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

item GILBERT, MAARTEN - Utrecht University
item Miller, William - Bill
item Yee, Emma
item ZOMER, ALDERT - Utrecht University
item VAN DER GRAAF, LINDA - Utrecht University
item FITZGERALD, COLLETTE - Chinese Center For Disease Control
item FORBES, KENNETH - University Of Aberdeen
item MERIC, GUILLAUME - Swansea University
item SHEPPARD, SAMUEL - Swansea University
item WAGENAAR, JAAP - Utrecht University
item DUIM, BIRGITTA - Utrecht University

Submitted to: Genome Biology and Evolution
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/2/2016
Publication Date: 6/22/2016
Citation: Gilbert, M.J., Miller, W.G., Yee, E., Zomer, A., van der Graaf, L., Fitzgerald, C., Forbes, K.J., Meric, G., Sheppard, S.K., Wagenaar, J.A., Duim, B. 2016. Comparative genomics of Campylobacter fetus from reptiles and mammals reveals divergent evolution in host-associated lineages. Genome Biology and Evolution. 8(6):2006-2019.

Interpretive Summary: The food-borne pathogen Campylobacter is a natural contaminant of most birds and livestock. Campylobacter fetus strains are associated normally with livestock disease and are one of the leading causes of abortions in cattle and sheep. Campylobacter fetus currently contains three defined subspecies: C. fetus subsp. fetus, C. fetus subsp. venerealis and C. fetus testudinum. These subspecies are distinguished by their host range and pathogenicity: C. f. fetus is isolated from different animals and occasionally food, C. f. venerealis is restricted to cattle and is a leading cause of abortions in cattle, and C. f. testudinum is isolated from reptiles and occasionally from human systemic infections. This study aimed to identify subspecies-specific chromosomal features that might be important in determining host range and causation of disease. Although the chromosomal sequences of all three subspecies were highly similar, genomic features were identified in C. f. testudinum that may explain its association with infection in humans. One particular group of genes was isolated exclusively from strains that caused invasive disease in humans. These features were likely acquired via DNA transfer from another pathogenic organism.

Technical Abstract: Campylobacter fetus currently comprises three recognized subspecies: C. fetus subsp. fetus, C. fetus subsp. venerealis, and C. fetus subsp. testudinum, which display a distinct host association. Both C. fetus subsp. fetus and C. fetus subsp. venerealis are 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 of mammal- and reptile-associated C. fetus was performed. The genomes of C. fetus subsp. testudinum isolated from either reptiles or humans were compared to elucidate the genetic factors associated with pathogenicity in humans. Genomic comparisons showed high conservation in gene content and organization amongst C. fetus subspecies, but a clear distinction between mammal- and reptile-associated C. fetus was observed. Several genomic regions appeared to be subspecies specific, including a putative tricarballylate catabolism pathway, exclusively present in all C. fetus subsp. testudinum strains. Within C. fetus subsp. testudinum, sapA, sapB, and sapAB type strains were observed. The recombinant locus iamABC was exclusively associated with invasive C. fetus subsp. testudinum strains isolated from humans. A phylogenomic reconstruction identified divergent evolution in niche preferences and the role of horizontal gene transfer in the speciation of C. fetus. Overall, this study shows that reptile-associated C. fetus subsp. testudinum is genetically deviant from mammal-associated C. fetus subspecies.