Characterization of IncHI1B Plasmids Encoding Efflux Pump TmexCD2-ToprJ2 in Carbapenem-Resistant Klebsiella variicola, Klebsiella quasipneumoniae, and Klebsiella michiganensis Strains

作者：Yujiao Wang, Bo Zhu, Min Liu, Xiutao Dong, Jianping Ma, Xiaofeng Li, Fang Cheng, Jianzhuang Guo, Sumei Lu, Furong Wan, Yingying Hao, Wanshan Ma, Mingju Hao, Liang Chen · 发表于：Frontiers in Microbiology · 年份：2021 · DOI：10.3389/fmicb.2021.759208 · 被引用次数：43 · 研究领域：Antibiotic Resistance in Bacteria、Pharmaceutical and Antibiotic Environmental Impacts、Antibiotics Pharmacokinetics and Efficacy

Tigecycline serves as one of the last-resort antibiotics to treat severe infections caused by carbapenem-resistant Enterobacterales. Recently, a novel plasmid-mediated resistance-nodulation-division (RND)-type efflux pump gene cluster, TmexCD1-ToprJ1 , and its variants, TmexCD2-ToprJ2 and TmexCD3-ToprJ3 , encoding tetracyclines and tigecycline resistance, were revealed. In this study, we reported three TmexCD2-ToprJ2 -harboring Klebsiella species strains, collected from two teaching tertiary hospitals in China, including one K. quasipneumoniae , one K. variicola , and one K. michiganensis . The three strains were characterized by antimicrobial susceptibility testing (AST), conjugation assay, WGS, and bioinformatics analysis. AST showed that K. variicola and K. quasipneumoniae strains were resistant to tigecycline with MIC values of 4μg/ml, whereas the K. michiganensis was susceptible to tigecycline with an MIC value of 1μg/ml. The TmexCD2-ToprJ2 clusters were located on three similar IncHI1B plasmids, of which two co-harbored the metallo-β-lactamase gene bla NDM-1 . Conjugation experiments showed that all three plasmids were capable of self-transfer via conjugation. Our results showed, for the first time, that this novel plasmid-mediated tigecycline resistance mechanism TmexCD2-ToprJ2 has spread into different Klebsiella species, and clinical susceptibility testing may fail to detect. The co-occurrence of bla NDM-1 and TmexCD2-ToprJ2 in the same plasmid is of particular publi...