{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T02:32:45Z","timestamp":1781058765727,"version":"3.54.1"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T00:00:00Z","timestamp":1633478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats: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, <jats:italic>TmexCD1-ToprJ1<\/jats:italic>, and its variants, <jats:italic>TmexCD2-ToprJ2<\/jats:italic> and <jats:italic>TmexCD3-ToprJ3<\/jats:italic>, encoding tetracyclines and tigecycline resistance, were revealed. In this study, we reported three <jats:italic>TmexCD2-ToprJ2<\/jats:italic>-harboring <jats:italic>Klebsiella<\/jats:italic> species strains, collected from two teaching tertiary hospitals in China, including one <jats:italic>K. quasipneumoniae<\/jats:italic>, one <jats:italic>K. variicola<\/jats:italic>, and one <jats:italic>K. michiganensis<\/jats:italic>. The three strains were characterized by antimicrobial susceptibility testing (AST), conjugation assay, WGS, and bioinformatics analysis. AST showed that <jats:italic>K. variicola<\/jats:italic> and <jats:italic>K. quasipneumoniae<\/jats:italic> strains were resistant to tigecycline with MIC values of 4\u03bcg\/ml, whereas the <jats:italic>K. michiganensis<\/jats:italic> was susceptible to tigecycline with an MIC value of 1\u03bcg\/ml. The <jats:italic>TmexCD2-ToprJ2<\/jats:italic> clusters were located on three similar IncHI1B plasmids, of which two co-harbored the metallo-\u03b2-lactamase gene <jats:italic>bla<\/jats:italic><jats:sub>NDM-1<\/jats:sub>. Conjugation experiments showed that all three plasmids were capable of self-transfer <jats:italic>via<\/jats:italic> conjugation. Our results showed, for the first time, that this novel plasmid-mediated tigecycline resistance mechanism <jats:italic>TmexCD2-ToprJ2<\/jats:italic> has spread into different <jats:italic>Klebsiella<\/jats:italic> species, and clinical susceptibility testing may fail to detect. The co-occurrence of <jats:italic>bla<\/jats:italic><jats:sub>NDM-1<\/jats:sub> and <jats:italic>TmexCD2-ToprJ2<\/jats:italic> in the same plasmid is of particular public health concern as the convergence of \u201cmosaic\u201d plasmids can confer both tigecycline and carbapenem resistance. Its further spread into other clinical high-risk <jats:italic>Klebsiella<\/jats:italic> clones will likely exacerbate the antimicrobial resistance crisis. A close monitoring of the dissemination of <jats:italic>TmexCD-ToprJ<\/jats:italic> encoding resistance should be considered.<\/jats:p>","DOI":"10.3389\/fmicb.2021.759208","type":"journal-article","created":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T12:21:59Z","timestamp":1633609319000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":26,"title":["Characterization of IncHI1B Plasmids Encoding Efflux Pump TmexCD2-ToprJ2 in Carbapenem-Resistant Klebsiella variicola, Klebsiella quasipneumoniae, and Klebsiella michiganensis Strains"],"prefix":"10.3389","volume":"12","author":[{"given":"Yujiao","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiutao","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianzhuang","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumei","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Furong","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanshan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingju","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,6]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: a flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"8365","DOI":"10.1038\/srep08365","article-title":"RASTtk: a modular and extensible implementation of the RAST algorithm for building custom annotation pipelines and annotating batches of genomes","volume":"5","author":"Brettin","year":"2015","journal-title":"Sci. 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