Emergence of tet(X2) in Acinetobacter pittii confers clinical resistance to tigecycline

Abstract Objectives To characterize a novel transposon Tn7533 carrying the tet(X2) gene in a tigecycline-resistant Acinetobacter pittii BM4623 of clinical origin. Methods Gene knockout and in vitro cloning were used to verify the function of tet(X2). WGS and comparative genomic analysis were used to...

Full description

Saved in:
Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 2023-06, Vol.78 (6), p.1543-1546
Main Authors: Qian, Changrui, Ma, Zhexiao, Feng, Luozhu, Guo, Wenhui, Han, Yijia, Zhang, Yi, Xu, Chunquan, Cao, Jianming, Zhou, Tieli
Format: Article
Language:English
Subjects:
Acinetobacter - genetics
Acinetobacter baumannii - genetics
Acinetobacter Infections - drug therapy
Anti-Bacterial Agents - pharmacology
Anti-Bacterial Agents - therapeutic use
Humans
Microbial Sensitivity Tests
Plasmids
Tigecycline - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Objectives To characterize a novel transposon Tn7533 carrying the tet(X2) gene in a tigecycline-resistant Acinetobacter pittii BM4623 of clinical origin. Methods Gene knockout and in vitro cloning were used to verify the function of tet(X2). WGS and comparative genomic analysis were used to explore the genetic characteristics and molecular evolution of tet(X2). Inverse PCR and electroporation experiments were used to evaluate the excision and integration capabilities of Tn7533. Results A. pittii BM4623 belonged to a novel ST, ST2232 (Pasteur scheme). Knockout of tet(X2) in BM4623 restored its susceptibility to tigecycline. Cloning of the tet(X2) gene into Escherichia coli DH5α and Acinetobacter baumannii ATCC 17978 resulted in 16-fold or more increases in MICs of tigecycline. Sequence analysis showed that the region upstream of tet(X2) exhibited a high degree of diversity, while there was a 145 bp conserved region downstream of tet(X2). tet(X2) in BM4623 was located on a novel composite transposon Tn7533, which also contains multiple resistance genes including blaOXA-58. Tn7533 could be excised from the chromosome to form a circular intermediate and transferred into A. baumannii ATCC 17978 by electroporation. Conclusions Our study demonstrates that tet(X2) is a determinant conferring clinical resistance to tigecycline in Acinetobacter species. The emergence of Tn7533 may lead to the potential dissemination of tigecycline and carbapenem resistance in Acinetobacter, which requires continuous monitoring.
ISSN:0305-7453
1460-2091
DOI:10.1093/jac/dkad133