β-lactamase genes in clinical isolates of Capnocytophaga canimorsus and description of a novel class D β-lactamase, OXA-1422

Abstract

BACKGROUND: Capnocytophaga canimorsus (C. canimorsus) is a zoonotic pathogen transmitted by dogs and cats that can cause severe infections in humans. Antimicrobial susceptibility data remain limited, but increasing genomic evidence suggests that functional β-lactamase genes may be more widespread than previously recognized. METHODS: Three C. canimorsus isolates harboring class D β-lactamase genes were selected by genomic screening from a larger collection of the Global Capnocytophaga Consortium for detailed characterization: two isolates from human clinical infections from Sweden and New Zealand, and a commensal canine isolate from the Czech Republic. We used hybrid Illumina-Nanopore genome assemblies, phylogenetic analysis, and structural modeling to characterize the genomic context and the predicted protein features of the β-lactamase genes. The functional impact of the β-lactamases on antibiotic activity was assessed by minimum inhibitory concentration (MIC) testing and confirmed through recombinant expression in the β-lactamase-negative reference strain C. canimorsus 5 (Cc5). RESULTS: , in another clinical isolate. Both β-lactamases were chromosomally encoded without clear mobile genetic elements and were part of a distinct phylogenetic cluster within the OXA family. Structural modeling showed conserved class D β-lactamase architecture. Strains carrying either gene had elevated MICs for multiple β-lactams, and expression of each gene in Cc5 recapitulated these effects. CONCLUSIONS: The identification and phenotypic characterization of OXA-type β-lactamases in clinical C. canimorsus isolates refine our understanding of β-lactamase diversity in this species and underscore the need for systematic investigations of β‑lactamase prevalence in this zoonotic pathogen.