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

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 sug-
gests 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 clini-
cal 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 activ-
ity 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 We detected blaOXA-347 in a canine isolate and, for the first time, in a clinical C. canimorsus isolate from human
infection. Additionally, we identified a previously uncharacterized allele, newly designated blaOXA-1422, in another clinical
isolate. Both β-lactamases were chromosomally encoded without clear mobile genetic elements and were part of a dis-
tinct 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.