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<p>The increasing prevalence of drug-resistant <i>P. aeruginosa</i> 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 <i>bla</i>OXA-101 and <i>bla</i>OXA-847, in <i>P. aeruginosa</i>. The co-occurrence of <i>bla</i>OXA-101 with OXA-50-like variants exhibited distinct lineage-specific patterns, with <i>bla</i>OXA-101–<i>bla</i>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 <i>bla</i>OXA-101 conferred β-lactam resistance in a promoter-dependent manner and that co-expression of <i>bla</i>OXA-101 with <i>bla</i>OXA-847 was associated with higher MICs than expression of either gene alone. These findings reveal distinct clonal and genomic associations of <i>bla</i>OXA-101 and demonstrate that its contribution to β-lactam resistance is influenced by promoter strength and co-expression with <i>bla</i>OXA-847.</p><p></p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月4日

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  • Yixin Kang,
  • Lu Xie,
  • Zihan Zhang,
  • Junchang Cui

摘要

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 blaOXA-101 and blaOXA-847, in P. aeruginosa. The co-occurrence of blaOXA-101 with OXA-50-like variants exhibited distinct lineage-specific patterns, with blaOXA-101–blaOXA-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 blaOXA-101 conferred β-lactam resistance in a promoter-dependent manner and that co-expression of blaOXA-101 with blaOXA-847 was associated with higher MICs than expression of either gene alone. These findings reveal distinct clonal and genomic associations of blaOXA-101 and demonstrate that its contribution to β-lactam resistance is influenced by promoter strength and co-expression with blaOXA-847.