Therefore, in this study we conducted an integrated comparative genomic analysis of P. aeruginosa strains harboring major carbapenemase genes (blaGES, blaKPC, blaSPM, blaNDM, blaVIM, and blaIMP), with a focus on their genomic localization, surrounding genetic architectures, and associated mobility elements. Chromosomes and plasmids carrying carbapenemase genes (retrieved from GenBank through 2025) were systematically characterized for sequence types, genetic environments, co‑occurring antimicrobial resistance genes (ARGs), and plasmid mobility features using established bioinformatic pipelines. Genetic relatedness of plasmids was inferred via ClustAGE and UPGMA clustering. Multilocus sequence typing (MLST) was employed to assess clonal relatedness of isolates. Among 398 carbapenemase-carrying genomic fragments, blaVIM, blaKPC, and blaGES were the most prevalent. blaVIM, blaIMP, and blaNDM showed broad geographic distribution. High-risk clones including ST235, ST111, ST233, ST357, ST308, and ST277 were among the most common sequence types. Notably, a minority (10.28%) of carbapenemase-carrying plasmids were predicted to be conjugative or mobilizable. The mex, and opr families, and sul1 were most frequent co-existing ARGs. These findings highlight the dominant role of established high-risk lineages and integrative mobile elements in shaping the epidemiology of resistance. The relatively low frequency of self-transmissible plasmids suggests that horizontal resistance dissemination is likely mediated through a combination of integrative mobile genetic elements and clonal expansion. Our results underscore the necessity for enhanced genomic surveillance strategies that integrate clonal tracking with mobile resistance determinant monitoring to better understand and control the spread of carbapenem resistance.