Dissecting the molecular diversity of bovine digital dermatitis treponemes.

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Bovine Digital Dermatitis (BDD) is a lameness of cattle present in the majority of dairy herds in the UK and reported throughout the world. This lameness is the result of inflamed lesions between the heel bulbs of the rear feet. The disease is of particular significance because it is very painful for the animal affected resulting in poor animal welfare. Despite some response to commonly used antibiotics, lesions frequently reappear. The disease is an important global food security issue because it causes reduction in milk production and poor reproductive performance in dairy cows. Furthermore, with the recent cost to the dairy industry in the UK likely to be as much as 26 million pounds per year, it has a negative effect the UK's economic competitiveness. The disease has now been identified in sheep, where it is known as Contagious Ovine Digital Dermatitis (CODD) with lesions more severe than seen in cattle with frequent reports of complete hoof loss. BDD has been identified as an infectious disease with a bacterial cause. The majority of evidence clearly identifies bacteria known as 'Treponema' as the common cause of BDD. Previous studies at the University of Liverpool have clarified the association of these bacteria with BDD and characterised these causal bacteria into three distinct groups. These studies have allowed for the isolation of 70 treponemes from BDD lesions, a greater number than any other research groups working on this disease worldwide. This strain collection is an invaluable resource for investigating how these organisms produce such severe disease in cattle and sheep and how the infection may so readily be transmitted between animals. The proposed research in this current grant application will use this large panel of isolates to investigate how these organisms cause the disease in cattle and whether novel vaccines or treatments can be developed. The three distinct groups of bacteria (treponemes) are very different from one another in terms of their genetics and their actual characteristics yet they are all able to colonise the bovine hoof and cause disease. Whilst the different treponeme groups may be quite diverse, to be able to share the same 'niche', they may still share very similar machinery to be able to grow, survive and damage the cow. This common machinery is likely to be proteins exhibited on the surface of the cell which are responsible for binding or damaging the host and if shared across all BDD treponemes may have potential as vaccine targets. Identification of these key bacterial proteins and determining whether they interact with the host immune system allows for identification of potential vaccine components and thus enable a strategy to prevent disease in cattle and sheep herds.At the University of Liverpool, there have been major investments in the current cutting edge technologies of genomics and proteomics and with these facilities it is now possible to perform substantial experiments not previously possible. For example, whole genomes of these treponemes can now be generated in a relatively short time. This study proposes to use this cutting edge sequencing technology to investigate, on a large scale all the predicted disease causing characteristics of the bacteria. To confirm that the genes identified are in fact expressed the proteomics approaches will be used to identify all the proteins both inside the treponemes and those on the surface. Furthermore cattle sera will be incubated with the bacterial cell surface proteins to identify which cell surface proteins are bound to by antibodies and therefore to actually identify which are detected by the cattle's immune system. These studies will help characterise the causal bacteria and further aid in potential vaccine design. By investigating BDD using the various methods described above, we should improve understanding of the disease and contribute towards the eradication of this painful and expensive disease.