{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T14:34:51Z","timestamp":1780410891400,"version":"3.54.1"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:p>The global emergence of multidrug-resistant (MDR) <jats:italic>Klebsiella pneumoniae<\/jats:italic>, particularly carbapenem-resistant <jats:italic>K. pneumoniae<\/jats:italic> (CRKP), presents a severe public health threat, limiting available treatment options. Tigecycline and eravacycline, have been considered a last-resort therapeutic against MDR <jats:italic>Enterobacteriaceae<\/jats:italic>. However, strains were resistant to these antibiotics increased recently. The <jats:italic>tmexCD-toprJ<\/jats:italic>, a plasmid-encoded resistance-nodulation-division (RND)-type efflux pump, has emerged as a critical factor conferring resistance to tigecycline and eravacycline. In this study, we reported the emergence of 11 CRKP isolates harboring <jats:italic>tmexCD-toprJ<\/jats:italic>, isolated from two lung transplant patients in a tertiary hospital in eastern China. Most of the isolates (82%) exhibited high-level resistance to tigecycline and eravacycline, along with other common antibiotics. Whole-genome sequencing (WGS) and phylogenetic analysis indicated these strains are not clonal, and resistance phenotypes were associated with the <jats:italic>tmexCD-toprJ<\/jats:italic> operon and other crucial resistance elements. We also found the <jats:italic>tmexCD-toprJ<\/jats:italic> operon was located on a conjugative plasmid, sharing high sequence similarity with the operon identified in <jats:italic>Pseudomonas aeruginosa.<\/jats:italic> Our results showed that the t<jats:italic>mexCD-toprJ<\/jats:italic>-harboring plasmid is efficiently transferable, which contributes to the dissemination of tigecycline and eravacycline resistance. At the same time, the plasmid can coexist with the <jats:italic>bla<jats:sub>KPC-2<\/jats:sub><\/jats:italic>-carrying plasmid, which may cause multidrug resistance. The emergence of <jats:italic>tmexCD-toprJ<\/jats:italic>-positive CRKP in lung transplant patients highlights the potential for rapid nosocomial dissemination and reduced treatment efficacy of last-line antimicrobials. Our findings emphasize the need for enhanced genomic surveillance, infection control measures, and alternative therapeutic strategies to combat the spread of <jats:italic>tmexCD-toprJ<\/jats:italic>-mediated resistance in clinical settings.<\/jats:p>","DOI":"10.3389\/fcimb.2025.1579880","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T05:42:33Z","timestamp":1745991753000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Emergence and dissemination of multidrug-resistant Klebsiella pneumoniae harboring the novel tmexCD-toprJ RND efflux pump operon"],"prefix":"10.3389","volume":"15","author":[{"given":"Haojin","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingjie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meilan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiyao","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cailing","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiana","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihua","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyou","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"key":"B1","volume-title":"Antibiotic resistance threats in the United States, 2019","year":"2019"},{"key":"B2","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.ijmm.2013.02.001","article-title":"Plasmids and the spread of resistance","volume":"303","author":"Carattoli","year":"2013","journal-title":"Int. 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