Background on Dichelobacter nodosus and footrot
Footrot accounts for 90% of lameness in sheep in the UK. Footrot has two presentations, the first being interdigital dermatitis (ID), inflammation and/or lesions of the interdigital skin. This can progress to destruction of the epidermal matrix and separation of the hoof horn from the underlying soft tissue, this is termed severe footrot. ID and severe footrot cause lameness, loss of condition and reduced productivity. The economic impact of lameness is estimated to range between £24 and £80 million per annum. Climate has a significant impact on footrot in the UK and other countries, with prevalence increasing with increasing rainfall and temperature. The recommended treatment is a topical antibacterial spray, and antibacterial injection within three days of sheep becoming lame and not to trim the hoof horn.
The main causative agent of footrot is Dichelobacter nodosus, a Gram negative obligate anaerobe. By observation it is difficult to clinically differentiate between ID that will progress to severe footrot (virulent strains) and ID that is self-limiting (benign strains). The distinction between virulent and benign remains uncertain and one problem is that often multiple D. nodosus strains are isolated, so apparently benign strains may be detected on farms with severe footrot.
A number of virulence factors have been identified in D. nodosus, including extracellular serine proteases, type IV fimbriae and the intergrase A gene. But their association with virulence has varied in both their role and the certainty of their contribution towards virulence. The aims for this project are to investigate the D. nodosus strain community and the virulence factors of D. nodosus to discover how both of these link with the severity of footrot observed on the feet of sheep. Virulence factors have been a key feature in recent literature relating to ovine footrot, however there is little certainty of the true strength of the relationship between these virulence factors and the severity of the disease observed on the foot.
I am using foot swabs from Smith et al. (2014) who studied 99 sheep on one farm over a period of 10 months. Lameness, ID and footrot scores were recorded during four 4-week periods. Swabs of the interdigital skin and lesions were taken. Fifty of these ewes underwent genomic study for a paper in preparation by Smith et al. where the serogroups were identified and dominant D. nodosus strains were found to persist over time. I am using the non-culture technique of quantitative PCR to detect D. nodosus. I will compare these results with the data from cultured D. nodosus isolates obtained from the previous study to test the hypothesis that investigation of the whole community of D. nodosus will elucidate the role of virulence factors in disease severity in an endemic situation.
I am collaborating with the Centre for Genomic Pathogen Surveillance group at the Wellcome Sanger Institute to sequence the whole genome of D. nodosus isolates from the one farm I have been studying and also other D. nodosus isolates from around the UK and worldwide. This will allow me to investigate disease transmission and the virulence factors of D. nodosus and also look into geographical patterns. This will help to gain a better understanding of the D. nodosus community and virulence factors and their roles in the pathogenesis of footrot.
SMITH, E. M., GREEN, O. D. J., CALVO-BADO, L. A., WITCOMB, L. A., GROGONO-THOMAS, R., RUSSELL, C. L., BROWN, J. C., MEDLEY, G. F., KILBRIDE, A. L., WELLINGTON, E. M. H. & GREEN, L. E. (2014) Dynamics and impact of footrot and climate on hoof horn length in 50 ewes from one farm over a period of 10 months. Veterinary Journal, 201, 295-301.
SMITH, E. M., GILBERT, A., RUSSELL, C. L., PURDY, K. J., MEDLEY, G. F., MUZAFAR, M., GROGONO-THOMAS, R. & GREEN, L. E. (2017) Within-Flock Population Dynamics of Dichelobacter nodosus. Frontiers in Veterinary Sciences, 4(58).
KENNAN, R. M., GILHUUS, M., FROSTH, S., SEEMANN, T., DHUNGYEL, O. P., WHITTINGTON, R. J., BOYCE, J. D., POWELL, D. R., ASPAN, A., JORGENSEN, H. J., BULACH, D. M. & ROOD, J. I. (2014) Genomic Evidence for a Globally Distributed, Bimodal Population in the Ovine Footrot Pathogen Dichelobacter nodosus. mBio, 5(5).
BLANCHARD, A. M., JOLLEY, K. A., MAIDEN, M. C. J., COFFEY, T. J., MABONI, G., STALEY, C. E., BOLLARD, N. J., WARRY, A., EMES, R. D., DAVIES, P. L. & TOTEMEYER, S. (2018) The Applied Development of a Tiered Multilocus Sequence Typing (MLST) Scheme for Dichelobacter nodosus. Frontiers in Microbiology, 9(551).