Genomic Insights into the Diversity, Antimicrobial Resistance, and Zoonotic Potential of Campylobacter fetus Across Diverse Hosts and Geographies

Abstract Background Campylobacter fetus causes reproductive diseases in livestock and zoonotic infections in humans, especially in immunocompromised individuals. Despite its significance, its genomic characteristics are poorly understood. This study analyzed 114 publicly available C. fetus genomes to provide global insights into its genetic diversity, antimicrobial resistance (AMR) patterns, and zoonotic risk. Results A total of 32 distinct sequence types (STs), ranging from ST-1 to ST-74, were identified across 111 of the 114 C. fetus genomes, spanning six continents and diverse hosts (cattle, humans, sheep, and reptiles). ST-4 was the most prevalent (n = 45), followed by ST-3 (n = 8). A significant proportion (90.9%; n/N=40/44) of C. fetus subsp. venerealis (Cfv) and its biovar intermedius (Cfvi) were assigned to ST-4. Despite being isolated from five continents, Cfv and Cfvi genomes clustered closely, forming distinct branches at the biovar level; however, six Cfv genomes were located within Cfvi clades, suggesting a shared evolutionary lineage. In contrast, C. fetus subsp. testudinum (Cft) genomes, exhibiting 20 distinct STs, formed distinct clades from Cfv, Cfvi, and C. fetus subsp. fetus (Cff). While Cfv genomes from North America and Cfvi genomes from South America formed distinct geographic clusters, Cff genomes displayed no clear geographical patterns, with branches containing strains from multiple continents, indicating a globally dispersed distribution. Pangenomic analysis revealed pronounced clustering within Cft, characterized by unique gene presence/absence patterns. Five distinct AMR genes were detected, with tet(O) (n = 3) being the most common. 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.