{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T14:01:42Z","timestamp":1787580102439,"version":"build-2736575974"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T00:00:00Z","timestamp":1756252800000},"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:sec><jats:title>Backgroud<\/jats:title><jats:p>The emergence of carbapenem-resistant <jats:italic>Pseudomonas aeruginosa<\/jats:italic> (CRPA) co-producing KPC-2 and VIM-2 has increased the healthcare threats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In this study, a CRPA strain 18102011, was isolated from the bile of a burn patient in ICU of China. Its whole genome was sequenced via the PacBio platform. The molecular characteristics of the genome were analyzed to assess the genetic environment of the carbapenemase genes <jats:italic>bla<\/jats:italic><jats:sub>KPC-2<\/jats:sub> and <jats:italic>bla<\/jats:italic><jats:sub>VIM-2<\/jats:sub>. Antimicrobial susceptibility, plasmid stability, bacterial growth curves, and plasmid conjugation were measured. Strain 18102011 exhibited a resistant pattern to all 23 antibiotics tested, which could be defined as a pan-drug resistant <jats:italic>P. aeruginosa<\/jats:italic> strain. Two plasmids were identified in this strain: the Inc<jats:sub>pRBL16<\/jats:sub> mega-plasmid pP2011\u20131 carrying <jats:italic>bla<\/jats:italic><jats:sub>VIM-2<\/jats:sub> and the IncP6 plasmid pP2011\u20132 carrying <jats:italic>bla<\/jats:italic><jats:sub>KPC-2<\/jats:sub>. <jats:italic>bla<\/jats:italic><jats:sub>VIM-2<\/jats:sub> was located in the region of In2057 (a novel class 1 integron) that was inserted into pP2011-1, and the expression of the <jats:italic>bla<\/jats:italic><jats:sub>VIM-2<\/jats:sub> gene was increased by the PcW<jats:sub>TGN-10<\/jats:sub> promoter located at the 5\u2019-CS. For the <jats:italic>bla<\/jats:italic><jats:sub>KPC-2<\/jats:sub> gene, the core module Tn<jats:italic>3<\/jats:italic>-IS<jats:italic>Kpn27<\/jats:italic>-<jats:italic>bla<\/jats:italic><jats:sub>KPC<\/jats:sub>-\u0394IS<jats:italic>Kpn6<\/jats:italic> served as the <jats:italic>bla<\/jats:italic><jats:sub>KPC-2<\/jats:sub> platform in pP2011-2, and the expression of the <jats:italic>bla<\/jats:italic><jats:sub>KPC-2<\/jats:sub> gene was achieved via the P1 promoter located downstream of IS<jats:italic>Kpn27<\/jats:italic>. This expression pattern resulted in MICs of 4,096 \u03bcg\/mL of imipenem for both strain 18102011 and its transconjugant D2011. Both plasmids were stable in strain 18102011 and could be co-transferred to other strains.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study raised concerns regarding the high stability and non-inferior fitness of <jats:italic>bla<\/jats:italic><jats:sub>KPC-2<\/jats:sub>-<jats:italic>bla<\/jats:italic><jats:sub>VIM-2<\/jats:sub>-CRPA, shed light on its genomic characteristics, and underscored the importance of continued surveillance of CRPA.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2025.1617614","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T04:14:20Z","timestamp":1756268060000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Genomic features and fitness cost of co-existence of blaKPC-2 and blaVIM-2 plasmids in ICU-derived pan-drug resistant Pseudomonas aeruginosa"],"prefix":"10.3389","volume":"15","author":[{"given":"Lin","family":"Zheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gejin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Jing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiwen","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingwei","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejun","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"D690","DOI":"10.1093\/nar\/gkac920","article-title":"CARD 2023: expanded curation, support for machine learning, and resistome prediction at the Comprehensive Antibiotic Resistance Database","volume":"51","author":"Alcock","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"766","DOI":"10.34172\/aim.2020.102","article-title":"Clinical characteristics and outcomes of 905 COVID-19 patients admitted to imam khomeini hospital complex in the capital city of tehran, Iran","volume":"23","author":"Allameh","year":"2020","journal-title":"Arch. 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