{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:56:16Z","timestamp":1791294976003,"version":"4.1.0"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Hunan Provincial Natural Science Foundation Regional Joint Fund Project","award":["2025JJ70503"],"award-info":[{"award-number":["2025JJ70503"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,10,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Tigecycline-non-susceptible\n                      <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                      (TNSKP) is a significant global public health threat. The molecular epidemiological characteristics of the novel resistance mechanisms mediated by the mobile resistance-nodulation-cell division-type efflux pump gene cluster\n                      <jats:italic toggle=\"yes\">tmexCD-toprJ<\/jats:italic>\n                      remain incompletely understood. Our study aims to investigate the epidemiological characteristics and genetic traits of\n                      <jats:italic toggle=\"yes\">tmexCD-toprJ<\/jats:italic>\n                      in TNSKP. We collected 980 KP isolates from a tertiary teaching hospital between 2020 and 2021, screening for TNSKP strains by microbroth dilution. Whole-genome sequencing was used to analyze the molecular epidemiological characteristics and resistance mechanisms of TNSKP and to resolve the genetic structure of the plasmid carrying\n                      <jats:italic toggle=\"yes\">tmexCD-toprJ<\/jats:italic>\n                      . We identified 25 TNSKP strains, including 17 carbapenem-resistant\n                      <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                      (CRKP) and 8 non-CRKP strains. The tigecycline MIC values were 4 \u00b5g\/mL (14 strains), 8 \u00b5g\/mL (nine strains), and 16 \u00b5g\/mL (two strains). Multiple resistance mechanisms were detected, including\n                      <jats:italic toggle=\"yes\">AcrR<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">RamR<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">tet<\/jats:italic>\n                      (A) mutations, and\n                      <jats:italic toggle=\"yes\">tmexCD-toprJ<\/jats:italic>\n                      . The\n                      <jats:italic toggle=\"yes\">tmexCD-toprJ<\/jats:italic>\n                      gene cluster was found in three strains: ST334 CRKP and ST39 CRKP (both carrying\n                      <jats:italic toggle=\"yes\">tmexCD2-toprJ2<\/jats:italic>\n                      ) and ST656 CRKP (carrying\n                      <jats:italic toggle=\"yes\">tmexCD1-toprJ1<\/jats:italic>\n                      ). ST39 CRKP also harbored\n                      <jats:italic toggle=\"yes\">bla<\/jats:italic>\n                      <jats:sub>NDM-1<\/jats:sub>\n                      ,\n                      <jats:italic toggle=\"yes\">tmexCD2-toprJ2<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">iuc3<\/jats:italic>\n                      on IncFIB(K), IncU, and IncFII(K) plasmids, with a complete conjugation element. Our research identified multiple complex tigecycline resistance mechanisms in\n                      <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                      , including new ST types carrying\n                      <jats:italic toggle=\"yes\">tmexCD2-toprJ2<\/jats:italic>\n                      . A fusion plasmid harboring virulence genes, carbapenem resistance genes, and tigecycline resistance genes was discovered. Continuous molecular epidemiological monitoring plays a crucial role in elucidating the mechanisms of tigecycline resistance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Tigecycline-non-susceptible\n                      <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                      (TNSKP) poses a significant global public health threat. The molecular epidemiological characteristics of the novel resistance mechanisms mediated by the mobile resistance-nodulation-cell division-type efflux pump gene cluster tmexCD-toprJ remain incompletely understood. Our study aims to investigate the epidemiological characteristics and genetic traits of tmexCD-toprJ cluster in TNSKP. This study has revealed the coexistence of multiple mechanisms contributing to tigecycline resistance. In clinical settings, we have identified various types of the tmexCD-toprJ gene cluster, among which two ST types (ST334 and ST39) carrying the tmexCD2-toprJ2 gene cluster are reported for the first time. Additionally, a fusion plasmid containing both the tmexCD2-toprJ2 gene cluster and carbapenemase resistance gene blaNDM-1 as well as virulence gene iuc3 has been detected. These findings highlight that molecular epidemiological monitoring provides important evidence for bacterial resistance and evolution. Continuous monitoring and controlling the spread of resistance from a One Health perspective are meaningful.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.00689-26","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:03:39Z","timestamp":1787317419000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Characterization of\n                    <i>tmexCD-toprJ<\/i>\n                    -harboring plasmid in\n                    <i>Klebsiella pneumoniae<\/i>\n                    : insights into the molecular epidemiology of tigecycline resistance"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7673-6370","authenticated-orcid":true,"given":"Yanjun","family":"Liu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03mqfn238","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Laboratory, The Central Hospital of Yongzhou, Yongzhou Clinical College, University of South China","place":["Yongzhou, China"]},{"id":[{"id":"https:\/\/ror.org\/05c1yfj14","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Laboratory, Xiangya Hospital,Central South University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqian","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05c1yfj14","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Laboratory, Xiangya Hospital,Central South University","place":["Changsha, China"]},{"id":[{"id":"https:\/\/ror.org\/026axqv54","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Laboratory, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijuan","family":"Jian","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05c1yfj14","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Laboratory, Xiangya Hospital,Central South University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peilin","family":"Liu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05c1yfj14","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Laboratory, Xiangya Hospital,Central South University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Yan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05c1yfj14","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Laboratory, Xiangya Hospital,Central South University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2561-1118","authenticated-orcid":false,"given":"Wenen","family":"Liu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05c1yfj14","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Laboratory, Xiangya Hospital,Central South University","place":["Changsha, China"]},{"name":"National Clinical Research Center for Geriatric Disorders, Xiangya Hospital","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.103998"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(21)00399-6"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-024-01612-1"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-020-04121-1"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2020.106251"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSystems.00134-20"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/Spectrum.01164-21"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/mmbr.00278-24"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2024.176065"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2023.100989"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkac136"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-5247(22)00221-X"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2023.167373"},{"key":"e_1_3_5_15_2","volume-title":"Performance standards for antimicrobial susceptibility testing","author":"Clinical and Laboratory Standards Institute","year":"2023","unstructured":"Clinical and Laboratory Standards Institute. 2023. 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