Emergence of high-level tigecycline resistance due to the amplification of a tet(A) gene variant in clinical carbapenem-resistant Klebsiella pneumoniae

Runhao Yu; Longyu Li; Chenhui Zou; Zheng Chen; Stefan Schwarz; Sheng Chen; Chunyan Xu; Hong Yao; Xiang-Dang Du

doi:10.1016/j.cmi.2023.07.030

Emergence of high-level tigecycline resistance due to the amplification of a tet(A) gene variant in clinical carbapenem-resistant Klebsiella pneumoniae

Clin Microbiol Infect. 2023 Aug 5:S1198-743X(23)00358-0. doi: 10.1016/j.cmi.2023.07.030. Online ahead of print.

Authors

Runhao Yu¹, Longyu Li¹, Chenhui Zou¹, Zheng Chen¹, Stefan Schwarz², Sheng Chen³, Chunyan Xu¹, Hong Yao¹, Xiang-Dang Du⁴

Affiliations

¹ College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, People's Republic of China.
² Institute of Microbiology and Epizootics, Centre for Infection Medicine, School of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany; Veterinary Centre of Resistance Research (TZR), Freie Universität Berlin, Berlin, Germany.
³ Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong.
⁴ College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, People's Republic of China. Electronic address: xddu@henau.edu.cn.

PMID: 37549732
DOI: 10.1016/j.cmi.2023.07.030

Abstract

Objective: To investigate the prevalence of a tet(A) gene variant and its role in developing high-level tigecycline resistance among carbapenem-resistant Klebsiella pneumoniae (CRKP) clinical isolates.

Methods: The mechanism of high-level tigecycline resistance in CRKP mediated by a tet(A) variant was explored by induction experiments, antimicrobial susceptibility testing, whole-genome sequencing and bioinformatics analysis. The amplification and overexpression of the tet(A) variant were measured by the determination of sequencing depth, gene copy numbers, and qRT-PCR.

Results: A high rate (62.1%, 998/1607) of tet(A) variant carriage was observed among 1607 CRKP clinical isolates from Henan Province, China. High-level tigecycline resistance could rapidly develop by the amplification of the tet(A) variant in these isolates. The analysis of the raw sequencing data and the plasmid mapping depth revealed that the ΔtnpA homologous sequence of Tn1721 supports the amplification of the region that harbours the tet(A) variant by forming a large number of repeat arrays through translocatable units (TUs). Moreover, the epidemiological analysis of tet(A) variant-carrying structures among 1607 clinical CRKPs showed that the TU structure is widely present.

Conclusion: The presence of a tigecycline resistance-mediating tet(A) variant in CRKP clinical isolates represents a greater health concern than initially thought and should be monitored consistently.

Keywords: Amplification; Carbapenem-resistant Klebsiella pneumoniae; Tigecycline resistance; Translocatable units; tet(A) variant.