Academic Journal

Characterization of tmexCD-toprJ-harboring plasmid in Klebsiella pneumoniae: insights into the molecular epidemiology of tigecycline resistance.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Characterization of tmexCD-toprJ-harboring plasmid in Klebsiella pneumoniae: insights into the molecular epidemiology of tigecycline resistance.
Συγγραφείς: Liu Y; Department of Clinical Laboratory, The Central Hospital of Yongzhou, Yongzhou Clinical College, University of South China, Yongzhou, Hunan, China.; Department of Clinical Laboratory, Xiangya Hospital,Central South University, Changsha, Hunan, China., Wang Z; Department of Clinical Laboratory, Xiangya Hospital,Central South University, Changsha, Hunan, China.; Department of Clinical Laboratory, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China., Jian Z; Department of Clinical Laboratory, Xiangya Hospital,Central South University, Changsha, Hunan, China., Liu P; Department of Clinical Laboratory, Xiangya Hospital,Central South University, Changsha, Hunan, China., Yan Q; Department of Clinical Laboratory, Xiangya Hospital,Central South University, Changsha, Hunan, China., Liu W; Department of Clinical Laboratory, Xiangya Hospital,Central South University, Changsha, Hunan, China.; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China.
Πηγή: Microbiology spectrum [Microbiol Spectr] 2026 Oct 06; Vol. 14 (10), pp. e0068926. Date of Electronic Publication: 2026 Aug 21.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: ASM Press Country of Publication: United States NLM ID: 101634614 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2165-0497 (Electronic) Linking ISSN: 21650497 NLM ISO Abbreviation: Microbiol Spectr Subsets: MEDLINE
Imprint Name(s): Original Publication: Washington, DC : ASM Press, 2013-
Ιατρικοί όροι (MeSH): Tigecycline*/pharmacology , Klebsiella pneumoniae*/genetics , Klebsiella pneumoniae*/drug effects , Klebsiella pneumoniae*/isolation & purification , Plasmids*/genetics , Plasmids*/metabolism , Anti-Bacterial Agents*/pharmacology , Klebsiella Infections*/microbiology , Klebsiella Infections*/epidemiology , Drug Resistance, Multiple, Bacterial*/genetics, Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Drug Resistance, Bacterial/genetics ; Microbial Sensitivity Tests ; Humans ; Molecular Epidemiology ; Whole Genome Sequencing ; Multigene Family
Περίληψη: Tigecycline-non-susceptible Klebsiella pneumoniae (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 tmexCD-toprJ remain incompletely understood. Our study aims to investigate the epidemiological characteristics and genetic traits of tmexCD-toprJ 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 tmexCD-toprJ. We identified 25 TNSKP strains, including 17 carbapenem-resistant Klebsiella pneumoniae (CRKP) and 8 non-CRKP strains. The tigecycline MIC values were 4 µg/mL (14 strains), 8 µg/mL (nine strains), and 16 µg/mL (two strains). Multiple resistance mechanisms were detected, including AcrR, RamR, tet(A) mutations, and tmexCD-toprJ. The tmexCD-toprJ gene cluster was found in three strains: ST334 CRKP and ST39 CRKP (both carrying tmexCD2-toprJ2) and ST656 CRKP (carrying tmexCD1-toprJ1). ST39 CRKP also harbored blaNDM-1, tmexCD2-toprJ2, and iuc3 on IncFIB(K), IncU, and IncFII(K) plasmids, with a complete conjugation element. Our research identified multiple complex tigecycline resistance mechanisms in K. pneumoniae, including new ST types carrying tmexCD2-toprJ2. 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.
Importance: Tigecycline-non-susceptible Klebsiella pneumoniae (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.
Competing Interests: The authors declare no conflict of interest.
References: Lancet Microbe. 2023 Mar;4(3):e134. (PMID: 36436539)
Microbiol Spectr. 2024 Oct 3;12(10):e0387423. (PMID: 39162556)
J Clin Microbiol. 2022 Mar 16;60(3):e0027621. (PMID: 34346716)
J Antimicrob Chemother. 2020 Dec 1;75(12):3491-3500. (PMID: 32780112)
Antimicrob Agents Chemother. 2014 Jul;58(7):3895-903. (PMID: 24777092)
Nat Microbiol. 2024 Mar;9(3):814-829. (PMID: 38424289)
Lancet Microbe. 2022 Nov;3(11):e846-e856. (PMID: 36202114)
Sci Total Environ. 2024 Jan 1;906:167373. (PMID: 37758131)
Int J Mol Sci. 2024 Feb 02;25(3):. (PMID: 38339095)
Front Cell Infect Microbiol. 2025 Mar 13;15:1540967. (PMID: 40182765)
Sci Total Environ. 2024 Nov 25;953:176065. (PMID: 39244063)
Nucleic Acids Res. 2014 Jan;42(Database issue):D206-14. (PMID: 24293654)
Eur J Clin Microbiol Infect Dis. 2022 Jul;41(7):1003-1022. (PMID: 33403565)
mSphere. 2021 Aug 25;6(4):e0059221. (PMID: 34346701)
Lancet Microbe. 2024 Feb;5(2):e105. (PMID: 37972633)
Nucleic Acids Res. 2023 Jul 5;51(W1):W484-W492. (PMID: 37140037)
Nat Commun. 2023 Dec 2;14(1):7962. (PMID: 38042959)
Gigascience. 2024 Jan 2;13:. (PMID: 39101782)
Microbiol Spectr. 2023 Apr 13;11(2):e0278622. (PMID: 36719204)
Lancet Infect Dis. 2022 Mar;22(3):401-412. (PMID: 34767753)
Drug Resist Updat. 2023 Sep;70:100989. (PMID: 37480594)
EBioMedicine. 2022 May;79:103998. (PMID: 35405387)
IEEE/ACM Trans Comput Biol Bioinform. 2022 Nov-Dec;19(6):3564-3577. (PMID: 34469305)
mSystems. 2020 Apr 28;5(2):. (PMID: 32345737)
Clin Microbiol Rev. 2019 May 15;32(3):. (PMID: 31092506)
Microbiol Mol Biol Rev. 2025 Dec 18;89(4):e0027824. (PMID: 41263575)
Int J Antimicrob Agents. 2021 Feb;57(2):106251. (PMID: 33259915)
Microbiol Spectr. 2021 Dec 22;9(3):e0116421. (PMID: 34935428)
J Antimicrob Chemother. 2022 Jun 29;77(7):2030-2033. (PMID: 35451006)
Int J Antimicrob Agents. 2025 Nov;66(5):107566. (PMID: 40617549)
J Clin Microbiol. 2018 Aug 27;56(9):. (PMID: 29925642)
Emerg Microbes Infect. 2024 Dec;13(1):2306957. (PMID: 38240375)
Int J Antimicrob Agents. 2024 Feb;63(2):107055. (PMID: 38081547)
Infect Drug Resist. 2024 Nov 21;17:5117-5128. (PMID: 39600323)
Int J Food Microbiol. 2026 Jan 30;446:111540. (PMID: 41308489)
Emerg Microbes Infect. 2022 Dec;11(1):1936-1949. (PMID: 35844192)
Grant Information: 2025JJ70503 Hunan Provincial Natural Science Foundation Regional Joint Fund Project
Contributed Indexing: Keywords: carbapenem-resistant Klebsiella pneumoniae; resistance mechanisms; tigecycline; tmexCD-toprJ
Substance Nomenclature: 70JE2N95KR (Tigecycline)
0 (Anti-Bacterial Agents)
0 (Bacterial Proteins)
Entry Date(s): Date Created: 20260821 Date Completed: 20261007 Latest Revision: 20261024
Update Code: 20261024
PubMed Central ID: PMC13688829
DOI: 10.1128/spectrum.00689-26
PMID: 42627181
Βάση Δεδομένων: MEDLINE