Comparative genomics of the Campylobacter genus: Insights into phylogenomics, virulence, genome plasticity and resistome profiling

Campylobacter species are major contributors to foodborne and waterborne zoonotic gastroenteritis. Several species, including C. jejuni, C. coli, C. fetus, C. concisus, C. lari, C. hyointestinalis, C. upsaliensis , and C. hepaticus , are established pathogens, while the pathogenic potential of other members remains unclear. This study presents a comparative genomics analysis of the fifty reported species of Campylobacter genus, encompassing phylogenomic relationships, functional repertoire profiling, virulence genes, diversity of Cytolethal distending toxin gene ( Cdt ), outer membrane components, genome plasticity, and resistome characterization. Phylogenetic analyses revealed that C. hepaticus, C. taniopygae , and C. iguaniorum , traditionally considered non-pathogenic or minor pathogens, cluster with major pathogenic species, suggesting shared evolutionary features. Functional repertoire profiling indicated metabolic flexibility that supports environmental adaptability, while virulence profiling highlighted both conserved and species-specific determinants. Variation in Cdt genes and outer membrane components emerged as key factors in pathogenicity. Notably, C. helveticus shows potential to emerge as a significant pathogen, whereas C. vicugnae and C. vulpis display close evolutionary relationships with C. jejuni . Genome plasticity analyses identified horizontal gene transfer via genomic islands, prophage insertions, and CRISPR arrays, underscoring the dynamic evolution of virulence traits. Resistome characterization revealed widespread antimicrobial resistance genes, raising concerns about multidrug resistance and clinical management. Overall, this study provides an integrative framework to understand the evolutionary dynamics, virulence potential, and antimicrobial resistance of Campylobacter , offering valuable insights for surveillance and therapeutic strategies.