title: Genomic evidence for a globally distributed, bimodal population in the ovine footrot pathogen Dichelobacter nodosus.
abstract: Footrot is a contagious, debilitating disease of sheep, causing major economic losses in most sheep-producing countries. The causative agent is the Gram-negative anaerobe Dichelobacter nodosus. Depending on the virulence of the infective bacterial strain, clinical signs vary from a mild interdigital dermatitis (benign footrot) to severe underrunning of the horn of the hoof (virulent footrot). The aim of this study was to investigate the genetic relationship between D. nodosus strains of different phenotypic virulences and between isolates from different geographic regions. Genome sequencing was performed on 103 D. nodosus isolates from eight different countries. Comparison of these genome sequences revealed that they were highly conserved, with >95% sequence identity. However, single nucleotide polymorphism analysis of the 31,627 nucleotides that were found to differ in one or more of the 103 sequenced isolates divided them into two distinct clades. Remarkably, this division correlated with known virulent and benign phenotypes, as well as with the single amino acid difference between the AprV2 and AprB2 proteases, which are produced by virulent and benign strains, respectively. This division was irrespective of the geographic origin of the isolates. However, within one of these clades, isolates from different geographic regions generally belonged to separate clusters. In summary, we have shown that D. nodosus has a bimodal population structure that is globally conserved and provide evidence that virulent and benign isolates represent two distinct forms of D. nodosus strains. These data have the potential to improve the diagnosis and targeted control of this economically significant disease.
  
  
  OBJECTIVE
  The Gram-negative anaerobic bacterium Dichelobacter nodosus is the causative agent of ovine footrot, a disease of major importance to the worldwide sheep industry. The known D. nodosus virulence factors are its type IV fimbriae and extracellular serine proteases. D. nodosus strains are designated virulent or benign based on the type of disease caused under optimal climatic conditions. These isolates have similar fimbriae but distinct extracellular proteases. To determine the relationship between virulent and benign isolates and the relationship of isolates from different geographical regions, a genomic study that involved the sequencing and subsequent analysis of 103 D. nodosus isolates was undertaken. The results showed that D. nodosus isolates are highly conserved at the genomic level but that they can be divided into two distinct clades that correlate with their disease phenotypes and with a single amino acid substitution in one of the extracellular proteases.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Kennan
authors.affiliation: Norwegian Veterinary Institute, Oslo, Norway.
authors.forename: Marianne
authors.initials: M
authors.lastname: Gilhuus
authors.forename: Sara
authors.initials: S
authors.lastname: Frosth
authors.forename: Torsten
authors.initials: T
authors.lastname: Seemann
authors.affiliation: Farm Animal and Veterinary Public Health, Faculty of Veterinary Science, the University of Sydney, Camden, New South Wales, Australia.
authors.forename: Om P
authors.initials: OP
authors.lastname: Dhungyel
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Whittington
authors.forename: John D
authors.initials: JD
authors.lastname: Boyce
authors.forename: David R
authors.initials: DR
authors.lastname: Powell
authors.affiliation: Department of Bacteriology, National Veterinary Institute, Uppsala, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Aspán
authors.affiliation: Norwegian Veterinary Institute, Oslo, Norway.
authors.forename: Hannah J
authors.initials: HJ
authors.lastname: Jørgensen
authors.forename: Dieter M
authors.initials: DM
authors.lastname: Bulach
authors.affiliation: julian.rood@monash.edu.
authors.forename: Julian I
authors.initials: JI
authors.lastname: Rood
mesh_terms: D000818:Animals; D001631:Bhutan; D055028:Comparative Genomic Hybridization; D004269:DNA, Bacterial / Q000235:genetics; D020376:Dichelobacter nodosus / Q000235:genetics* / Q000378:metabolism; D010861:Fimbriae, Bacterial / Q000235:genetics; D005535:Foot Rot / Q000382:microbiology*; D016680:Genome, Bacterial; D023281:Genomics; D007194:India; D009390:Nepal; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism; D058974:Phylogeography; D020641:Polymorphism, Single Nucleotide; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D012756:Sheep; D012757:Sheep Diseases / Q000382:microbiology*; D006113:United Kingdom; D037521:Virulence Factors / Q000235:genetics
chemical_list: D004269:DNA, Bacterial; D037521:Virulence Factors; D010447:Peptide Hydrolases; D012697:Serine Endopeptidases