YI-CHYI LAI2026-10-162026-10-162026-01-01Pure ID: 15275988Pure UUID: aa64a00e-d698-4f86-b0c5-6d4b59e46c6a10.1099/mgen.0.001694https://www.scopus.com/pages/publications/105036456942https://scholars.csmu.edu.tw/handle/123456789/26149The global rise of carbapenem-resistant Pseudomonas aeruginosa (CRPA) poses a significant threat to public health. Through active surveillance conducted between 2021 and 2022, we collected 92 distinct CRPA isolates and identified a clonal shift toward high-risk lineages ST235* and ST292. Whole-genome sequencing and phylogenomic analysis revealed that ST235*, a single-locus variant of epidemic ST235, exhibited broader antimicrobial resistance (AMR) and carried a nalD loss-of-function mutation, resulting in MexAB-OprM overexpression. Two ST235* isolates contained a hybrid resistance cassette with blaKPC-2 and blaTEM-1, likely acquired through IS26-mediated transfer from Enterobacter hormaechei. Most ST292 isolates demonstrated an extensively drug-resistant phenotype with a blaCARB-2-containing cassette and a chromosomally integrated tMexC3D-OprJ efflux system. Additionally, ST244 isolates possessed a blaVIM-2 cassette embedded within a Tn402 transposition module (tniABQRintI1). Multiple copies of tniABQR-intI1 carrying AMR genes were exclusively found in the genomes of ST244, representing a novel mechanism. The genomic plasticity of high-risk CRPA lineages emphasizes their capacity to acquire, amplify and disseminate AMR determinants. To combat the spread of CRPA, genomic surveillance and targeted infection control strategies are urgently required.enjournal article