Integrating clinical, data-driven and in-vitro approaches to the study of host-pathogen interactions in bovine digital dermatitis

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Cattle lameness is a debilitating and painful condition, and is described as one of the clearest indicators of compromised welfare in dairy cattle and one of the most important causes of involuntary removal and replacement of animals. No other common condition is associated with such visible signs of pain and, as such, lameness also damages the public's perception of the industry. Painful foot lesions account for more than 90% of reduced cow mobility and lameness cases. One main cause of cattle lameness is Digital Dermatitis (DD) a painful, infectious, foot skin disease affecting ruminants worldwide. The disease is endemic on more than 90% of UK dairy farms and more than 50% of UK dairy cows are affected annually. In addition to pain and compromised animal welfare, DD is also associated with reduced milk yield, feed intake, and reproductive performance, and estimated to cost the UK dairy industry more than £74 million per year. Bacteria of the genus Treponema are considered the main pathogen associated with DD; however, we still don't fully understand how the disease develops and what the role of the animal's genetics in this is. Current control strategies are mostly generic and lack a substantial evidence base, relying on the empirical use of topical antibiotics and foot-bathing solutions; the latter however often contain heavy metals, such as copper sulphate, or formalin (carcinogen). The use of hazardous chemicals and the increasing evidence for antibiotic resistance in DD treponemes mean current control methods may pose a serious threat to human health and environment. We hypothesise that animal genetics play a key role in the development of DD with resulting differences in animal-pathogen interactions determining the development and progression of the disease. Our overarching goal is to conduct an interdisciplinary, integrated study to further our understanding of the mechanisms leading to the development of DD, investigate animal-pathogen interactions, and determine the optimum evidence based breeding strategy to enhance animal resistance to DD development and animal ability to recover from DD. More specifically we will perform an in-depth characterisation of the genetic background of animal DD phenotypes in order to identify what are the key genes, mutations and cell populations playing an important role in the disease. Moreover, we will investigate the role of animal-pathogen interactions in DD development and progression utilising novel laboratory models of the disease. Finally, we will use all these novel knowledge to develop advanced strategies to control this debilitating disease. A thorough understanding of these mechanisms will underpin modern breeding programmes aiming to reduce incidence of DD and improve recovery from DD, and inform the development of effective targeted treatments by helping to identify novel vaccine and drug targets. This will improve animal health and welfare, potentially reducing further development of antimicrobial resistance, and support the production of healthy food. Associated decrease in involuntary culling of animals and increase in cattle longevity will indirectly contribute to reduction of greenhouse gas emissions and improve the sustainability of the sector. Mounting welfare and cost issues brought about by increasing prevalence of DD in bovine populations both nationally and worldwide demonstrate the timeliness of the proposed project.