Global epidemiology, genomic context, and functional characterization of blaOXA-101 in association with OXA-50-like β-lactamases in Pseudomonas aeruginosa

The increasing prevalence of drug-resistant P. aeruginosa poses a major challenge in management. OXA-type β-lactamases, particularly OXA-10-like and OXA-50-like variants, contribute to β-lactam resistance, yet their epidemiological distribution and functional interactions remain incompletely understood. We performed an integrated analysis combining large-scale genomic data, phylogenetic analysis, and functional assays to investigate the distribution, clonal association, genomic context, and resistance profiles of OXA-10-like and OXA-50-like β-lactamases, with a focus on bla OXA-101 and bla OXA-847, in P. aeruginosa . The co-occurrence of bla OXA-101 with OXA-50-like variants exhibited distinct lineage-specific patterns, with bla OXA-101– bla OXA-847 combinations associated with ST244. Computational prediction of genomic localization suggested heterogeneous configurations, including chromosome–chromosome, chromosome–plasmid, and plasmid–plasmid arrangements. Functional assays demonstrated that bla OXA-101 conferred β-lactam resistance in a promoter-dependent manner and that co-expression of bla OXA-101 with bla OXA-847 was associated with higher MICs than expression of either gene alone. These findings reveal distinct clonal and genomic associations of bla OXA-101 and demonstrate that its contribution to β-lactam resistance is influenced by promoter strength and co-expression with bla OXA-847.