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

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

doi:10.3389/fmicb.2021.759208

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

Front Microbiol. 2021 Oct 6:12:759208. doi: 10.3389/fmicb.2021.759208. eCollection 2021.

Authors

Yujiao Wang¹, Bo Zhu², Min Liu³, Xiutao Dong¹, Jianping Ma¹, Xiaofeng Li¹, Fang Cheng¹, Jianzhuang Guo¹, Sumei Lu¹, Furong Wan¹, Yingying Hao⁴, Wanshan Ma¹, Mingju Hao¹, Liang Chen^{5

6}

Affiliations

¹ Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Laboratory Medicine, Jinan, China.
² Xiamen Key Laboratory of Genetic Testing, Department of Laboratory Medicine, The First Affiliated Hospital of Xiamen University, Xiamen, China.
³ Department of Clinical Laboratory, Jinan Dermatosis Prevention and Control Hospital, Jinan, China.
⁴ Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
⁵ Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, United States.
⁶ Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, NJ, United States.

Abstract

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 public health concern as the convergence of "mosaic" plasmids can confer both tigecycline and carbapenem resistance. Its further spread into other clinical high-risk Klebsiella clones will likely exacerbate the antimicrobial resistance crisis. A close monitoring of the dissemination of TmexCD-ToprJ encoding resistance should be considered.

Keywords: Klebsiella michiganensis; Klebsiella quasipneumoniae; Klebsiella variicola; TmexCD2-ToprJ2; blaNDM-1; blaNDM-5; carbapenem resistance; tigecycline resistance.