{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:53:04Z","timestamp":1787500384860,"version":"build-2736575974"},"reference-count":114,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["DP200103364"],"award-info":[{"award-number":["DP200103364"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1176192"],"award-info":[{"award-number":["APP1176192"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosbiology.org"],"crossmark-restriction":false},"short-container-title":["PLoS Biol"],"abstract":"<jats:p>\n                    The\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    species complex inhabits a wide variety of hosts and environments, and is a major cause of antimicrobial resistant infections. Genomics has revealed the population comprises multiple species\/sub-species and hundreds of distinct co-circulating sub-lineage (SLs) that are associated with distinct gene complements. A substantial fraction of the pan-genome is predicted to be involved in metabolic functions and hence these data are consistent with metabolic differentiation at the SL level. However, this has so far remained unsubstantiated because in the past it was not possible to explore metabolic variation at scale. Here, we used a combination of comparative genomics and high-throughput genome-scale metabolic modeling to systematically explore metabolic diversity across the\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    species complex (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20097,835 genomes). We simulated growth outcomes for each isolate using carbon, nitrogen, phosphorus, and sulfur sources under aerobic and anaerobic conditions (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20091,278 conditions per isolate). We showed that the distributions of metabolic genes and growth capabilities are structured in the population, and confirmed that SLs exhibit unique metabolic profiles. In vitro co-culture experiments demonstrated reciprocal commensalistic cross-feeding between SLs, effectively extending the range of conditions supporting individual growth. We propose that these substrate specializations may promote the existence and persistence of co-circulating SLs by reducing nutrient competition and facilitating commensal interactions. Our findings have implications for understanding the eco-evolutionary dynamics of\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    and for the design of novel strategies to prevent opportunistic infections caused by this World Health Organization priority antimicrobial resistant pathogen.\n                  <\/jats:p>","DOI":"10.1371\/journal.pbio.3003559","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T18:31:14Z","timestamp":1765564274000},"page":"e3003559","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["A metabolic atlas of the Klebsiella pneumoniae species complex reveals lineage-specific metabolism and capacity for intra-species co-operation"],"prefix":"10.1371","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4224-2537","authenticated-orcid":true,"given":"Ben","family":"Vezina","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7096-0010","authenticated-orcid":true,"given":"Helena B.","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher K.","family":"Barlow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6653-1786","authenticated-orcid":true,"given":"Martin","family":"Rethoret-Pasty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2516-2108","authenticated-orcid":true,"given":"Sylvain","family":"Brisse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3895-8949","authenticated-orcid":true,"given":"Jonathan M.","family":"Monk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3949-2471","authenticated-orcid":true,"given":"Kathryn E.","family":"Holt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4033-6639","authenticated-orcid":true,"given":"Kelly L.","family":"Wyres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"issue":"10459","key":"pbio.3003559.ref001","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/S0140-6736(24)01867-1","article-title":"Global burden of bacterial antimicrobial resistance 1990-2021: a systematic analysis with forecasts to 2050","volume":"404","author":"GBD 2021 Antimicrobial Resistance Collaborators","year":"2024","journal-title":"Lancet"},{"issue":"9","key":"pbio.3003559.ref002","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/S1473-3099(25)00118-5","article-title":"The WHO Bacterial Priority Pathogens List 2024: a prioritisation study to guide research, development, and public health strategies against antimicrobial resistance","volume":"25","author":"H Sati","year":"2025","journal-title":"Lancet Infect Dis"},{"issue":"6","key":"pbio.3003559.ref003","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/s41579-019-0315-1","article-title":"Population genomics of Klebsiella pneumoniae","volume":"18","author":"KL Wyres","year":"2020","journal-title":"Nat Rev Microbiol"},{"issue":"27","key":"pbio.3003559.ref004","article-title":"Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae, an urgent threat to public health","volume":"112","author":"KE Holt","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pbio.3003559.ref005","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.2217\/fmb-2016-0079","article-title":"Metabolic competition as a driver of bacterial population structure","volume":"11","author":"ER Watkins","year":"2016","journal-title":"Future Microbiol"},{"issue":"6","key":"pbio.3003559.ref006","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1093\/molbev\/msv009","article-title":"Epidemic clones, oceanic gene pools, and Eco-LD in the free living marine pathogen Vibrio parahaemolyticus","volume":"32","author":"Y Cui","year":"2015","journal-title":"Mol Biol Evol"},{"issue":"3","key":"pbio.3003559.ref007","article-title":"Directional gene flow and ecological separation in Yersinia enterocolitica","volume":"1","author":"S Reuter","year":"2015","journal-title":"Microb Genom"},{"issue":"10","key":"pbio.3003559.ref008","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1111\/mec.12742","article-title":"Cryptic ecology among host generalist Campylobacter jejuni in domestic animals","volume":"23","author":"SK Sheppard","year":"2014","journal-title":"Mol Ecol"},{"issue":"9","key":"pbio.3003559.ref009","article-title":"Functional characterization of a gene cluster responsible for inositol catabolism associated with hospital-adapted isolates of Enterococcus faecium","volume":"167","author":"J Top","year":"2021","journal-title":"Microbiology (Reading)"},{"issue":"10","key":"pbio.3003559.ref010","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3002329","article-title":"Multidrug-resistant E. coli encoding high genetic diversity in carbohydrate metabolism genes displace commensal E. coli from the intestinal tract","volume":"21","author":"CH Connor","year":"2023","journal-title":"PLoS Biol"},{"issue":"2","key":"pbio.3003559.ref011","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/nrg3643","article-title":"Constraint-based models predict metabolic and associated cellular functions","volume":"15","author":"A Bordbar","year":"2014","journal-title":"Nat Rev Genet"},{"key":"pbio.3003559.ref012","article-title":"Pangenome reconstruction of Lactobacillaceae metabolism predicts species-specific metabolic traits","author":"A Omid","year":"2023","journal-title":"bioRxiv"},{"issue":"1","key":"pbio.3003559.ref013","doi-asserted-by":"crossref","first-page":"3771","DOI":"10.1038\/s41467-018-06112-5","article-title":"Genome-scale metabolic reconstructions of multiple Salmonella strains reveal serovar-specific metabolic traits","volume":"9","author":"Y Seif","year":"2018","journal-title":"Nat Commun"},{"issue":"8","key":"pbio.3003559.ref014","doi-asserted-by":"crossref","first-page":"7091","DOI":"10.3390\/ijms24087091","article-title":"New insights on metabolic features of Bacillus subtilis based on multistrain genome-scale metabolic modeling","volume":"24","author":"B Bl\u00e1zquez","year":"2023","journal-title":"Int J Mol Sci"},{"key":"pbio.3003559.ref015","doi-asserted-by":"crossref","first-page":"161","DOI":"10.3389\/fcimb.2019.00161","article-title":"Comparative genome-scale metabolic modeling of metallo-beta-lactamase-producing multidrug-resistant Klebsiella pneumoniae clinical isolates","volume":"9","author":"CJ Norsigian","year":"2019","journal-title":"Front Cell Infect Microbiol"},{"issue":"50","key":"pbio.3003559.ref016","doi-asserted-by":"crossref","first-page":"20338","DOI":"10.1073\/pnas.1307797110","article-title":"Genome-scale metabolic reconstructions of multiple Escherichia coli strains highlight strain-specific adaptations to nutritional environments","volume":"110","author":"JM Monk","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"26","key":"pbio.3003559.ref017","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.1523199113","article-title":"Comparative genome-scale modelling of Staphylococcus aureus strains identifies strain-specific metabolic capabilities linked to pathogenicity","volume":"113","author":"E Bosi","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"8","key":"pbio.3003559.ref018","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1038\/s41564-025-02056-x","article-title":"Integrative genomic reconstruction reveals heterogeneity in carbohydrate utilization across human gut bifidobacteria","volume":"10","author":"AA Arzamasov","year":"2025","journal-title":"Nat Microbiol"},{"key":"pbio.3003559.ref019","article-title":"A diverse genetic basis for metabolic reactions is revealed through pangenome analysis","author":"O Ardalani","year":"2025","journal-title":"bioRxiv"},{"issue":"11","key":"pbio.3003559.ref020","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.3201\/eid2011.140206","article-title":"Genomic definition of hypervirulent and multidrug-resistant Klebsiella pneumoniae clonal groups","volume":"20","author":"S Bialek-Davenet","year":"2014","journal-title":"Emerg Infect Dis"},{"key":"pbio.3003559.ref021","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","author":"M Wang","year":"2021","journal-title":"Lancet Infect Dis"},{"issue":"6","key":"pbio.3003559.ref022","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1093\/cid\/civ428","article-title":"Intermingled Klebsiella pneumoniae populations between retail meats and human urinary tract infections","volume":"61","author":"GS Davis","year":"2015","journal-title":"Clin Infect Dis"},{"issue":"1","key":"pbio.3003559.ref023","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1186\/s13059-019-1785-1","article-title":"Contrasting patterns of longitudinal population dynamics and antimicrobial resistance mechanisms in two priority bacterial pathogens over 7 years in a single center","volume":"20","author":"MJ Ellington","year":"2019","journal-title":"Genome Biol"},{"issue":"2","key":"pbio.3003559.ref024","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S1473-3099(16)30257-2","article-title":"Occurrence of carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in the European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE): a prospective, multinational study","volume":"17","author":"H Grundmann","year":"2017","journal-title":"Lancet Infect Dis"},{"issue":"2609","key":"pbio.3003559.ref025","article-title":"Exploring Klebsiella pneumoniae in healthy poultry reveals high genetic diversity, good biofilm-forming abilities and higher prevalence in Turkeys than broilers","volume":"12","author":"FV Franklin-Alming","year":"2021","journal-title":"Front Microbiol"},{"issue":"2","key":"pbio.3003559.ref026","doi-asserted-by":"crossref","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":"CL Gorrie","year":"2017","journal-title":"Clin Infect Dis"},{"issue":"5","key":"pbio.3003559.ref027","first-page":"1004","article-title":"A curated collection of Klebsiella metabolic models reveals variable substrate usage and gene essentiality","volume":"32","author":"J Hawkey","year":"2022","journal-title":"Genome Res"},{"issue":"7","key":"pbio.3003559.ref028","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.ijmm.2017.07.006","article-title":"Molecular epidemiology of Klebsiella pneumoniae invasive infections over a decade at Kilifi County Hospital in Kenya","volume":"307","author":"SP Henson","year":"2017","journal-title":"Int J Med Microbiol"},{"issue":"5","key":"pbio.3003559.ref029","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1080\/19490976.2020.1748257","article-title":"Klebsiella pneumoniae carriage in low-income countries: antimicrobial resistance, genomic diversity and risk factors","volume":"11","author":"B-T Huynh","year":"2020","journal-title":"Gut Microbes"},{"issue":"8","key":"pbio.3003559.ref030","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1093\/jac\/dkab118","article-title":"Characterization of Klebsiella pneumoniae complex isolates from pigs and humans in farms in Thailand: population genomic structure, antibiotic resistance and virulence genes","volume":"76","author":"T Leangapichart","year":"2021","journal-title":"J Antimicrob Chemother"},{"key":"pbio.3003559.ref031","doi-asserted-by":"crossref","first-page":"29316","DOI":"10.1038\/srep29316","article-title":"Differential host susceptibility and bacterial virulence factors driving Klebsiella liver abscess in an ethnically diverse population","volume":"6","author":"IR Lee","year":"2016","journal-title":"Sci Rep"},{"issue":"3","key":"pbio.3003559.ref032","first-page":"000778","article-title":"Genomic and antigenic diversity of colonizing Klebsiella pneumoniae isolates mirrors that of invasive isolates in Blantyre, Malawi","volume":"8","author":"JM Lewis","year":"2022","journal-title":"Microb Genom"},{"issue":"2","key":"pbio.3003559.ref033","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1093\/cid\/ciz174","article-title":"A One Health Study of the genetic relatedness of Klebsiella pneumoniae and their mobile elements in the east of England","volume":"70","author":"C Ludden","year":"2020","journal-title":"Clin Infect Dis"},{"key":"pbio.3003559.ref034","doi-asserted-by":"crossref","first-page":"103879","DOI":"10.1016\/j.resmic.2021.103879","article-title":"Novel strains of Klebsiella africana and Klebsiella pneumoniae in Australian fruit bats (Pteropus poliocephalus)","volume":"172","author":"FK McDougall","year":"2021","journal-title":"Res Microbiol"},{"issue":"5","key":"pbio.3003559.ref035","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1093\/jac\/dkz032","article-title":"Genomic analysis of Klebsiella pneumoniae isolates from Malawi reveals acquisition of multiple ESBL determinants across diverse lineages","volume":"74","author":"P Musicha","year":"2019","journal-title":"J Antimicrob Chemother"},{"issue":"6","key":"pbio.3003559.ref036","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.02481-18","article-title":"Population structure, antibiotic resistance, and uropathogenicity of Klebsiella variicola","volume":"9","author":"RF Potter","year":"2018","journal-title":"mBio"},{"issue":"1","key":"pbio.3003559.ref037","doi-asserted-by":"crossref","first-page":"1939599","DOI":"10.1080\/19490976.2021.1939599","article-title":"Gastrointestinal carriage of Klebsiella pneumoniae in a general adult population: a cross-sectional study of risk factors and bacterial genomic diversity","volume":"13","author":"N Raffelsberger","year":"2021","journal-title":"Gut Microbes"},{"issue":"1","key":"pbio.3003559.ref038","doi-asserted-by":"crossref","DOI":"10.1128\/spectrum.02376-21","article-title":"High prevalence of Klebsiella pneumoniae in European food products: a multicentric study comparing culture and molecular detection methods","volume":"10","author":"C Rodrigues","year":"2022","journal-title":"Microbiol Spectr"},{"key":"pbio.3003559.ref039","article-title":"Transmission dynamics of hyper-endemic multi-drug resistant Klebsiella pneumoniae in a Southeast Asian neonatal unit: a longitudinal study with whole genome sequencing","volume":"9","author":"PW Smit","year":"2018","journal-title":"Front Microbiol"},{"key":"pbio.3003559.ref040","article-title":"One health or three? Transmission modelling of Klebsiella isolates reveals ecological barriers to transmission between humans, animals and the environment","author":"H Thorpe","year":"2021","journal-title":"bioRxiv"},{"issue":"10","key":"pbio.3003559.ref041","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1093\/jac\/dkt180","article-title":"Predicting antimicrobial susceptibilities for Escherichia coli and Klebsiella pneumoniae isolates using whole genomic sequence data","volume":"68","author":"N Stoesser","year":"2013","journal-title":"J Antimicrob Chemother"},{"issue":"12","key":"pbio.3003559.ref042","doi-asserted-by":"crossref","first-page":"7347","DOI":"10.1128\/AAC.03900-14","article-title":"Genome sequencing of an extended series of NDM-producing Klebsiella pneumoniae isolates from neonatal infections in a Nepali hospital characterizes the extent of community- versus hospital-associated transmission in an endemic setting","volume":"58","author":"N Stoesser","year":"2014","journal-title":"Antimicrob Agents Chemother"},{"issue":"9","key":"pbio.3003559.ref043","doi-asserted-by":"crossref","first-page":"4425","DOI":"10.1111\/1462-2920.16047","article-title":"Transmission of Klebsiella strains and plasmids within and between grey-headed flying fox colonies","volume":"24","author":"B Vezina","year":"2022","journal-title":"Environ Microbiol"},{"issue":"7","key":"pbio.3003559.ref044","doi-asserted-by":"crossref","first-page":"3966","DOI":"10.1128\/AAC.05009-14","article-title":"Characterization of pre-antibiotic era Klebsiella pneumoniae isolates with respect to antibiotic\/disinfectant susceptibility and virulence in Galleria mellonella","volume":"59","author":"ME Wand","year":"2015","journal-title":"Antimicrob Agents Chemother"},{"issue":"1","key":"pbio.3003559.ref045","doi-asserted-by":"crossref","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":"KL Wyres","year":"2020","journal-title":"Genome Med"},{"key":"pbio.3003559.ref046","article-title":"Whole-genome analysis of Klebsiella pneumoniae from bovine mastitis milk in the U.S","author":"Z Zheng","year":"2021","journal-title":"Environ Microbiol"},{"key":"pbio.3003559.ref047","article-title":"enaBrowserTools","author":"European-Nucleotide-Archive","edition":"1"},{"key":"pbio.3003559.ref048","unstructured":"Krueger F. Trim Galore GitHub. 2012. Available from: https:\/\/github.com\/FelixKrueger\/TrimGalore"},{"issue":"6","key":"pbio.3003559.ref049","article-title":"Unicycler: resolving bacterial genome assemblies from short and long sequencing reads","volume":"13","author":"RR Wick","year":"2017","journal-title":"PLoS Comput Biol"},{"issue":"11","key":"pbio.3003559.ref050","first-page":"000685","article-title":"Bakta: rapid and standardized annotation of bacterial genomes via alignment-free sequence identification","volume":"7","author":"O Schwengers","year":"2021","journal-title":"Microb Genom"},{"issue":"1","key":"pbio.3003559.ref051","doi-asserted-by":"crossref","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":"MMC Lam","year":"2021","journal-title":"Nat Commun"},{"key":"pbio.3003559.ref052","doi-asserted-by":"crossref","DOI":"10.1093\/cid\/ciab784","article-title":"Rapid genomic characterization and global surveillance of Klebsiella using Pathogenwatch","volume":"73","author":"S Argim\u00f3n","year":"2021","journal-title":"Clin Infect Dis"},{"key":"pbio.3003559.ref053","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1186\/1471-2105-11-595","article-title":"BIGSdb: scalable analysis of bacterial genome variation at the population level","volume":"11","author":"KA Jolley","year":"2010","journal-title":"BMC Bioinformatics"},{"issue":"7","key":"pbio.3003559.ref054","doi-asserted-by":"crossref","DOI":"10.1093\/molbev\/msac135","article-title":"A dual barcoding approach to bacterial strain nomenclature: genomic taxonomy of Klebsiella pneumoniae strains","volume":"39","author":"M Hennart","year":"2022","journal-title":"Mol Biol Evol"},{"key":"pbio.3003559.ref055","article-title":"Bacterial strain nomenclature in the genomic era: Life Identification Numbers using a gene-by-gene approach","author":"F Palma","year":"2024","journal-title":"bioRxiv"},{"issue":"1","key":"pbio.3003559.ref056","doi-asserted-by":"crossref","first-page":"5114","DOI":"10.1038\/s41467-018-07641-9","article-title":"High throughput ANI analysis of 90K prokaryotic genomes reveals clear species boundaries","volume":"9","author":"C Jain","year":"2018","journal-title":"Nat Commun"},{"issue":"2","key":"pbio.3003559.ref057","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1101\/gr.241455.118","article-title":"Fast and flexible bacterial genomic epidemiology with PopPUNK","volume":"29","author":"JA Lees","year":"2019","journal-title":"Genome Res"},{"key":"pbio.3003559.ref058","volume-title":"Assembly Dereplicator","author":"RR Wick","year":"2019","edition":"0"},{"issue":"1","key":"pbio.3003559.ref059","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1186\/s13059-020-02090-4","article-title":"Producing polished prokaryotic pangenomes with the Panaroo pipeline","volume":"21","author":"G Tonkin-Hill","year":"2020","journal-title":"Genome Biol"},{"issue":"6","key":"pbio.3003559.ref060","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/S0168-9525(00)02024-2","article-title":"EMBOSS: the european molecular biology open software suite","volume":"16","author":"P Rice","year":"2000","journal-title":"Trend Genet"},{"issue":"1","key":"pbio.3003559.ref061","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: kyoto encyclopedia of genes and genomes","volume":"28","author":"M Kanehisa","year":"2000","journal-title":"Nucleic Acids Res"},{"issue":"7","key":"pbio.3003559.ref062","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1093\/bioinformatics\/btz859","article-title":"KofamKOALA: KEGG ortholog assignment based on profile HMM and adaptive score threshold","volume":"36","author":"T Aramaki","year":"2020","journal-title":"Bioinformatics"},{"key":"pbio.3003559.ref063","volume-title":"Vegan: community ecology package","author":"J Oksanen","year":"2020","edition":"2"},{"issue":"9","key":"pbio.3003559.ref064","first-page":"000670","article-title":"Different evolutionary trends form the twilight zone of the bacterial pan-genome","volume":"7","author":"G Horesh","year":"2021","journal-title":"Microb Genom"},{"key":"pbio.3003559.ref065","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.87406.3","article-title":"Bactabolize is a tool for high-throughput generation of bacterial strain-specific metabolic models","volume":"12","author":"B Vezina","year":"2023","journal-title":"Elife"},{"issue":"2","key":"pbio.3003559.ref066","first-page":"001206","article-title":"A validated pangenome-scale metabolic model for the Klebsiella pneumoniae species complex","volume":"10","author":"HB Cooper","year":"2024","journal-title":"Microb Genom"},{"issue":"3","key":"pbio.3003559.ref067","article-title":"Coinfinder: detecting significant associations and dissociations in pangenomes","volume":"6","author":"FJ Whelan","year":"2020","journal-title":"Microb Genom"},{"issue":"7","key":"pbio.3003559.ref068","doi-asserted-by":"crossref","first-page":"3783","DOI":"10.1128\/IAI.72.7.3783-3792.2004","article-title":"Isolation of a chromosomal region of Klebsiella pneumoniae associated with allantoin metabolism and liver infection","volume":"72","author":"H-C Chou","year":"2004","journal-title":"Infect Immun"},{"issue":"6912","key":"pbio.3003559.ref069","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/nature01149","article-title":"Escherichia coli K-12 undergoes adaptive evolution to achieve in silico predicted optimal growth","volume":"420","author":"RU Ibarra","year":"2002","journal-title":"Nature"},{"issue":"5","key":"pbio.3003559.ref070","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1111\/1462-2920.13689","article-title":"Metabolic diversity of the emerging pathogenic lineages of Klebsiella pneumoniae","volume":"19","author":"C Blin","year":"2017","journal-title":"Environ Microbiol"},{"issue":"1","key":"pbio.3003559.ref071","doi-asserted-by":"crossref","DOI":"10.1128\/msystems.00606-19","article-title":"MICOM: metagenome-scale modeling to infer metabolic interactions in the gut microbiota","volume":"5","author":"C Diener","year":"2020","journal-title":"mSystems"},{"issue":"22","key":"pbio.3003559.ref072","doi-asserted-by":"crossref","first-page":"8703","DOI":"10.1021\/ac2021823","article-title":"Toward global metabolomics analysis with hydrophilic interaction liquid chromatography-mass spectrometry: improved metabolite identification by retention time prediction","volume":"83","author":"DJ Creek","year":"2011","journal-title":"Anal Chem"},{"issue":"7","key":"pbio.3003559.ref073","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1093\/bioinformatics\/bts069","article-title":"IDEOM: an excel interface for analysis of LC-MS-based metabolomics data","volume":"28","author":"DJ Creek","year":"2012","journal-title":"Bioinformatics"},{"issue":"10","key":"pbio.3003559.ref074","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1038\/nbt.2377","article-title":"A cross-platform toolkit for mass spectrometry and proteomics","volume":"30","author":"MC Chambers","year":"2012","journal-title":"Nat Biotechnol"},{"key":"pbio.3003559.ref075","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1186\/1471-2105-9-504","article-title":"Highly sensitive feature detection for high resolution LC\/MS","volume":"9","author":"R Tautenhahn","year":"2008","journal-title":"BMC Bioinformatics"},{"issue":"7","key":"pbio.3003559.ref076","doi-asserted-by":"crossref","first-page":"2786","DOI":"10.1021\/ac2000994","article-title":"PeakML\/mzMatch: a file format, Java library, R library, and tool-chain for mass spectrometry data analysis","volume":"83","author":"RA Scheltema","year":"2011","journal-title":"Anal Chem"},{"key":"pbio.3003559.ref077","volume-title":"R: a language and environment for statistical computing","author":"R-Core-Team","year":"2020"},{"key":"pbio.3003559.ref078","volume-title":"RStudio: integrated development for R","author":"RStudio-Team","year":"2020"},{"issue":"43","key":"pbio.3003559.ref079","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.21105\/joss.01686","article-title":"Welcome to the Tidyverse","volume":"4","author":"H Wickham","year":"2019","journal-title":"JOSS"},{"key":"pbio.3003559.ref080","volume-title":"viridis: Default Color Maps from \u2018matplotlib\u2019","author":"S Garnier","year":"2018"},{"key":"pbio.3003559.ref081","volume-title":"RColorBrewer: ColorBrewer palettes","author":"E Neuwirth","year":"2014","edition":"1"},{"key":"pbio.3003559.ref082","volume-title":"ggpubr: \u2018ggplot2\u2019 based publication ready plots","author":"A Kassambara","year":"2022","edition":"0"},{"key":"pbio.3003559.ref083","volume-title":"ggpmisc: miscellaneous Extensions to \u2018ggplot2\u2019","author":"PJ Aphalo","year":"2021","edition":"0"},{"key":"pbio.3003559.ref084","volume-title":"aplot: Decorate a \u2018ggplot\u2019 with Associated Information","author":"G Yu","year":"2020","edition":"0"},{"issue":"1","key":"pbio.3003559.ref085","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v096.i01","article-title":"Colorspace: a toolbox for manipulating and assessing colors and palettes","volume":"96","author":"A Zeileis","year":"2020","journal-title":"J Stat Softw"},{"issue":"1","key":"pbio.3003559.ref086","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/2041-210X.12628","article-title":"ggtree: an R package for visualization and annotation of phylogenetic trees with their covariates and other associated data","volume":"8","author":"G Yu","year":"2016","journal-title":"Methods Ecol Evol"},{"key":"pbio.3003559.ref087","volume-title":"rstatix: pipe-friendly framework for basic statistical tests","author":"A Kassambara","year":"2023"},{"key":"pbio.3003559.ref088","volume-title":"ggnewscale: Multiple Fill and Colour Scales in \u2018ggplot2\u2019","author":"E Campitelli","year":"2021","edition":"0"},{"issue":"1","key":"pbio.3003559.ref089","doi-asserted-by":"crossref","DOI":"10.1093\/molbev\/msac232","article-title":"Prokaryotic pangenomes act as evolving ecosystems","volume":"40","author":"JO McInerney","year":"2023","journal-title":"Mol Biol Evol"},{"issue":"6","key":"pbio.3003559.ref090","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0253440","article-title":"Evaluating coverage bias in next-generation sequencing of Escherichia coli","volume":"16","author":"S Gunasekera","year":"2021","journal-title":"PLoS One"},{"issue":"1","key":"pbio.3003559.ref091","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s13073-022-01103-0","article-title":"ESBL plasmids in Klebsiella pneumoniae: diversity, transmission and contribution to infection burden in the hospital setting","volume":"14","author":"J Hawkey","year":"2022","journal-title":"Genome Med"},{"key":"pbio.3003559.ref092","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1007\/0-387-28022-7_13","volume-title":"Bergey\u2019s manual of systematic bacteriology","author":"J Imhoff","year":"2005"},{"issue":"1","key":"pbio.3003559.ref093","doi-asserted-by":"crossref","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":"M Rosenblueth","year":"2004","journal-title":"Syst Appl Microbiol"},{"key":"pbio.3003559.ref094","doi-asserted-by":"crossref","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":"S Brisse","year":"2014","journal-title":"Int J Syst Evol Microbiol"},{"issue":"3","key":"pbio.3003559.ref095","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.resmic.2019.02.003","article-title":"Description of Klebsiella africanensis sp. nov., Klebsiella variicola subsp. tropicalensis subsp. nov. and Klebsiella variicola subsp. variicola subsp. nov","volume":"170","author":"C Rodrigues","year":"2019","journal-title":"Res Microbiol"},{"issue":"4","key":"pbio.3003559.ref096","doi-asserted-by":"crossref","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":"KL Wyres","year":"2019","journal-title":"PLoS Genet"},{"key":"pbio.3003559.ref097","doi-asserted-by":"crossref","first-page":"9001","DOI":"10.1007\/s00253-019-10164-y","article-title":"Identification of major malate export systems in an engineered malate-producing Escherichia coli aided by substrate similarity search","volume":"103","author":"G Kurgan","year":"2019","journal-title":"Appl Microbiol Biotechnol"},{"issue":"8","key":"pbio.3003559.ref098","doi-asserted-by":"crossref","first-page":"160187","DOI":"10.1098\/rsos.160187","article-title":"Homeostasis of metabolites in Escherichia coli on transition from anaerobic to aerobic conditions and the transient secretion of pyruvate","volume":"3","author":"NA Yasid","year":"2016","journal-title":"R Soc Open Sci"},{"issue":"22","key":"pbio.3003559.ref099","doi-asserted-by":"crossref","first-page":"4455","DOI":"10.1039\/D1LC00676B","article-title":"Synthetic cellular communication-based screening for strains with improved 3-hydroxypropionic acid secretion","volume":"21","author":"S Kim","year":"2021","journal-title":"Lab Chip"},{"issue":"1","key":"pbio.3003559.ref100","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1128\/jb.113.1.51-57.1973","article-title":"Glutamate transport in Escherichia coli K-12: nonidentity of carriers mediating entry and exit","volume":"113","author":"YS Halpern","year":"1973","journal-title":"J Bacteriol"},{"issue":"11","key":"pbio.3003559.ref101","doi-asserted-by":"crossref","first-page":"2906","DOI":"10.1128\/JB.184.11.2906-2913.2002","article-title":"Plasmid-encoded asp operon confers a proton motive metabolic cycle catalyzed by an aspartate-alanine exchange reaction","volume":"184","author":"K Abe","year":"2002","journal-title":"J Bacteriol"},{"issue":"12","key":"pbio.3003559.ref102","doi-asserted-by":"crossref","first-page":"4027","DOI":"10.1128\/AEM.00003-11","article-title":"Inducible L-alanine exporter encoded by the novel gene ygaW (alaE) in Escherichia coli","volume":"77","author":"H Hori","year":"2011","journal-title":"Appl Environ Microbiol"},{"issue":"1","key":"pbio.3003559.ref103","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/s41396-022-01329-1","article-title":"Metabolic genes on conjugative plasmids are highly prevalent in Escherichia coli and can protect against antibiotic treatment","volume":"17","author":"A Palomino","year":"2023","journal-title":"ISME J"},{"issue":"5","key":"pbio.3003559.ref104","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1128\/IAI.01435-13","article-title":"Escherichia coli pathotypes occupy distinct niches in the mouse intestine","volume":"82","author":"JP Meador","year":"2014","journal-title":"Infect Immun"},{"issue":"5","key":"pbio.3003559.ref105","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1038\/s41396-020-00867-w","article-title":"Negative frequency-dependent selection and asymmetrical transformation stabilise multi-strain bacterial population structures","volume":"15","author":"GL Harrow","year":"2021","journal-title":"ISME J"},{"issue":"7","key":"pbio.3003559.ref106","doi-asserted-by":"crossref","DOI":"10.1002\/ece3.10327","article-title":"Negative frequency dependent selection unites ecology and evolution","volume":"13","author":"MR Christie","year":"2023","journal-title":"Ecol Evol"},{"issue":"11","key":"pbio.3003559.ref107","doi-asserted-by":"crossref","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":"JK Calland","year":"2023","journal-title":"Lancet Microbe"},{"issue":"12","key":"pbio.3003559.ref108","doi-asserted-by":"crossref","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":"HA Thorpe","year":"2022","journal-title":"Nat Microbiol"},{"issue":"1","key":"pbio.3003559.ref109","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s13073-025-01466-0","article-title":"A genome-wide One Health study of Klebsiella pneumoniae in Norway reveals overlapping populations but few recent transmission events across reservoirs","volume":"17","author":"MAK Hetland","year":"2025","journal-title":"Genome Med"},{"issue":"6676","key":"pbio.3003559.ref110","doi-asserted-by":"crossref","DOI":"10.1126\/science.adj3502","article-title":"Microbiome diversity protects against pathogens by nutrient blocking","volume":"382","author":"F Spragge","year":"2023","journal-title":"Science"},{"issue":"8031","key":"pbio.3003559.ref111","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1038\/s41586-024-07960-6","article-title":"Commensal consortia decolonize Enterobacteriaceae via ecological control","volume":"633","author":"M Furuichi","year":"2024","journal-title":"Nature"},{"issue":"11","key":"pbio.3003559.ref112","doi-asserted-by":"crossref","DOI":"10.1016\/j.chom.2021.09.003","article-title":"Klebsiella oxytoca causes colonization resistance against multidrug-resistant K. pneumoniae in the gut via cooperative carbohydrate competition","volume":"29","author":"L Osbelt","year":"2021","journal-title":"Cell Host Microbe"},{"issue":"11","key":"pbio.3003559.ref113","doi-asserted-by":"crossref","DOI":"10.1016\/j.chom.2021.09.004","article-title":"E. coli enhance colonization resistance against Salmonella Typhimurium by competing for galactitol, a context-dependent limiting carbon source","volume":"29","author":"C Eberl","year":"2021","journal-title":"Cell Host Microbe"},{"issue":"7","key":"pbio.3003559.ref114","article-title":"Differences in carbon metabolic capacity fuel co-existence and plasmid transfer between Salmonella strains in the mouse gut","volume":"31","author":"E G\u00fcl","year":"2023","journal-title":"Cell Host Microbe"}],"container-title":["PLOS Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3003559","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T18:31:27Z","timestamp":1765564287000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3003559"}},"subtitle":[],"editor":[{"given":"Sebastian E.","family":"Winter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,12,12]]},"references-count":114,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12,12]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pbio.3003559","relation":{},"ISSN":["1545-7885"],"issn-type":[{"value":"1545-7885","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,12]]}}}