{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T08:19:33Z","timestamp":1772180373032,"version":"3.50.1"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"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":"\n Introduction<\/jats:title>\n \n Ceftazidime-avibactam represents a crucial therapeutic option for managing infections attributable to carbapenem-resistant\n P. aeruginosa<\/jats:italic>\n . Nonetheless, the emergence of resistance to ceftazidime-avibactam in\n P. aeruginosa<\/jats:italic>\n presents a significant challenge for clinical anti-infective therapy. This study primarily elucidates the mechanisms by which\n P. aeruginosa<\/jats:italic>\n transitions from drug sensitivity to resistance during ceftazidime-avibactam treatment, ultimately resulting in therapeutic failure.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n The susceptibility testing was performed using the broth microdilution method, conjugation experiment was performed via the filter mating method, the genetic surroundings of\n bla<\/jats:italic>\n KPC-249<\/jats:sub>\n and comparison of plasmids structures was performed using short\/long-read genome sequencing and analysis method, the resistance of transconjugant carried the\n bla<\/jats:italic>\n KPC-249<\/jats:sub>\n to ceftazidime-avibactam was performed via molecular cloning method.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n For\n P. aeruginosa<\/jats:italic>\n isolates from a patient, the minimum inhibitory concentrations (MICs) of ceftazidime-avibactam (CAZ-AVI) were determined as follows: isolates from sputum and bronchoalveolar lavage fluid both exhibited an MIC of 2 mg\/L without blaKPC. In comparison, the blood-isolated strain P. aeruginosa PAE045 showed a significantly elevated MIC of &gt;128 mg\/L against CAZ-AVI. Plasmid conjugation experiments results demonstrated that the plasmid harboring the\n bla<\/jats:italic>\n KPC-249<\/jats:sub>\n gene could be successfully transferred to the recipient strain PAO1\n \n rifR<\/jats:sup>\n <\/jats:italic>\n (rifampicin-resistant\n P. aeruginosa<\/jats:italic>\n PAO1). Third-generation sequencing results revealed that the\n bla<\/jats:italic>\n KPC-249<\/jats:sub>\n gene was located on a plasmid with an approximate size of 37 kb. Compared with the wild-type e\n bla<\/jats:italic>\n KPC-2<\/jats:sub>\n gene, the\n bla<\/jats:italic>\n KPC-249<\/jats:sub>\n gene had two additional amino acid residues in its encoded protein: threonine (Thr, T) at position 182 and serine (Ser, S) at position 183. Furthermore, the upstream and downstream regions of the\n bla<\/jats:italic>\n KPC-249<\/jats:sub>\n gene were flanked by the insertion sequences ISK\n pn6<\/jats:italic>\n and ISK\n pn27<\/jats:italic>\n , respectively.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n These mobile genetic elements may play a role in the capture and dissemination of the\n bla<\/jats:italic>\n KPC-249<\/jats:sub>\n gene. The\n bla<\/jats:italic>\n KPC-249<\/jats:sub>\n gene is identified as a novel mutant variant of the\n bla<\/jats:italic>\n KPC<\/jats:sub>\n gene family, which mediates the resistance of\n P. aeruginosa<\/jats:italic>\n to the antimicrobial agent ceftazidime-avibactam.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1744386","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T06:51:44Z","timestamp":1772175104000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The blaKPC-249-mediated mechanism drives the transition of ST463 Pseudomonas aeruginosa from Ceftazidime-Avibactam sensitivity to resistance during clinical treatment"],"prefix":"10.3389","volume":"16","author":[{"given":"Xiaosi","family":"Li","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, the Second Affiliated Hospital of Jiaxing University","place":["Jiaxing, China"]},{"name":"Department of Laboratory Medicine, Heishui County People's Hospital","place":["Aba Tibetan and Qiang Autonomous, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Jiaxing Maternity and Child Health Care Hospital, College of Medicine, Jiaxing University","place":["Jiaxing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, the Second Affiliated Hospital of Jiaxing University","place":["Jiaxing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heping","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, the Second Affiliated Hospital of Jiaxing University","place":["Jiaxing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shumi","family":"Shang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, the Second Affiliated Hospital of Jiaxing University","place":["Jiaxing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenting","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, the Second Affiliated Hospital of Jiaxing University","place":["Jiaxing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fupin","family":"Hu","sequence":"additional","affiliation":[{"name":"Institute of Antibiotics, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huijun","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, the Second Affiliated Hospital of Jiaxing University","place":["Jiaxing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1007\/s40121-019-0239-0","article-title":"Teaching an old class new tricks: A novel semi-synthetic aminoglycoside, plazomicin","volume":"8","author":"Abdul-Mutakabbir","year":"2019","journal-title":"Infect. 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