{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T17:11:05Z","timestamp":1793121065659,"version":"4.5.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      Carbapenem-resistant\n                      <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                      (CRKP) has emerged as a major global health threat due to its resistance to carbapenems. As the mechanisms underlying carbapenem resistance in CRKP remain incompletely understood, we seek to provide important insights into the clinical and genomic characteristics of CRKP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A total of 40 CRKP and 42 carbapenem-susceptible\n                      <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                      (CSKP) isolates were collected from a tertiary hospital in Wuhan, China. Integrating 2,460 publicly available\n                      <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                      genomes, we conducted a comprehensive analysis of clinical risk factors, resistance and virulence gene profiles, plasmid replicon composition, core genome SNP-based phylogeny, pan-genome structure, and genome-wide single-nucleotide variants and insertions\/deletions (SNVs\/InDels) variation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Clinical analysis identified a Charlson comorbidity index &amp;gt; 3 and respiratory tract infections as independent risk factors for CRKP infection. Genomic comparisons revealed that CRKP strains harbored more resistance and virulence genes than CSKP strains, with ST11 being the dominant CRKP clone that frequently carried the\n                      <jats:italic>blaKPC-2<\/jats:italic>\n                      gene. Phylogenetic analysis incorporating public genomes revealed regional differences in sequence type and carbapenemase genotype distributions. Pan-genome analysis demonstrated open pan-genome characteristics in both groups, with cloud genes representing the largest gene category. Comparative genomic analyses revealed distinct SNV and InDel distribution patterns between CRKP and CSKP isolates, while GO annotation of the prioritized variant-associated genes showed broad functional representation across cellular and metabolic processes, transport and responses to stimuli, membrane-associated components, and binding and catalytic functions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      CCI &amp;gt;3 and respiratory tract infection were independently associated with CRKP infection. ST11-\n                      <jats:italic>blaKPC-2<\/jats:italic>\n                      was the predominant epidemic lineage and CRKP isolates carried a greater burden of resistance and virulence determinants than CSKP isolates. Phylogenetic, pan-genomic, and comparative genomic analyses revealed substantial genomic diversity and distinct genomic variation patterns between CRKP and CSKP. These findings provide insights into the clinical risk profile, clonal dynamics, and genomic evolution of CRKP, informing future surveillance and infection control strategies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1881548","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T04:46:28Z","timestamp":1786509988000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrative genomic and clinical analysis of carbapenem-resistant and susceptible Klebsiella pneumoniae isolates from a tertiary hospital in Wuhan"],"prefix":"10.3389","volume":"16","author":[{"given":"Mengling","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences","place":["Wuhan, China"]},{"name":"University of Chinese Academy of Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieyu","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinwen","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences","place":["Wuhan, China"]},{"name":"University of Chinese Academy of Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haizhou","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangbo","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"D690","DOI":"10.1093\/nar\/gkac920","article-title":"CARD 2023: Expanded curation, support for machine learning, and resistome prediction at the Comprehensive Antibiotic Resistance Database","volume":"51","author":"Alcock","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"B2","article-title":"FastQC A Quality Control tool for High Throughput Sequence Data","author":"Andrews","year":"2014"},{"key":"B3","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1089\/cmb.2012.0021","article-title":"SPAdes: A new genome assembly algorithm and its applications to single-cell sequencing","volume":"19","author":"Bankevich","year":"2012","journal-title":"J. Comput. Biology: A. J. Comput. Mol. Cell. Biol."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens12010116","article-title":"Bacterial antibiotic resistance: The most critical pathogens","volume":"12","author":"Biondo","year":"2023","journal-title":"Pathog. (Basel Switzerland)"},{"key":"B5","doi-asserted-by":"publisher","first-page":"5825","DOI":"10.1093\/molbev\/msab293","article-title":"eggNOG-mapper v2: Functional annotation, orthology assignments, and domain prediction at the metagenomic scale","volume":"38","author":"Cantalapiedra","year":"2021","journal-title":"Mol. Biol. Evol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1007\/978-1-4939-9877-7_20","article-title":"PlasmidFinder and in silico pMLST: Identification and typing of plasmid replicons in whole-genome sequencing (WGS)","volume":"2075","author":"Carattoli","year":"2020","journal-title":"Methods Mol. Biol. (Clifton NJ)"},{"key":"B7","doi-asserted-by":"publisher","first-page":"D325","DOI":"10.1093\/nar\/gki008","article-title":"VFDB: A reference database for bacterial virulence factors","volume":"33","author":"Chen","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"fastp: An ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinf. (Oxford England)"},{"key":"B9","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1016\/j.hlife.2024.06.005","article-title":"Understanding carbapenem-resistant hypervirulent Klebsiella pneumoniae: Key virulence factors and evolutionary convergence","volume":"2","author":"Chen","year":"2024","journal-title":"hLife"},{"key":"B10","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.gene.2004.05.008","article-title":"Sequencing and analysis of the large virulence plasmid pLVPK of Klebsiella pneumoniae CG43","volume":"337","author":"Chen","year":"2004","journal-title":"Gene"},{"key":"B11","article-title":"Performance standards for antimicrobial susceptibility testing","volume-title":"CLSI Supplement M100","year":"2020"},{"key":"B12","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1007\/s00431-024-05914-8","article-title":"Burden of viral respiratory infections in the pediatric intensive care unit: Age, virus distribution, and the impact of the COVID-19 pandemic","volume":"184","author":"Cohen","year":"2024","journal-title":"Eur. J. Pediatr."},{"key":"B13","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1007\/978-1-0716-3072-3_19","article-title":"Metagenomics data visualization using R","volume":"2649","author":"Coleman","year":"2023","journal-title":"Methods Mol. Biol. (Clifton NJ)"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1335.e9","DOI":"10.1016\/j.cmi.2023.06.026","article-title":"The problem of Mycobacterium abscessus complex: Multi-drug resistance, bacteriophage susceptibility and potential healthcare transmission","volume":"29","author":"Dedrick","year":"2023","journal-title":"Clin. Microbiol. Infection: Off. Publ. Eur. Soc. Clin. Microbiol. Infect. Dis."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00703-25","article-title":"Lineage-specific evolution and resistance-virulence divergence in Klebsiella pneumoniae ST268: A global population genomic analysis","volume":"69","author":"Dong","year":"2025","journal-title":"Antimicrob. Agents Chemother."},{"key":"B16","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/s1473-3099(17)30489-9","article-title":"A fatal outbreak of ST11 carbapenem-resistant hypervirulent Klebsiella pneumoniae in a Chinese hospital: a molecular epidemiological study","volume":"18","author":"Gu","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/imt2.43","article-title":"Complex heatmap visualization","volume":"1","author":"Gu","year":"2022","journal-title":"iMeta"},{"key":"B18","doi-asserted-by":"publisher","first-page":"2811","DOI":"10.1093\/bioinformatics\/btu393","article-title":"circlize implements and enhances circular visualization in R","volume":"30","author":"Gu","year":"2014","journal-title":"Bioinf. (Oxford England)"},{"key":"B19","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1111\/nyas.12830","article-title":"Mechanisms of drug resistance: Quinolone resistance","volume":"1354","author":"Hooper","year":"2015","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2025.105627","article-title":"Global emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae driven by an IncFII(K34) KPC-2 plasmid","volume":"113","author":"Jiang","year":"2025","journal-title":"EBioMedicine"},{"key":"B21","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat. Methods"},{"key":"B22","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.jgar.2020.09.004","article-title":"Virulence evolution, molecular mechanisms of resistance and prevalence of ST11 carbapenem-resistant Klebsiella pneumoniae in China: A review over the last 10 years","volume":"23","author":"Liao","year":"2020","journal-title":"J. Global Antimicrob. Resist."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofad649","article-title":"The global and regional prevalence of hospital-acquired carbapenem-resistant Klebsiella pneumoniae infection: A systematic review and meta-analysis","volume":"11","author":"Lin","year":"2024","journal-title":"Open Forum Infect. Dis."},{"key":"B24","doi-asserted-by":"publisher","first-page":"7840","DOI":"10.1038\/s41598-021-87332-6","article-title":"The risk of pulmonary tuberculosis after traumatic brain injury","volume":"11","author":"Liu","year":"2021","journal-title":"Sci. Rep."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1099\/mgen.0.001373","article-title":"Genomic and phylogenetic analysis of hypervirulent Klebsiella pneumoniae ST23 in Ireland","volume":"11","author":"Maguire","year":"2025","journal-title":"Microb. Genomics"},{"key":"B26","doi-asserted-by":"publisher","first-page":"CH7","DOI":"10.1128\/9781555819217.ch7","article-title":"Xer site-specific recombination: Promoting vertical and horizontal transmission of genetic information","volume":"2","author":"Midonet","year":"2014","journal-title":"Microbiol. Spectr."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2025.2514092","article-title":"Enterobacterales use capsules, transporters, mobile genetic elements, and other evolutionary adaptations to survive antibiotics exposure in the absence of resistance genes","volume":"16","author":"Mmatli","year":"2025","journal-title":"Virulence"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.cimid.2024.102246","article-title":"Whole genome sequencing of multidrug-resistant Klebsiella pneumoniae from poultry in Noakhali, Bangladesh: Assessing risk of transmission to humans in a pilot study","volume":"114","author":"Munim","year":"2024","journal-title":"Comp. Immunology Microbiol. Infect. Dis."},{"key":"B29","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1093\/molbev\/msu300","article-title":"IQ-TREE: A fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies","volume":"32","author":"Nguyen","year":"2015","journal-title":"Mol. Biol. Evol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"3691","DOI":"10.1093\/bioinformatics\/btv421","article-title":"Roary: Rapid large-scale prokaryote pan genome analysis","volume":"31","author":"Page","year":"2015","journal-title":"Bioinf. (Oxford England)"},{"key":"B31","doi-asserted-by":"publisher","first-page":"D737","DOI":"10.1093\/nar\/gkt1252","article-title":"BacMet: Antibacterial biocide and metal resistance genes database","volume":"42","author":"Pal","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02610-16","article-title":"Importance of clonal complex 258 and IncF(K2-like) plasmids among a global collection of Klebsiella pneumoniae with bla(KPC)","volume":"61","author":"Peirano","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01148-20","article-title":"Emerging antimicrobial-resistant high-risk Klebsiella pneumoniae clones ST307 and ST147","volume":"64","author":"Peirano","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"B34","doi-asserted-by":"publisher","first-page":"2068","DOI":"10.1093\/bioinformatics\/btu153","article-title":"Prokka: Rapid prokaryotic genome annotation","volume":"30","author":"Seemann","year":"2014","journal-title":"Bioinf. (Oxford England)"},{"key":"B35","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1016\/j.ygeno.2019.06.016","article-title":"Prophages contribute to genome plasticity of Klebsiella pneumoniae and may involve the chromosomal integration of ARGs in CG258","volume":"112","author":"Shen","year":"2020","journal-title":"Genomics"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2025.107657","article-title":"Global genomic epidemiology of carbapenemase-producing Klebsiella pneumoniae, 1996\u20132023","volume":"67","author":"Shi","year":"2026","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B37","doi-asserted-by":"publisher","first-page":"2292","DOI":"10.1093\/jac\/dkae227","article-title":"Epidemiology of carbapenem-resistant Klebsiella pneumoniae in China and the evolving trends of predominant clone ST11: a multicentre, genome-based study","volume":"79","author":"Shi","year":"2024","journal-title":"J. Antimicrob. Chemother."},{"key":"B38","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1016\/j.tim.2003.08.006","article-title":"Multi-locus sequence typing: A tool for global epidemiology","volume":"11","author":"Urwin","year":"2003","journal-title":"Trends Microbiol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/s1473-3099(21)00399-6","article-title":"Clinical outcomes and bacterial characteristics of carbapenem-resistant Klebsiella pneumoniae complex among patients from different global regions (CRACKLE-2): a prospective, multicentre, cohort study","volume":"22","author":"Wang","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2024.101083","article-title":"Expansion and transmission dynamics of high risk carbapenem-resistant Klebsiella pneumoniae subclones in China: An epidemiological, spatial, genomic analysis","volume":"74","author":"Wang","year":"2024","journal-title":"Drug Resistance Updates: Rev. Commentaries Antimicrobial Anticancer Chemotherapy"},{"key":"B41","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1038\/s41579-019-0315-1","article-title":"Population genomics of Klebsiella pneumoniae","volume":"18","author":"Wyres","year":"2020","journal-title":"Nat. Rev. Microbiol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"4039","DOI":"10.1093\/molbev\/msab166","article-title":"ggtreeExtra: Compact visualization of richly annotated phylogenetic data","volume":"38","author":"Xu","year":"2021","journal-title":"Mol. Biol. Evol."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1002\/imt2.56","article-title":"Ggtree: A serialized data object for visualization of a phylogenetic tree and annotation data","volume":"1","author":"Xu","year":"2022","journal-title":"iMeta"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.01690-22","article-title":"Clinical and molecular characterizations of carbapenem-resistant Klebsiella pneumoniae causing bloodstream infection in a Chinese hospital","volume":"10","author":"Zhang","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"B45","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1186\/s13756-019-0615-2","article-title":"Clinical, microbiological, and molecular epidemiological characteristics of Klebsiella pneumoniae-induced pyogenic liver abscess in southeastern China","volume":"8","author":"Zhang","year":"2019","journal-title":"Antimicrobial Resistance Infection Control"}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1881548\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T04:46:36Z","timestamp":1786509996000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1881548\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,12]]},"references-count":45,"alternative-id":["10.3389\/fcimb.2026.1881548"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2026.1881548","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,12]]},"article-number":"1881548"}}