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Life sciences · Journal article
Genome Medicine · November 3, 2026
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The dissemination of carbapenem-resistant Pseudomonas aeruginosa (CRPA) across human, environmental, and agricultural interfaces represents an increasing One Health challenge. We analyzed 716 P. aeruginosa isolates collected over four seasons from hospitals, farms, and wastewater treatment plants in five provinces of China using whole-genome sequencing, clonal network analysis, and comparative genomics. Among the collected isolates, 477 (66.62%) isolates were identified as CRPA, comprising 63 carbapenemase-producing CRPA (CP-CRPA) and 414 non-carbapenemase-producing CRPA isolates. Despite substantial population diversity, comprising 189 known and 9 novel sequence types (STs), clonal dissemination was highly concentrated within specific epidemic lineages. Four major putative clonal clusters, dominated by ST381, ST360, ST463, and ST244, persisted across seasons in multiple hospitals. Clonal dissemination occurred predominantly within and between hospitals, with ST463 contributing prominently to possible inter-provincial dissemination, whereas potential cross-sector clonal links were limited to a small number of clusters connecting hospitals with farms or wastewater treatment plants. ST463 was strongly associated with CP-CRPA (26/31, 83.87%) and mainly carried bla KPC-2 on IncU plasmids with a conserved NTE-KPC structure (IS 26 -IS Kpn6 - bla KPC-2 -IS Kpn27 -IS 26 ). Analysis of publicly available genomes suggested that NTE-KPC elements facilitated the expansion of bla KPC-2 across diverse P. aeruginosa lineages in China. Multiple clones were frequently detected in hospital wastewater before or concurrently with detection of the same clones in clinical samples, supporting wastewater as a complementary matrix for genomic surveillance. We further developed a multidimensional framework for assessing hospital-level CRPA risk. Our findings identify hospitals as the predominant settings for CRPA clonal dissemination and highlight the potential of integrating wastewater surveillance and genomic risk assessment to support earlier detection and targeted infection-control interventions.