{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:36:34Z","timestamp":1774312594171,"version":"3.50.1"},"reference-count":110,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The <jats:italic>Klebsiella pneumoniae<\/jats:italic> (KP) species complex (KpSC) comprises KP as the predominant species, and six other taxa including two subspecies each of <jats:italic>Klebsiella<\/jats:italic> var<jats:italic>iicola<\/jats:italic> (KV) and <jats:italic>Klebsiella quasipneumoniae<\/jats:italic> (KQ), all capable of causing clinical infections and often challenging to differentiate. Among these, KP is by far the most clinically significant, with the emergence of multidrug-resistant and hypervirulent strains leading to severe infections and limited treatment options, underscoring the need to understand the genomic features of KP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study compared globally disseminated KP lineages with less abundant KV strains in synthetic human urine (SHU) across multiple omics levels to identify characteristics differentiating these closely related species. Moreover, a large genomic dataset of over 6,000 publicly available genomes of KP, KV, and KQ was constructed for comparisons to other members of the KpSC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among eight clinical KP strains representing four different sequence types (STs), we identified 107 genes comprising the KP-specific core genome, while these genes were absent from two selected KV genomes. Transcriptome and proteome analyses in SHU revealed different regulatory patterns between KP and KV strains, with metabolic responses playing a pivotal role. A total of 193 genes specific to the investigated KP STs were identified, exhibiting differential expression at the transcriptomic and\/or proteomic levels. Comparison to the genomic dataset highlighted genes adaptively regulated or uniquely present in KP genomes. For example, certain genes for citrate metabolism are uniquely upregulated in KP and a gene cluster for the cellobiose phosphotransferase system, previously linked to bacterial virulence and biofilm formation, was found exclusively in KP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our study underscores the metabolic flexibility of KP strains in response to specific environmental conditions, potentially contributing to opportunistic pathogenicity. We identified markers enriched in KP STs, providing a foundation for future investigations including their relevance for diagnostics.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2025.1657680","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T05:32:33Z","timestamp":1755667953000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Multi-omics investigation reveals unique markers in Klebsiella pneumoniae compared to closely related species"],"prefix":"10.3389","volume":"16","author":[{"given":"Lena-Sophie","family":"Swiatek","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin","family":"Surmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elias","family":"Eger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justus U.","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Gesell Salazar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan E.","family":"Heiden","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guido","family":"Werner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nils-Olaf","family":"H\u00fcbner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen A.","family":"Bohnert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karsten","family":"Becker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uwe","family":"V\u00f6lker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Schwabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Schaufler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"105861","DOI":"10.1016\/j.mimet.2020.105861","article-title":"Evaluation of pooled human urine and synthetic alternatives in a dynamic bladder infection in vitro model simulating oral fosfomycin therapy","volume":"171","author":"Abbott","year":"2020","journal-title":"J. Microbiol. Methods"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"e1004601","DOI":"10.1371\/journal.ppat.1004601","article-title":"Preferential use of central metabolism in vivo reveals a nutritional basis for Polymicrobial infection","volume":"11","author":"Alteri","year":"2015","journal-title":"PLoS Pathog."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.mib.2011.12.004","article-title":"Escherichia coli physiology and metabolism dictates adaptation to diverse host microenvironments","volume":"15","author":"Alteri","year":"2012","journal-title":"Curr. Opin. Microbiol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e00775","DOI":"10.1128\/mBio.00775-15","article-title":"Genome-wide identification of Klebsiella pneumoniae fitness genes during lung infection","volume":"6","author":"Bachman","year":"2015","journal-title":"MBio"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13756-018-0352-y","article-title":"Genome-based analysis of Carbapenemase-producing Klebsiella pneumoniae isolates from German hospital patients, 2008-2014","volume":"7","author":"Becker","year":"2018","journal-title":"Antimicrob Resist Infect Control"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1812","DOI":"10.3201\/eid2011.140206","article-title":"Genomic definition of hypervirulent and multidrug-resistant Klebsiella pneumoniae clonal groups","volume":"20","author":"Bialek-Davenet","year":"2014","journal-title":"Emerg. Infect. Dis."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e1900192","DOI":"10.1002\/pmic.201900192","article-title":"Improving proteome coverage for small sample amounts: an advanced method for proteomics approaches with low bacterial cell numbers","volume":"19","author":"Blankenburg","year":"2019","journal-title":"Proteomics"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1881","DOI":"10.1111\/1462-2920.13689","article-title":"Metabolic diversity of the emerging pathogenic lineages of Klebsiella pneumoniae","volume":"19","author":"Blin","year":"2017","journal-title":"Environ. Microbiol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"3146","DOI":"10.1099\/ijs.0.062737-0","article-title":"Description of Klebsiella quasipneumoniae sp. nov., isolated from human infections, with two subspecies, Klebsiella quasipneumoniae subsp. quasipneumoniae subsp. nov. and Klebsiella quasipneumoniae subsp. similipneumoniae subsp. nov., and demonstration that Klebsiella singaporensis is a junior heterotypic synonym of Klebsiella variicola","volume":"64","author":"Brisse","year":"2014","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1099\/00207713-51-3-915","article-title":"Phylogenetic diversity of Klebsiella pneumoniae and Klebsiella oxytoca clinical isolates revealed by randomly amplified polymorphic DNA, gyrA and parC genes sequencing and automated ribotyping","volume":"51","author":"Brisse","year":"2001","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"e943","DOI":"10.1016\/S2666-5247(23)00208-2","article-title":"Population structure and antimicrobial resistance among Klebsiella isolates sampled from human, animal, and environmental sources in Ghana: a cross-sectional genomic one health study","volume":"4","author":"Calland","year":"2023","journal-title":"The Lancet Microbe"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"e0197021","DOI":"10.1128\/spectrum.01970-21","article-title":"Association between timing of colonization and risk of developing Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae infection in hospitalized patients","volume":"10","author":"Cano","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"ref13","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":"ref14","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/S0732-8893(00)00157-7","article-title":"Klebsiella pneumoniae isolates causing liver abscess in Taiwan","volume":"37","author":"Chang","year":"2000","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1","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":"ref16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2180-9-168","article-title":"Genomic diversity of citrate fermentation in Klebsiella pneumoniae","volume":"9","author":"Chen","year":"2009","journal-title":"BMC Microbiol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1038\/nchembio.2007.24","article-title":"Targeting virulence: a new paradigm for antimicrobial therapy","volume":"3","author":"Clatworthy","year":"2007","journal-title":"Nat. Chem. Biol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"D523","DOI":"10.1093\/nar\/gkac1052","article-title":"UniProt: the universal protein knowledgebase in 2023","volume":"51","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1093\/infdis\/130.4.402","article-title":"Prevalence and characteristics of Klebsiella species: relation to association with a hospital environment","volume":"130","author":"Davis","year":"1974","journal-title":"J. Infect. Dis."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/antibiotics10030244","article-title":"High risk clone: a proposal of criteria adapted to the one health context with application to enterotoxigenic Escherichia coli in the pig population","volume":"10","author":"de Lagarde","year":"2021","journal-title":"Antibiotics"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1762","DOI":"10.21105\/joss.01762","article-title":"Mashtree: a rapid comparison of whole genome sequence files","volume":"4","author":"Den Bakker","year":"2022","journal-title":"J. Open Source Soft."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"4178","DOI":"10.1128\/JCM.43.8.4178\u20134182.2005","article-title":"Multilocus sequence typing of Klebsiella pneumoniae nosocomial isolates","volume":"43","author":"Diancourt","year":"2005","journal-title":"J. Clin. Microbiol."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/nrd.2017.23","article-title":"Different drugs for bad bugs: Antivirulence strategies in the age of antibiotic resistance","volume":"16","author":"Dickey","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"3023","DOI":"10.2900\/993023","article-title":"Emergence of hypervirulent K lebsiella pneum oniae ST23 carrying carbapenemase genes in EU \/ EEA countries event background urgent inquiry and data request to EURGen-net","volume":"14","year":"2024","journal-title":"Eur. Cent. Dis. Prev. Control"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/nrmicro3432","article-title":"Urinary tract infections: epidemiology, mechanisms of infection and treatment options","volume":"13","author":"Flores-Mireles","year":"2015","journal-title":"Nat. Rev. Microbiol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1007\/BF01880516","article-title":"Ueber die Schizomyceten bei der acuten fibr sen","volume":"87","author":"Friedl\u00e4nder","year":"1882","journal-title":"Arch. Pathol. Anat. und Physiol. und Klin. Med."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"3150","DOI":"10.1093\/bioinformatics\/bts565","article-title":"Bioinformatics applications note sequence analysis CD-HIT: accelerated for clustering the next-generation sequencing data","volume":"28","author":"Fu","year":"2012","journal-title":"Bioinforma. Apllications Note"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1178","DOI":"10.1016\/j.bbabio.2014.01.016","article-title":"Cytochrome bd oxidase and bacterial tolerance to oxidative and nitrosative stress","volume":"1837","author":"Giuffr\u00e8","year":"2014","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1093\/cid\/cix270","article-title":"Gastrointestinal carriage is a major reservoir of Klebsiella pneumoniae infection in intensive care patients","volume":"65","author":"Gorrie","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"3017","DOI":"10.1038\/s41467-022-30717-6","article-title":"Genomic dissection of Klebsiella pneumoniae infections in hospital patients reveals insights into an opportunistic pathogen","volume":"13","author":"Gorrie","year":"2022","journal-title":"Nat. Commun."},{"key":"ref31","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":"ref32","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1186\/s13073-020-00814-6","article-title":"A Klebsiella pneumoniae ST307 outbreak clone from Germany demonstrates features of extensive drug resistance, hypermucoviscosity, and enhanced iron acquisition","volume":"12","author":"Heiden","year":"2020","journal-title":"Genome Med."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"E3574","DOI":"10.1073\/pnas.1501049112","article-title":"Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae, an urgent threat to public health","volume":"112","author":"Holt","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1128\/iai.00206-22","article-title":"Klebsiella pneumoniae L-fucose metabolism promotes gastrointestinal colonization and modulates its virulence determinants","volume":"67","author":"Hudson","year":"2022","journal-title":"Infect. Immun."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"D309","DOI":"10.1093\/nar\/gky1085","article-title":"eggNOG 5.0: a hierarchical, functionally and phylogenetically annotated orthology resource based on 5090 organisms and 2502 viruses","volume":"47","author":"Huerta-Cepas","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12879-019-4498-x","article-title":"Clinical characteristics in blood stream infections caused by Klebsiella pneumoniae, Klebsiella variicola, and Klebsiella quasipneumoniae: a comparative study, Japan, 2014-2017","volume":"19","author":"Imai","year":"2019","journal-title":"BMC Infect. Dis."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.mimet.2016.06.013","article-title":"Evaluation of the in vitro growth of urinary tract infection-causing gram-negative and gram-positive bacteria in a proposed synthetic human urine (SHU) medium","volume":"127","author":"Ipe","year":"2016","journal-title":"J. Microbiol. Methods"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2164-15-54","article-title":"Comparative analysis of the complete genome of KPC-2-producing Klebsiella pneumoniae Kp13 reveals remarkable genome plasticity and a wide repertoire of virulence and resistance mechanisms","volume":"15","author":"Ivan","year":"2014","journal-title":"BMC Genomics"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1002\/cmdc.201600006.Antivirulence","article-title":"Antivirulence Isoquinolone Mannosides: optimization of the Biaryl Aglycone for FimH lectin binding affinity and efficacy in the treatment of chronic UTI","volume":"11","author":"Jarvisa","year":"2016","journal-title":"Chem. Med. Chem."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.3390\/microorganisms9061282","article-title":"From Klebsiella pneumoniae colonization to dissemination: an overview of studies implementing murine models","volume":"9","author":"Joseph","year":"2021","journal-title":"Microorganisms"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"D587","DOI":"10.1093\/nar\/gkac963","article-title":"KEGG for taxonomy-based analysis of pathways and genomes","volume":"51","author":"Kanehisa","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/j.tim.2011.04.003","article-title":"Are pathogenic bacteria just looking for food? Metabolism and microbial pathogenesis","volume":"19","author":"Kinsella","year":"2011","journal-title":"Trends Microbiol."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1007\/BF01641355","article-title":"Transferable resistance to cefotaxime, cefoxitin, cefamandole and cefuroxime in clinical isolates of Klebsiella pneumoniae and Serratia marcescens","volume":"11","author":"Knothe","year":"1983","journal-title":"Infection"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"160","DOI":"10.3201\/eid0802.010025","article-title":"Community-acquired Klebsiella pneumoniae bacteremia: global differences in clinical patterns","volume":"8","author":"Ko","year":"2002","journal-title":"Emerg. Infect. Dis."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1186\/s12879-022-07558-1","article-title":"Genomic surveillance for multidrug-resistant or hypervirulent Klebsiella pneumoniae among United States bloodstream isolates","volume":"22","author":"Kochan","year":"2022","journal-title":"BMC Infect. Dis."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1038\/s41587-019-0072-8","article-title":"Assembly of long, error-prone reads using repeat graphs","volume":"37","author":"Kolmogorov","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12917-017-1093-5","article-title":"Whole genome sequencing of an ExPEC that caused fatal pneumonia at a pig farm in Changchun, China","volume":"13","author":"Kong","year":"2017","journal-title":"BMC Vet Res"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1021\/cb100096f","article-title":"Antifolate-induced depletion of intracellular glycine and purines inhibits thymineless death in E. coli","volume":"5","author":"Kwon","year":"2010","journal-title":"ACS Chem. Biol."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"4188","DOI":"10.1038\/s41467-021-24448-3","article-title":"A genomic surveillance framework and genotyping tool for Klebsiella pneumoniae and its related species complex","volume":"12","author":"Lam","year":"2021","journal-title":"Nat. Commun."},{"key":"ref50","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":"ref51","doi-asserted-by":"publisher","first-page":"104429","DOI":"10.1016\/j.ebiom.2022.104429","article-title":"Pathogen-associated gene discovery workflows for novel antivirulence therapeutic development","volume":"88","author":"Lau","year":"2023","journal-title":"EBioMedicine"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1186\/1471-2105-12-124","article-title":"Proteinortho: detection of (co-) orthologs in large-scale analysis","volume":"12","author":"Lechner","year":"2011","journal-title":"BMC Bioinformatics"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1093\/cid\/cit675","article-title":"Increasing occurrence of antimicrobial- resistant Hypervirulent (Hypermucoviscous) Klebsiella pneumoniae isolates in China","volume":"58","author":"Li","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"FeatureCounts: an efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1056\/NEJMoa0907635","article-title":"Treatment with monoclonal antibodies against Clostridium difficile toxins","volume":"365","author":"Lowy","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"3001","DOI":"10.1093\/jac\/dky301","article-title":"Occurrence of colistin-resistant hypervirulent Klebsiella variicola","volume":"73","author":"Lu","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1056\/NEJMoa1306801","article-title":"Multistate point-prevalence survey of health care\u2013associated infections","volume":"370","author":"Magill","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fcimb.2018.00004","article-title":"Colonization, infection, and the accessory genome of Klebsiella pneumoniae","volume":"8","author":"Martin","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/bs.aambs.2014.09.002","article-title":"Escherichia coli ST131: the quintessential example of anInternational multiresistant high-risk clone","volume":"90","author":"Mathers","year":"2015","journal-title":"Adv. Appl. Microbiol."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.jgar.2023.08.009","article-title":"Prevalence, clonal diversity, and antimicrobial resistance of hypervirulent Klebsiella pneumoniae and Klebsiella variicola clinical isolates in northern Japan","volume":"35","author":"Matsuda","year":"2023","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"416","DOI":"10.3390\/microorganisms10020416","article-title":"Whole-genome sequencing enables molecular characterization of non-clonal group 258 high-risk clones (ST13, ST17, ST147 and ST307) among Carbapenem-resistant Klebsiella pneumoniae from a tertiary University Hospital Centre in Portugal","volume":"10","author":"Mendes","year":"2022","journal-title":"Microorganisms"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"5248","DOI":"10.1128\/JB.183.18.5248-5256.2001","article-title":"Catabolite repression of the citrate fermentation genes in Klebsiella pneumoniae: evidence for involvement of the cyclic AMP receptor protein","volume":"183","author":"Meyer","year":"2001","journal-title":"J. Bacteriol."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"4896","DOI":"10.1021\/acs.jproteome.4c00286","article-title":"Metabolic reprogramming of Klebsiella pneumoniae exposed to serum and its potential implications in host immune system evasion and resistance","volume":"23","author":"Moraes","year":"2024","journal-title":"J. Proteome Res."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"1530","DOI":"10.1038\/s41467-023-37200-w","article-title":"Integrative omics identifies conserved and pathogen-specific responses of sepsis-causing bacteria","volume":"14","author":"Mu","year":"2023","journal-title":"Nat. Commun."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1016\/j.chembiol.2014.08.020","article-title":"Targeting bacterial central metabolism for drug development","volume":"21","author":"Murima","year":"2014","journal-title":"Chem. Biol."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/S0140-6736(21)02724-0","article-title":"Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis","volume":"399","author":"Murray","year":"2022","journal-title":"Lancet"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1126\/science.1206848","article-title":"Condition-dependent transcriptome reveals high-level regulatory architecture in Bacillus subtilis","volume":"335","author":"Nicolas","year":"2012","journal-title":"Science"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/S1473-3099(09)70054-4","article-title":"The real threat of Klebsiella pneumoniae carbapenemase","volume":"9","author":"Nordmann","year":"2009","journal-title":"Lancet Infect. Dis."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"100970","DOI":"10.1016\/j.onehlt.2025.100970","article-title":"Subtle genomic differences in Klebsiella pneumoniae sensu stricto isolates indicate host adaptation","volume":"20","author":"O\u2019Brien","year":"2025","journal-title":"One Heal."},{"key":"ref70","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fmicb.2019.03084","article-title":"The progress of multi-omics technologies: determining function in lactic acid bacteria using a systems level approach","volume":"10","author":"O\u2019Donnell","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/antibiotics11111613","article-title":"Exploring the antibiotic resistance profile of clinical Klebsiella pneumoniae isolates in Portugal","volume":"11","author":"Oliveira","year":"2022","journal-title":"Antibiotics"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1128\/MMBR.00078-15","article-title":"Klebsiella pneumoniae: going on the offense with a strong Defens","volume":"80","author":"Paczosa","year":"2016","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"D442","DOI":"10.1093\/nar\/gky1106","article-title":"The PRIDE database and related tools and resources in 2019: improving support for quantification data","volume":"47","author":"Perez-Riverol","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1128\/cmr.11.4.589","article-title":"Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors","volume":"11","author":"Podschun","year":"1998","journal-title":"Clin. Microbiol. 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Rep."},{"key":"ref78","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/pmic.202300294","article-title":"Massspecpreppy \u2014 an end-to-end solution for automated protein concentration determination and flexible sample digestion for proteomics applications","volume":"24","author":"Reder","year":"2023","journal-title":"Proteomics"},{"key":"ref79","doi-asserted-by":"publisher","first-page":"39189","DOI":"10.1074\/jbc.M305864200","article-title":"The structure of the periplasmic ligand-binding domain of the sensor kinase CitA reveals the first extracellular pas domain","volume":"278","author":"Reinelt","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"5876","DOI":"10.1038\/s41598-024-55546-z","article-title":"Comprehensive study reveals phenotypic heterogeneity in Klebsiella pneumoniae species complex isolates","volume":"14","author":"Rodr\u00edguez-Medina","year":"2024","journal-title":"Sci. Rep."},{"key":"ref81","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1078\/0723-2020-00261","article-title":"Klebsiella variicola, a novel species with clinical and plant-associated isolates","volume":"27","author":"Rosenblueth","year":"2004","journal-title":"Syst. Appl. Microbiol."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.nmni.2015.06.005","article-title":"The bacterial pangenome as a new tool for analysing pathogenic bacteria","volume":"7","author":"Rouli","year":"2015","journal-title":"New Microbes New Infect."},{"key":"ref83","doi-asserted-by":"publisher","first-page":"4427","DOI":"10.1128\/JB.00103-09","article-title":"A metabolic operon in extraintestinal pathogenic Escherichia coli promotes fitness under stressful conditions and invasion of eukaryotic cells","volume":"191","author":"Rouquet","year":"2009","journal-title":"J. Bacteriol."},{"key":"ref84","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/978-1-0716-1024-4_8","article-title":"Quantitative mass spectrometry-based proteomics: an overview","volume":"2228","author":"Rozanova","year":"2021","journal-title":"Methods Mol. Biol."},{"key":"ref85","doi-asserted-by":"publisher","first-page":"e00776","DOI":"10.1128\/jcm.00776-18","article-title":"Identification of biomarkers for differentiation of Hypervirulent Klebsiella pneumoniae from Classical K. pneumoniae","volume":"56","author":"Russo","year":"2018","journal-title":"J. Clin. Microbiol."},{"key":"ref86","doi-asserted-by":"publisher","first-page":"20159","DOI":"10.1038\/s41598-019-56693-4","article-title":"A new artificial urine protocol to better imitate human urine","volume":"9","author":"Sarigul","year":"2019","journal-title":"Sci. Rep."},{"key":"ref87","doi-asserted-by":"publisher","first-page":"D20","DOI":"10.1093\/nar\/gkab1112","article-title":"Database resources of the national center for biotechnology information","volume":"50","author":"Sayers","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref88","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1128\/jb.99.2.422-433.1969","article-title":"Taxonomic investigations on expressed and cryptic phospho-beta-glucosidases in Enterobacteriaceae","volume":"99","author":"Schaefler","year":"1969","journal-title":"J. Bacteriol."},{"key":"ref89","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1080\/22221751.2023.2271096","article-title":"Convergent Klebsiella pneumoniae strains belonging to a sequence type 307 outbreak clone combine cefiderocol and carbapenem resistance with hypervirulence","volume":"12","author":"Schaufler","year":"2023","journal-title":"Emerg. Microbes Infect."},{"key":"ref90","doi-asserted-by":"publisher","first-page":"5993","DOI":"10.1128\/IAI.72.10.5993-6001.2004","article-title":"The pathogenicity island-associated K15 capsule determinant exhibits a novel genetic structure and correlates with virulence in uropathogenic Escherichia coli strain 536","volume":"72","author":"Schneider","year":"2004","journal-title":"Infect. Immun."},{"key":"ref91","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":"ref92","doi-asserted-by":"publisher","first-page":"107","DOI":"10.4161\/viru.22718","article-title":"Hypervirulent (hypermucoviscous) Klebsiella pneumoniae","volume":"4","author":"Shon","year":"2013","journal-title":"Virulence"},{"key":"ref93","doi-asserted-by":"publisher","first-page":"3442","DOI":"10.1093\/nar\/28.18.3442","article-title":"String: a web-server to retrieve and display the repeatedly occurring neighbourhood of a gene","volume":"28","author":"Snel","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref94","doi-asserted-by":"publisher","first-page":"5869","DOI":"10.1038\/s41598-017-05949-y","article-title":"Enhanced differential expression statistics for data-independent acquisition proteomics","volume":"7","author":"Suomi","year":"2017","journal-title":"Sci. Rep."},{"key":"ref95","doi-asserted-by":"publisher","first-page":"10800","DOI":"10.1093\/nar\/gkab835","article-title":"Erratum: the STRING database in 2021: customizable protein\u2013protein networks, and functional characterization of user-uploaded gene\/measurement sets (nucleic acids research)","volume":"49","author":"Szklarczyk","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref96","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/S1473-3099(17)30753-3","article-title":"Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis","volume":"18","author":"Tacconelli","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref97","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1016\/j.mib.2008.09.006","article-title":"Comparative genomics: the bacterial pan-genome","volume":"11","author":"Tettelin","year":"2008","journal-title":"Curr. Opin. Microbiol."},{"key":"ref98","doi-asserted-by":"publisher","first-page":"2054","DOI":"10.1038\/s41564-022-01263-0","article-title":"A large-scale genomic snapshot of Klebsiella spp. isolates in northern Italy reveals limited transmission between clinical and non-clinical settings","volume":"7","author":"Thorpe","year":"2022","journal-title":"Nat. Microbiol."},{"key":"ref99","doi-asserted-by":"publisher","DOI":"10.1038\/s43588-021-00073-4","article-title":"Time- and memory-efficient genome assembly with Raven","author":"Vaser","year":"2021","journal-title":"Nat. Comput. Sci."},{"key":"ref100","doi-asserted-by":"publisher","first-page":"e1008010","DOI":"10.1371\/journal.ppat.1008010","article-title":"The Klebsiella pneumoniae citrate synthase gene, gltA, influences site specific fitness during infection","volume":"15","author":"Vornhagen","year":"2019","journal-title":"PLoS Pathog."},{"key":"ref101","doi-asserted-by":"publisher","first-page":"e1009802","DOI":"10.1371\/journal.pcbi.1009802","article-title":"PLOS COMPUTATIONAL BIOLOGY Polypolish: short-read polishing of long-read bacterial genome assemblies","volume":"18","author":"Wick","year":"2022","journal-title":"PLoS Comput. Biol."},{"key":"ref102","doi-asserted-by":"publisher","first-page":"1","DOI":"10.12688\/f100research.217824","article-title":"Benchmarking of long-read assemblers for prokaryote whole genome sequencing [version 4; peer review: 4 approved]","volume":"8","author":"Wick","year":"2023","journal-title":"F1000Res"},{"key":"ref103","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1186\/s13059-021-02483-z","article-title":"Trycycler: consensus long-read assemblies for bacterial genomes","volume":"22","author":"Wick","year":"2021","journal-title":"Genome Biol."},{"key":"ref104","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":"ref105","volume-title":"WHO bacterial priority pathogens list, 2024: bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance","year":"2024"},{"key":"ref106","doi-asserted-by":"publisher","first-page":"2464","DOI":"10.1128\/IAI.06247-11","article-title":"Cellobiose-specific phosphotransferase system of Klebsiella pneumoniae and its importance in biofilm formation and virulence","volume":"80","author":"Wu","year":"2012","journal-title":"Infect. Immun."},{"key":"ref107","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.mib.2018.04.004","article-title":"Klebsiella pneumoniae as a key trafficker of drug resistance genes from environmental to clinically important bacteria","volume":"45","author":"Wyres","year":"2018","journal-title":"Curr. Opin. Microbiol."},{"key":"ref108","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":"","journal-title":"Nat. Rev. Microbiol."},{"key":"ref109","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s13073-019-0706-y","article-title":"Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from south and Southeast Asia","volume":"12","author":"Wyres","year":"","journal-title":"Genome Med."},{"key":"ref110","doi-asserted-by":"publisher","first-page":"e1008114","DOI":"10.1371\/journal.pgen.1008114","article-title":"Distinct evolutionary dynamics of horizontal gene transfer in drug resistant and virulent clones of Klebsiella pneumoniae","volume":"15","author":"Wyres","year":"2019","journal-title":"PLoS Genet."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1657680\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T05:32:35Z","timestamp":1755667955000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1657680\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,20]]},"references-count":110,"alternative-id":["10.3389\/fmicb.2025.1657680"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2025.1657680","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,20]]},"article-number":"1657680"}}