{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T10:25:06Z","timestamp":1782987906087,"version":"3.54.5"},"reference-count":27,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:00:00Z","timestamp":1738627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:00:00Z","timestamp":1738627200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Medical Science and Technology Project of Henan Province","award":["LHG20240580"],"award-info":[{"award-number":["LHG20240580"]}]},{"name":"Key Research, Development Promotion Projects fo Henan Province","award":["222102310328"],"award-info":[{"award-number":["222102310328"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,2,4]]},"abstract":"ABSTRACT<\/jats:title>\n \n \n \n The rise of carbapenem-resistant\n Enterobacteriaceae<\/jats:italic>\n coharboring KPC-2 and NDM-1 poses a significant public health threat. KPC-2-NDM-1-\n Citrobacter freundii<\/jats:italic>\n is rarely reported in clinical settings. In this study, we report the largest cohort of eight KPC-2-NDM-1-\n C. freundii<\/jats:italic>\n isolated from children with urinary tract infections. Comprehensive characterization, including antimicrobial susceptibility testing, plasmid conjugation, whole-genome sequencing, and comparative genomics, was conducted for these clinical strains. Antimicrobial susceptibility testing indicated that all strains were resistant to meropenem [minimal inhibitory concentration (MICs) \u2265 8 \u00b5g\/mL] and imipenem (MICs > 8 \u00b5g\/mL). Genotyping and comparative genomics analyses identified the eight KPC-2-NDM-1-\n C. freundii<\/jats:italic>\n belonging to ST523, exhibiting a close relationship characterized by 45 single nucleotide polymorphisms. Whole-genome sequencing and plasmid analysis confirmed the presence of\n bla<\/jats:italic>\n KPC-2<\/jats:sub>\n and\n bla<\/jats:italic>\n NDM-1<\/jats:sub>\n on an IncR plasmid named pC275-2 with 46,050 bp. The\n bla<\/jats:italic>\n NDM-1<\/jats:sub>\n was integrated within the\n bla<\/jats:italic>\n NDM-1<\/jats:sub>\n related region, which includes \u0394IS\n Aba125<\/jats:italic>\n ,\n bla<\/jats:italic>\n NDM-1<\/jats:sub>\n ,\n ble-MBL<\/jats:italic>\n ,\n trpF<\/jats:italic>\n ,\n dsbD<\/jats:italic>\n , and IS\n CR1<\/jats:italic>\n , while the\n bla<\/jats:italic>\n KPC-2<\/jats:sub>\n gene was located on a novel non-Tn\n 4401<\/jats:italic>\n genetic element. The\n bla<\/jats:italic>\n KPC-2<\/jats:sub>\n genetic architectures containing\n bla<\/jats:italic>\n KPC-2<\/jats:sub>\n differed from classical structures, underscoring the ongoing evolution of these genetic elements.\n <\/jats:p>\n \n IMPORTANCE<\/jats:title>\n \n Our study described the largest cohort to date of eight ST523 KPC-2-NDM-1-\n C. freundii<\/jats:italic>\n isolated from children with urinary tract infections. The cooccurrence of KPC-2, a serine\n \u03b2<\/jats:italic>\n -lactamases, and NDM-1, a metallo-\u03b2-lactamase on an IncR plasmid pC275-2 from a clinical carbapenem-resistant\n C<\/jats:italic>\n .\n freundii<\/jats:italic>\n . The conserved insertion structure mediated the\n bla<\/jats:italic>\n NDM-1<\/jats:sub>\n , and the propagation of\n bla<\/jats:italic>\n KPC-2<\/jats:sub>\n gene with a new genetic background using IncR plasmid in clinical settings promotes the emergence of superbugs necessitating vigilant monitoring. Our research detected that ST523 KPC-2- NDM-1-\n C. freundii<\/jats:italic>\n were disseminated in a children\u2019s hospital. The potential spread of an IncR plasmid within the hospital raises concerns about the pandemic potential of this clone that produces two carbapenemases: KPC-2 and NDM-1. Further investigations will be necessary to control and prevent the spread of KPC-2-NDM-1-\n C. freundii<\/jats:italic>\n s.\n <\/jats:p>\n <\/jats:sec>\n <\/jats:sec>","DOI":"10.1128\/spectrum.01953-24","type":"journal-article","created":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T14:28:01Z","timestamp":1734618481000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["Emergence and clonal dissemination of KPC-2- and NDM-1-coharboring\n Citrobacter freundii<\/i>\n in China with an IncR plasmid"],"prefix":"10.1128","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4066-455X","authenticated-orcid":true,"given":"Juanjuan","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, Children\u2019s Hospital Affiliated to Zhengzhou University, Henan Children\u2019s Hospital, Zhengzhou Children\u2019s Hospital, Zhengzhou Key Laboratory of Children\u2019s Infection and Immunity","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghui","family":"Zhen","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Children\u2019s Hospital Affiliated to Zhengzhou University, Henan Children\u2019s Hospital, Zhengzhou Children\u2019s Hospital, Zhengzhou Key Laboratory of Children\u2019s Infection and Immunity","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaijie","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Children\u2019s Hospital Affiliated to Zhengzhou University, Henan Children\u2019s Hospital, Zhengzhou Children\u2019s Hospital, Zhengzhou Key Laboratory of Children\u2019s Infection and Immunity","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Children\u2019s Hospital Affiliated to Zhengzhou University, Henan Children\u2019s Hospital, Zhengzhou Children\u2019s Hospital, Zhengzhou Key Laboratory of Children\u2019s Infection and Immunity","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Children\u2019s Hospital Affiliated to Zhengzhou University, Henan Children\u2019s Hospital, Zhengzhou Children\u2019s Hospital, Zhengzhou Key Laboratory of Children\u2019s Infection and Immunity","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junmei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Children\u2019s Hospital Affiliated to Zhengzhou University, Henan Children\u2019s Hospital, Zhengzhou Children\u2019s Hospital, Zhengzhou Key Laboratory of Children\u2019s Infection and Immunity","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmii.2016.08.016"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-008-0598-z"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-28879-9"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00275-20"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2018.00233"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S165818"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2013.02.007"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02609-18"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.102599"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmni.2022.101051"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1089\/mdr.2014.0171"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2022.119437"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgar.2022.04.014"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S426148"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2014.09.003"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00464-16"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/cmr.00008-23"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S256922"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1074612"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1239538"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00260-09"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.622280B2"},{"key":"e_1_3_4_24_2","volume-title":"Clinical 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