Genomic insights into the diversity, antimicrobial resistance and zoonotic potential of Campylobacter fetus across diverse hosts and geographies

Introduction. Campylobacter fetus causes reproductive diseases in livestock and can lead to zoonotic infections such as bacteraemia, particularly in immunocompromised individuals. Despite its significance, its genomic characteristics remain poorly understood. This study analysed 114 publicly available C. fetus genomes to provide global insights into genetic diversity, antimicrobial resistance (AMR) and zoonotic risk. Results. A total of 32 distinct sequence types (STs) were identified across 111 of the 114 C . fetus genomes, spanning 6 continents and diverse hosts (cattle, humans, sheep and reptiles). The majority of strains from cattle (75.6%, n / N =34/45) were assigned to ST-4, which was the most prevalent overall ( n =45), while human-associated genomes exhibited the highest diversity with 16 STs. C. fetus subsp. venerealis (Cfv) and its biovar intermedius (Cfvi) genomes clustered closely, forming distinct branches at the biovar level; however, six Cfv genomes were located within Cfvi clades, suggesting a shared ancestry. C. fetus subsp. testudinum (Cft), primarily isolated from humans (60.0%, n / N =18/30), exhibited a more diverse genetic profile, with 20 STs. Cfv from North America and Cfvi from South America formed distinct geographic clusters, while C. fetus subsp. fetus genomes showed no clear geographic patterns, indicating global spread. Pangenomic analysis revealed substantial variation in gene presence/absence in Cft. Five AMR genes were detected, with tet(O ) ( n =3) being the most common. A total of 220 plasmid contigs were identified across 47 genomes, predominantly in Cfvi (66.8%, n / N =147/220) and Cfv (29.1%, n / N =64/220). Horizontal gene transfer analysis identified 140 genomic islands across 41 genomes, and virulence factor analysis revealed cheY as the sole conserved virulence gene across 35 genomes. Conclusion. These findings provide critical insights into the genomic diversity, zoonotic potential and global distribution of C. fetus , emphasizing the need for integrated genomic and epidemiological strategies to assess its impact on human and animal health.