Publikationsdatenbank

Emergence of high-level tigecycline resistance due to the amplification of a tet(A) gene variant in clinical carbapenem-resistant Klebsiella pneumoniae (2023)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Yu, Runhao

Li, Longyu

Zou, Chenhui

Chen, Zheng

Schwarz, Stefan (WE 7)

Chen, Sheng

Xu, Chunyan

Yao, Hong

Du, Xiang-Dang

Quelle

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases ; CMI

Bandzählung: 29

Heftzählung: 11

Seiten: 1452.e1 – 1452.e7

ISSN: 1470-9465

Sprache

Englisch

Verweise

URL (Volltext): https://pubmed.ncbi.nlm.nih.gov/37549732/

DOI: 10.1016/j.cmi.2023.07.030

Pubmed: 37549732

Kontakt

Institut für Mikrobiologie und Tierseuchen

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51843 / 66949
mikrobiologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.