{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:56:16Z","timestamp":1792788976924,"version":"4.5.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Health Research","id":[{"id":"https:\/\/ror.org\/00z72fs19","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                      is a major cause of healthcare-associated infections and an important contributor to the global burden of antimicrobial resistance. However, comprehensive genomic epidemiological data on multidrug-resistant (MDR)\n                      <jats:italic>K. pneumoniae<\/jats:italic>\n                      from North India remain limited.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Ninety-six non-duplicate clinical\n                      <jats:italic>K. pneumoniae<\/jats:italic>\n                      isolates collected from a tertiary-care hospital in North India during 2022\u20132024 underwent antimicrobial susceptibility testing and\n                      <jats:italic>de novo<\/jats:italic>\n                      whole-genome sequencing (WGS). Following genomic quality assessment and targeted re-evaluation, 90 genomes were retained for genome-based analyses. MLST and pangenome analyses included 72 and 69 genomes, respectively, according to their respective inclusion criteria. Genome-based analyses included capsular typing, resistome and virulome profiling, plasmid replicon prediction, pangenome analysis, identification of resistance-associated chromosomal mutations, and phylogenomic reconstruction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Phenotypic analysis showed carbapenem resistance in 93\/96 (96.9%) isolates. Genomic analysis identified 32 sequence types, with ST515 (37.5%; 27\/72) as the predominant lineage, while KL62 (60.0%; 54\/90) was the most common capsular locus. The predominant carbapenemase gene was\n                      <jats:italic>bla<\/jats:italic>\n                      <jats:sub>OXA-232<\/jats:sub>\n                      (75.6%; 68\/90), followed by\n                      <jats:italic>bla<\/jats:italic>\n                      <jats:sub>NDM-1<\/jats:sub>\n                      (14.4%; 13\/90) and\n                      <jats:italic>bla<\/jats:italic>\n                      <jats:sub>NDM-5<\/jats:sub>\n                      (8.9%; 8\/90). A total of 82 antimicrobial resistance genes spanning 16 antibiotic classes were identified, with\n                      <jats:italic>fosA<\/jats:italic>\n                      (86\/90, 95.6%),\n                      <jats:italic>oqxA<\/jats:italic>\n                      (85\/90, 94.4%),\n                      <jats:italic>qnrS1<\/jats:italic>\n                      (75\/90, 83.3%), and\n                      <jats:italic>bla<\/jats:italic>\n                      <jats:sub>CTX-M-15<\/jats:sub>\n                      (69\/90, 76.7%) being the most prevalent. Pangenome analysis of 69 genomes identified 13,720 gene families, indicating extensive accessory genome diversity. Resistance-associated mutations involving\n                      <jats:italic>ompK35<\/jats:italic>\n                      ,\n                      <jats:italic>ompK36<\/jats:italic>\n                      ,\n                      <jats:italic>gyrA<\/jats:italic>\n                      ,\n                      <jats:italic>parC<\/jats:italic>\n                      ,\n                      <jats:italic>ramR<\/jats:italic>\n                      , and\n                      <jats:italic>cirA<\/jats:italic>\n                      were identified. Virulence profiling revealed conserved genes for adherence, biofilm formation, secretion systems, and iron acquisition, whereas\n                      <jats:italic>rmpA<\/jats:italic>\n                      and\n                      <jats:italic>rmpA2<\/jats:italic>\n                      were absent. Phylogenomic analysis demonstrated clustering according to sequence type and capsular locus.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study provides a comprehensive genomic characterization of MDR\n                      <jats:italic>K. pneumoniae<\/jats:italic>\n                      circulating in a North Indian tertiary care hospital. The predominance of the ST515 and KL62 lineage, together with high prevalence of\n                      <jats:italic>bla<\/jats:italic>\n                      <jats:sub>OXA-232<\/jats:sub>\n                      , with an extensive accessory genome and diverse resistance determinants, highlights the value of WGS for genomic surveillance of carbapenem-resistant\n                      <jats:italic>K. pneumoniae<\/jats:italic>\n                      and for informing infection prevention and antimicrobial stewardship.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1831365","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:44:17Z","timestamp":1790228657000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive genomic characterization of multidrug-resistant Klebsiella pneumoniae from North India"],"prefix":"10.3389","volume":"17","author":[{"given":"Nargis Kaur","family":"Bali","sequence":"first","affiliation":[{"name":"Sher-i-Kashmir Institute of Medical Sciences","place":["Srinagar, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aktarul Islam","family":"Siddique","sequence":"additional","affiliation":[{"name":"Regional Medical Research Centre (ICMR)","place":["Dibrugarh, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umaya","family":"Majid","sequence":"additional","affiliation":[{"name":"Sher-i-Kashmir Institute of Medical Sciences","place":["Srinagar, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dona","family":"Mathew","sequence":"additional","affiliation":[{"name":"Sher-i-Kashmir Institute of Medical Sciences","place":["Srinagar, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susheem","family":"Ramakrishnan","sequence":"additional","affiliation":[{"name":"Sher-i-Kashmir Institute of Medical Sciences","place":["Srinagar, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biswajyoti","family":"Borkakoty","sequence":"additional","affiliation":[{"name":"Regional Medical Research Centre (ICMR)","place":["Dibrugarh, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"ofaf164","DOI":"10.1093\/OFID\/OFAF164","article-title":"Whole genome sequencing analysis of Klebsiella pneumoniae isolates from health care\u2013associated bacteremia of urinary origin in Spain: findings from the multicenter ITUBRAS-2 cohort study","volume":"12","author":"Becerra-Aparicio","year":"2025","journal-title":"Open Forum Infect. Dis."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/BIOINFORMATICS\/BTU170","article-title":"Trimmomatic: a flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.3389\/FMICB.2012.00110","article-title":"CTX-M enzymes: origin and diffusion","volume":"3","author":"Cant\u00f3n","year":"2012","journal-title":"Front. Microbiol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"2227","DOI":"10.1128\/AAC.01707-08","article-title":"Resistance plasmid families in Enterobacteriaceae","volume":"53","author":"Carattoli","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"3895","DOI":"10.1128\/AAC.02412-14","article-title":"In silico detection and typing of plasmids using PlasmidFinder and plasmid multilocus sequence typing","volume":"58","author":"Carattoli","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.3389\/FMICB.2021.750662","article-title":"Clinical epidemiology, risk factors, and control strategies of Klebsiella pneumoniae infection","volume":"12","author":"Chang","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"644","DOI":"10.25259\/IJMR_1915_22","article-title":"Characterization of blaOXA-232 carrying carbapenem-resistant Klebsiella pneumoniae (CRKP) & their expression profiles under selective carbapenem pressure: an in-depth study from India","volume":"159","author":"Das","year":"2024","journal-title":"Indian J. Med. Res."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1919","DOI":"10.1038\/S41564-019-0492-8","article-title":"Epidemic of carbapenem-resistant Klebsiella pneumoniae in Europe is driven by nosocomial spread","volume":"4","author":"David","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"e1010334","DOI":"10.1371\/JOURNAL.PPAT.1010334","article-title":"Widespread emergence of OmpK36 loop 3 insertions among multidrug-resistant clones of Klebsiella pneumoniae","volume":"18","author":"David","year":"2022","journal-title":"PLoS Pathog."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"163","DOI":"10.3201\/EID2001.130904","article-title":"Co-production of NDM-1 and OXA-232 by Klebsiella pneumoniae","volume":"20","author":"Doi","year":"2014","journal-title":"Emerg. Infect. 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Microbiol."},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1128\/MICROBIOLSPEC.PLAS-0006-2013","article-title":"Plasmid-mediated quinolone resistance","volume":"2","author":"Jacoby","year":"2014","journal-title":"Microbiol. 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Microbiol."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"e0177921","DOI":"10.1128\/SPECTRUM.01779-21","article-title":"In vitro evolution of Cefiderocol resistance in an NDM-producing Klebsiella pneumoniae due to functional loss of CirA","volume":"9","author":"McElheny","year":"2021","journal-title":"Microbiol. Spectrum"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"107131","DOI":"10.1016\/j.ijantimicag.2024.107131","article-title":"Characterisation of cefiderocol-resistant spontaneous mutant variants of Klebsiella pneumoniae-producing NDM-5 with a single mutation in cirA","volume":"63","author":"Mezcord","year":"2024","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1093\/FEMSRE\/FUX013","article-title":"Klebsiella pneumoniae: a major worldwide source and shuttle for antibiotic resistance","volume":"41","author":"Navon-Venezia","year":"2017","journal-title":"FEMS Microbiol. Rev."},{"key":"ref30","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":"Bioinformatics"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"e000056","DOI":"10.1099\/MGEN.0.000056","article-title":"SNP-sites: rapid efficient extraction of SNPs from multi-FASTA alignments","volume":"2","author":"Page","year":"2016","journal-title":"Microb. Genom."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"5873","DOI":"10.1128\/AAC.01019-15","article-title":"Carbapenemase-producing Klebsiella pneumoniae, a key pathogen set for global nosocomial dominance","volume":"59","author":"Pitout","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"e00376\u201322","DOI":"10.1128\/SPECTRUM.00376-22","article-title":"Comparative analysis of clinical and genomic characteristics of Hypervirulent Klebsiella pneumoniae from hospital and community settings: experience from a tertiary healthcare Center in India","volume":"10","author":"Raj","year":"2022","journal-title":"Microbiol. Spectrum"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"10441","DOI":"10.1038\/s41598-022-14547-6","article-title":"Common and distinctive genomic features of Klebsiella pneumoniae thriving in the natural environment or in clinical settings","volume":"12","author":"Rocha","year":"2022","journal-title":"Sci. Rep."},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00001-19","article-title":"Hypervirulent Klebsiella pneumoniae","volume":"32","author":"Russo","year":"2019","journal-title":"Clin. Microbiol. Rev."},{"key":"ref36","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":"Bioinformatics"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"001271","DOI":"10.1099\/MGEN.0.001271","article-title":"Geographical distribution, disease association and diversity of Klebsiella pneumoniae K\/L and O antigens in India: roadmap for vaccine development","volume":"10","author":"Shamanna","year":"2024","journal-title":"Microb. Genom."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1186\/S12866-019-1513-8","article-title":"Rapidly disseminating blaOXA-232 carrying Klebsiella pneumoniae belonging to ST231 in India: multiple and varied mobile genetic elements","volume":"19","author":"Shankar","year":"2019","journal-title":"BMC Microbiol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1186\/S12879-024-10012-Z","article-title":"Genotypic diversity and virulence factors of Klebsiella pneumoniae in a north Indian tertiary care hospital","volume":"24","author":"Sharma","year":"2024","journal-title":"BMC Infect. Dis."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.1128\/AAC.01275-10","article-title":"Klebsiella pneumoniae outer membrane porins OmpK35 and OmpK36 play roles in both antimicrobial resistance and virulence","volume":"55","author":"Tsai","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1186\/s12864-024-10139-y","article-title":"Exploring the resistome, virulome, and mobilome of multidrug-resistant Klebsiella pneumoniae isolates: deciphering the molecular basis of carbapenem resistance","volume":"25","author":"Ullah","year":"2024","journal-title":"BMC Genomics"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1080\/20477724.2017.1340128","article-title":"Carbapenem resistant Klebsiella pneumoniae isolated from bloodstream infection: Indian experience","volume":"111","author":"Veeraraghavan","year":"2017","journal-title":"Pathog. Glob. Health"},{"key":"ref43","first-page":"1","year":"2024"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"e1005595","DOI":"10.1371\/JOURNAL.PCBI.1005595","article-title":"Unicycler: resolving bacterial genome assemblies from short and long sequencing reads","volume":"13","author":"Wick","year":"2017","journal-title":"PLoS Comput. Biol."},{"key":"ref45","doi-asserted-by":"publisher","DOI":"10.1093\/MOLBEV\/MSAG117","article-title":"IQ-TREE 3: phylogenomic inference software using complex evolutionary models","volume":"43","author":"Wong","year":"2026","journal-title":"Mol. Biol. Evol."},{"key":"ref46","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":"ref47","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1101\/GR.232397.117","article-title":"Grapetree: visualization of core genomic relationships among 100,000 bacterial pathogens","volume":"28","author":"Zhou","year":"2018","journal-title":"Genome Res."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1831365\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:44:18Z","timestamp":1790228658000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1831365\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":47,"alternative-id":["10.3389\/fmicb.2026.1831365"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2026.1831365","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,24]]},"article-number":"1831365"}}