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

Authors

Yanjun Liu, Zhiqian Wang, Zijuan Jian, Peilin Liu, Qun Yan, Wenen Liu

Published in

Microbiology spectrum. Pages e0068926. Aug 21, 2026. Epub Aug 21, 2026.

Abstract

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 bla_NDM-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.
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.

PMID:
42627181
Bibliographic data and abstract were imported from PubMed on 21 Aug 2026.

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