{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T09:50:22Z","timestamp":1782899422140,"version":"3.54.5"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To characterize a carbapenem-resistant\n                      <jats:italic>Citrobacter freundii<\/jats:italic>\n                      (CR-CFR) clinical isolate belonging to the sequence type ST116 and to investigate the public-genome distribution of ST116 among carbapenem-resistant\n                      <jats:italic>C. freundii<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A carbapenem-resistant\n                      <jats:italic>C. freundii<\/jats:italic>\n                      isolate (WF1033) was recovered from a patient with a urinary tract infection. Antimicrobial susceptibility testing, whole-genome sequencing, and detailed plasmid structural analyses were performed. To contextualize this isolate, a large-scale genomic analysis of publicly available CR-CFR genomes was conducted, including multilocus sequence typing (MLST), minimum spanning tree analysis, global distribution mapping, and phylogenetic reconstruction of sequence type ST116.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      WF1033 exhibited an extensively drug-resistant phenotype and harbored three carbapenemase genes,\n                      <jats:italic>bla<\/jats:italic>\n                      <jats:sub>KPC-2<\/jats:sub>\n                      ,\n                      <jats:italic>bla<\/jats:italic>\n                      <jats:sub>IMP-8<\/jats:sub>\n                      , and\n                      <jats:italic>bla<\/jats:italic>\n                      <jats:sub>NDM-1<\/jats:sub>\n                      . Genomic analysis revealed that WF1033 belongs to ST116 and carries four plasmids. Notably,\n                      <jats:italic>bla<\/jats:italic>\n                      <jats:sub>KPC-2<\/jats:sub>\n                      and\n                      <jats:italic>bla<\/jats:italic>\n                      <jats:sub>IMP-8<\/jats:sub>\n                      were co-located on a novel hybrid IncFIB\/IncFII plasmid (pWF1033-KPC-IMP), formed through the integration of distinct mobile genetic elements, whereas\n                      <jats:italic>bla<\/jats:italic>\n                      <jats:sub>NDM-1<\/jats:sub>\n                      was carried on a typical IncX3 plasmid. Analysis of 2,436 CR-CFR genomes identified 171 sequence types, with ST22 being the most prevalent globally. However, ST116 showed marked regional enrichment in China, accounting for 56.97% of all ST116 isolates. ST116 also displayed a higher proportion of strains carrying multiple carbapenem resistance genes (CRGs) compared with other major sequence types. Phylogenetic analysis of 165 ST116 isolates revealed multiple clades, suggesting possible lineage expansion and geographic persistence within this sequence type, with WF1033 representing the only ST116 strain identified to date carrying three CRGs simultaneously.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our findings suggest that ST116 represents a lineage associated with increased carriage of multiple carbapenem resistance genes in CR-CFR. Continuous genomic surveillance is warranted to monitor the dissemination of multidrug-resistant\n                      <jats:italic>C. freundii<\/jats:italic>\n                      , particularly among ST116-associated lineages.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1846731","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T09:28:24Z","timestamp":1782898104000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Distribution of ST116 carbapenem-resistant Citrobacter freundii in public genomes and characterization of a triple-carbapenemase-producing strain"],"prefix":"10.3389","volume":"16","author":[{"given":"Wanxiang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, Weifang People\u2019s Hospital, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Weifang People\u2019s Hospital, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Weifang People\u2019s Hospital, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Weifang People\u2019s Hospital, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Weifang People\u2019s Hospital, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1016\/j.jgar.2024.01.006","article-title":"Genomic scan of a healthcare-associated NDM-1-producing Citrobacter freundii ST18 isolated from a green sea turtle impacted by plastic pollution","volume":"36","author":"Aravena-Ram\u00edrez","year":"2024","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1128\/msphere.00366-23","article-title":"Nationwide molecular epidemiology of carbapenemase-producing Citrobacter spp. in France in 2019 and 2020","volume":"8","author":"Biez","year":"2023","journal-title":"mSphere"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1093\/jac\/dkac005","article-title":"Characterization of VIM-1-, NDM-1- and OXA-48-producing citrobacter freundii in France","volume":"77","author":"Biez","year":"2022","journal-title":"J. Antimicrob. Chemother."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi1003s00","article-title":"Using MUMmer to identify similar regions in large sequence sets","author":"Delcher","year":"2003","journal-title":"Curr. Protoc. Bioinf."},{"key":"B5","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.jgar.2024.02.015","article-title":"Coexistence of blaNDM-5, blaCTX-M-15, blaOXA-232, blaSHV-182 genes in multidrug-resistant K. pneumoniae ST437-carrying OmpK36 and OmpK37 porin mutations: First report in Italy","volume":"37","author":"Di Marcantonio","year":"2024","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.12669\/pjms.39.5.7188","article-title":"Co-existence of blaIMP, blaNDM-1, and blaSHV, genes of Pseudomonas aeruginosa isolated from Quetta: Antimicrobial resistance and clinical significance","volume":"39","author":"Din","year":"2023","journal-title":"Pak. J. Med. Sci."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.1048516","article-title":"Outbreak of carbapenem-resistant enterobacteria in a thoracic-oncology unit through clonal and plasmid-mediated transmission of the blaOXA-48 gene in Southern France","volume":"12","author":"Hadjadj","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s13756-023-01261-9","article-title":"Sanitary installations and wastewater plumbing as reservoir for the long-term circulation and transmission of carbapenemase producing Citrobacter freundii clones in a hospital setting","volume":"12","author":"Hamerlinck","year":"2023","journal-title":"Antimicrob. Resist. Infect. Ctrl"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.2147\/IDR.S347943","article-title":"Co-production of NDM-1 and OXA-10 \u03b2-lactamase in Citrobacter braakii strain causing urinary tract infection","volume":"15","author":"Han","year":"2022","journal-title":"Infect. Drug Resist."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2025.107463","article-title":"Emergence of carbapenem-resistant Citrobacter spp. across human, animal, and water environments in China","volume":"65","author":"Ju","year":"2025","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1093\/molbev\/msy096","article-title":"MEGA X: Molecular evolutionary genetics analysis across computing platforms","volume":"35","author":"Kumar","year":"2018","journal-title":"Mol. Biol. Evol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"W256","DOI":"10.1093\/nar\/gkz239","article-title":"Interactive Tree Of Life (iTOL) v4: Recent updates and new developments","volume":"47","author":"Letunic","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.jgar.2022.04.014","article-title":"Genomic characterization of a carbapenem-resistant Citrobacter freundii cocarrying blaKPC-2 and blaNDM-1","volume":"29","author":"Li","year":"2022","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"B14","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1093\/bioinformatics\/btw582","article-title":"PHYLOViZ 2.0: Providing scalable data integration and visualization for multiple phylogenetic inference methods","volume":"33","author":"Nascimento","year":"2017","journal-title":"Bioinformatics"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.04144-22","article-title":"Molecular epidemiology of global carbapenemase-producing Citrobacter spp. (2015-2017)","volume":"11","author":"Nobrega","year":"2023","journal-title":"Microbiol. Spectr"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.es.2024.29.11.2300521","article-title":"Regional dissemination of NDM-1 producing Enterobacter hormaechei ST1740, with a subset of strains co-producing VIM-4 or IMP-13, France, 2019 to 2022","volume":"29","author":"Rezzoug","year":"2024","journal-title":"Euro Surveill"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1352851","article-title":"First report of coexistence of blaKPC-2 and blaNDM-1 in carbapenem-resistant clinical isolates of Klebsiella aerogenes in Brazil","volume":"15","author":"Rodrigues","year":"2024","journal-title":"Front. Microbiol."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241512515","article-title":"Co-existence of blaNDM-1, blaOXA-23, blaOXA-64, blaPER-7 and blaADC-57 in a clinical isolate of Acinetobacter baumannii from Alexandria, Egypt","volume":"24","author":"S\u00e1nchez-Urtaza","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.50671","article-title":"Coexistence of blaNDM and blaOXA-48 genes in carbapenem-resistant Burkholderia pseudomallei isolated from pus: A rare phenomenon","volume":"15","author":"Verma","year":"2023","journal-title":"Cureus"},{"key":"B20","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1002\/mlf2.12046","article-title":"DANMEL: A manually curated reference database for analyzing mobile genetic elements associated with bacterial drug resistance","volume":"1","author":"Wang","year":"2022","journal-title":"mLife"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02282-18","article-title":"Cocarriage of distinct blaKPC-2 and blaOXA-48 plasmids in a single sequence type 11 carbapenem-resistant Klebsiella pneumoniae isolate","volume":"63","author":"Wang","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"B22","doi-asserted-by":"publisher","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":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/srep30670","article-title":"Citrobacter freundii carrying blaKPC-2 and blaNDM-1: Characterization by whole genome sequencing","volume":"6","author":"Wu","year":"2016","journal-title":"Sci. Rep."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/adbi.201900219","article-title":"Carriage of distinct blaKPC-2 and blaOXA-48 plasmids in a single ST11 hypervirulent Klebsiella pneumoniae isolate in Egypt","volume":"23","author":"Yang","year":"2022","journal-title":"BMC Genomics"},{"key":"B25","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1186\/s12864-023-09579-9","article-title":"Complete-genome sequencing and comparative genomic characterization of blaNDM-5 carrying Citrobacter freundii isolates from a patient with multiple infections","volume":"24","author":"Ye","year":"2023","journal-title":"BMC Genomics"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1153366","DOI":"10.1016\/j.meegid.2025.105740","article-title":"First report of coexistence of blaKPC-2-, blaNDM-1- and mcr-9-carrying plasmids in a clinical carbapenem-resistant Enterobacter hormaechei isolate","volume":"14","author":"Yuan","year":"2023","journal-title":"Front. Microbiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1239538","DOI":"10.1016\/j.drup.2026.101422","article-title":"Carbapenem-resistant Citrobacter freundii harboring blaKPC-2 and blaNDM-1: A study on their transferability and potential dissemination via generating a transferrable hybrid plasmid mediated by IS6100","volume":"14","author":"Zhang","year":"2023","journal-title":"Front. Microbiol."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01354-22","article-title":"Molecular characteristics of an NDM-4 and OXA-181 co-producing K51-ST16 carbapenem-resistant Klebsiella pneumoniae: Study of its potential dissemination mediated by conjugative plasmids and insertion sequences","volume":"67","author":"Zhang","year":"2023","journal-title":"Antimicrob. Agents Chemother."},{"key":"B29","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.jgar.2025.03.003","article-title":"Epidemiology, phylogeny and genetic characterization of carbapenem-resistant Citrobacter spp. from 5 hospitals in China","volume":"42","author":"Zhao","year":"2025","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1128\/msphere.00612-23","article-title":"Emergence of KPC-2 and NDM-5-coproducing hypervirulent carbapenem-resistant Klebsiella pneumoniae with high-risk sequence types ST11 and ST15","volume":"9","author":"Zhou","year":"2024","journal-title":"mSphere"},{"key":"B31","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/s10096-022-04512-6","article-title":"Coexistence of tet(A) and blaKPC-2 in the ST11 hypervirulent tigecycline- and carbapenem-resistant Klebsiella pneumoniae isolated from a blood sample","volume":"42","author":"Zhu","year":"2023","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1846731\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T09:28:24Z","timestamp":1782898104000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1846731\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":31,"alternative-id":["10.3389\/fcimb.2026.1846731"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2026.1846731","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,1]]},"article-number":"1846731"}}