AUTHOR=Wang Yujiao , Zhu Bo , Liu Min , Dong Xiutao , Ma Jianping , Li Xiaofeng , Cheng Fang , Guo Jianzhuang , Lu Sumei , Wan Furong , Hao Yingying , Ma Wanshan , Hao Mingju , Chen Liang 

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

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.759208

DOI=10.3389/fmicb.2021.759208

ISSN=1664-302X

ABSTRACT=<p>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, <italic>TmexCD1-ToprJ1</italic>, and its variants, <italic>TmexCD2-ToprJ2</italic> and <italic>TmexCD3-ToprJ3</italic>, encoding tetracyclines and tigecycline resistance, were revealed. In this study, we reported three <italic>TmexCD2-ToprJ2</italic>-harboring <italic>Klebsiella</italic> species strains, collected from two teaching tertiary hospitals in China, including one <italic>K. quasipneumoniae</italic>, one <italic>K. variicola</italic>, and one <italic>K. michiganensis</italic>. The three strains were characterized by antimicrobial susceptibility testing (AST), conjugation assay, WGS, and bioinformatics analysis. AST showed that <italic>K. variicola</italic> and <italic>K. quasipneumoniae</italic> strains were resistant to tigecycline with MIC values of 4μg/ml, whereas the <italic>K. michiganensis</italic> was susceptible to tigecycline with an MIC value of 1μg/ml. The <italic>TmexCD2-ToprJ2</italic> clusters were located on three similar IncHI1B plasmids, of which two co-harbored the metallo-β-lactamase gene <italic>bla</italic><sub>NDM-1</sub>. Conjugation experiments showed that all three plasmids were capable of self-transfer <italic>via</italic> conjugation. Our results showed, for the first time, that this novel plasmid-mediated tigecycline resistance mechanism <italic>TmexCD2-ToprJ2</italic> has spread into different <italic>Klebsiella</italic> species, and clinical susceptibility testing may fail to detect. The co-occurrence of <italic>bla</italic><sub>NDM-1</sub> and <italic>TmexCD2-ToprJ2</italic> 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 <italic>Klebsiella</italic> clones will likely exacerbate the antimicrobial resistance crisis. A close monitoring of the dissemination of <italic>TmexCD-ToprJ</italic> encoding resistance should be considered.</p>