{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T01:23:20Z","timestamp":1778117000042,"version":"3.51.4"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"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>Introduction<\/jats:title><jats:p>The emergence of <jats:italic>Klebsiella<\/jats:italic> pneumoniae carbapenemase (KPC) variants has significantly compromised the efficacy of ceftazidime-avibactam (CZA), a critical antibiotic for treating carbapenem-resistant <jats:italic>K. pneumoniae<\/jats:italic> (CRKP) infections. This study investigates the novel KPC-190 variant, identified in a hypervirulent ST11-K64 <jats:italic>K. pneumoniae<\/jats:italic> strain during CZA therapy, which confers resistance to CZA while partially restoring carbapenem susceptibility.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The <jats:italic>K. pneumoniae<\/jats:italic> clinical isolate LX02 harboring <jats:italic>bla<\/jats:italic><jats:sub>KPC-190<\/jats:sub> was characterized using antimicrobial susceptibility testing, whole-genome sequencing (Illumina and Nanopore), and plasmid analysis. Functional studies included plasmid transformation, cloning assays, and enzyme kinetics (spectrophotometric analysis of purified KPC-190 protein). Genetic context was mapped using bioinformatics tools (RAST, ResFinder, Proksee), and virulence determinants were identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>KPC-190 exhibited a unique resistance profile: high-level CZA resistance (MIC &amp;gt;64 \u03bcg\/mL) with reduced carbapenem MICs (imipenem MIC = 2 \u03bcg\/mL). Enzyme kinetics revealed decreased <jats:italic>K<\/jats:italic>cat\/Km for carbapenems and ceftazidime, alongside a 9-fold higher IC50 for avibactam (0.13 \u03bcM vs. KPC-2\u2019s 0.014 \u03bcM). Genomic analysis identified <jats:italic>bla<\/jats:italic><jats:sub>KPC-190<\/jats:sub> within an IS26 flanked mobile element (IS26-ISKpn8-<jats:italic>bla<\/jats:italic><jats:sub>KPC<\/jats:sub>-\u0394ISKpn6-\u0394tnpR-IS26) on an IncFII plasmid. The strain also carried hypervirulence markers (<jats:italic>rmpA2<\/jats:italic>, <jats:italic>iucABCD-iutA<\/jats:italic>, and type 1\/3 fimbriae).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The KPC-190 variant underscores the adaptive evolution of <jats:italic>bla<\/jats:italic><jats:sub>KPC<\/jats:sub> under antibiotic pressure, combining CZA resistance via enhanced ceftazidime affinity and avibactam evasion with retained carbapenem hydrolysis. Its association with hypervirulence plasmids and IS26-mediated mobility poses a dual threat for dissemination. These findings highlight the urgent need for genomic surveillance and alternative therapies (e.g., meropenem-vaborbactam) to address KPC-190-mediated resistance.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2025.1607127","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T05:23:19Z","timestamp":1749187399000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Evolution of ceftazidime-avibactam resistance driven by variation in blaKPC-2 to blaKPC-190 during treatment of ST11-K64 hypervirulent Klebsiella pneumoniae"],"prefix":"10.3389","volume":"15","author":[{"given":"Zeshi","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Lei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Lei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Geng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingjuan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aili","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.02414-21","article-title":"Structural characterization of the D179N and D179Y variants of KPC-2 \u03b2-lactamase: \u03a9-loop destabilization as a mechanism of resistance to ceftazidime-avibactam","volume":"66","author":"Alsenani","year":"2022","journal-title":"Antimicrob Agents Chemother."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00528-17","article-title":"Klebsiella pneumoniae Carbapenemase-2 (KPC-2), Substitutions at Ambler Position Asp179, and Resistance to Ceftazidime-Avibactam: Unique Antibiotic-Resistant Phenotypes Emerge from \u03b2-Lactamase Protein Engineering","volume":"8","author":"Barnes","year":"2017","journal-title":"mBio"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1007\/s10096-022-04480-x","article-title":"Implementation of Chromatic Super CAZ\/AVI(\u00ae) medium for active surveillance of ceftazidime-avibactam resistance: preventing the loop from becoming a spiral","volume":"41","author":"Bianco","year":"2022","journal-title":"Eur. 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