Comparative genomics of campylobacter fetus from reptiles and mammals reveals divergent evolution in host-associated lineages

Abstract

Campylobacter fetus currently comprises three recognized subspecies, which display distinct host association. Campylobacter fetus subsp. fetus and C. fetus subsp. venerealis are both associated with endothermic mammals, primarily ruminants, whereas C. fetus subsp. testudinum is primarily associated with ectothermic reptiles. Both C. fetus subsp. testudinum and C. fetus subsp. fetus have been associated with severe infections, often with a systemic component, in immunocompromised humans. To study the genetic factors associated with the distinct host dichotomy in C. fetus,whole-genome sequencing and comparison ofmammal- and reptileassociated C. fetus was performed. The genomes of C. fetus subsp. testudinum isolated from either reptiles or humans were compared with elucidate the genetic factors associated with pathogenicity in humans. Genomic comparisons showed conservation of genecontent andorganizationamongC. fetus subspecies,but a clear distinctionbetweenmammal-andreptile-associatedC. fetus was observed. Several genomic regions appeared to be subspecies specific, including a putative tricarballylate catabolism pathway, exclusively present in C. fetus subsp. testudinum strains. Within C. fetus subsp. testudinum, sapA, sapB, andsapAB type strainswere observed. Therecombinant locusiamABC(mlaFED)was exclusively associatedwithinvasiveC. fetus subsp. testudinumstrains isolated fromhumans.Aphylogenetic reconstructionwas consistent with divergent evolution in host-associated strains and the existence of a barrier to lateral gene transfer between mammal- and reptile-associated C. fetus. Overall, this study shows that reptile-associated C. fetus subsp. testudinum is genetically divergent from mammal-associated C. fetus subspecies.