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.

Amplification of acidic protease virulence gene (aprV2) in samples from footrot lesions did not help in diagnosis of clinical virulent footrot in affected sheep flocks in New South Wales

“…7 This single amino acid difference in the acidic protease gene has been used to separate 103 global isolates of D. nodosus into two clades, which correlate with known virulent and benign phenotypes. 20 However, in our study the ratio of virulent to total D. nodosus determined by the apr qPCRs did not increase with increasing foot lesion severity based on 44 sheep flocks from 36 NSW properties sampled from September 2015 to April 2016. The expression of footrot in sheep relies not only on the virulence of the D. nodosus infecting strains, but also on host genetics, immunity and environmental conditions.…”

Infectious lameness among migratory sheep and goats in north-west India, with particular focus on anaerobes

“…The latter encodes for arginine instead of tyrosine at position 92 in the mature AprV2 protease, which allows direct detection and differentiation of virulent and benign D. nodosus from interdigital skin swabs in a single test. The recent findings (40), based on analysis of the genomes of 103 isolates of D. nodosus from different regions of the world, has revealed a bimodal population structure that is globally conserved. This data provided evidence that virulent and benign isolates represent two distinct forms of D. nodosus strains correlating perfectly with the single amino acid difference between the AprV2 and AprB2 protease.…”

Klaueninfektionen beim Schaf – Therapiemöglichkeiten in der tierärztlichen Praxis unter besonderer Berück sichtigung der Moderhinkebekämpfung

“…Diese wiederum kodieren thermostabile bzw. thermolabile Proteasen, die als Virulenzfaktoren von Bedeutung sind (50). So kann in kurzer Zeit aus Nativpräparaten die Beteiligung virulenter Stämme nachgewiesen werden (75).…”