What really causes footrot in sheep: a national cohort study of the microbial diversity of Dichelobacter nodosus in sheep in sickness and in health

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There are a plethora of virulent factors in Dicelobacter nodosus, the causal agent of ovine footrot, but these do not clearly define benign and virulent strains. The disease itself is endemic or epidemic in different climates suggesting a complex aetiology. We consider that only by studying D. nodosus using non-culture methods will we understand the dynamic relationship between colonisation, bacterial virulence and disease episodes in sheep. Given the persistent nature of D. nodosus, understanding this relationship is essential to develop strategies for control of disease, including better vaccines. This PhD will explore the range of virulence factors in the community of D. nodosus in flocks of sheep, to test the hypothesis that in endemic situations a community of D. nodosus strains are distributed nationally and that control can be obtained by targeted management of strains at a national level.Experimental approachesThe student will source swab samples from farmers throughout England who will also send data from their sheep, including estimated level of footrot and ID.Methodology and study design1. Use epidemiological principles to design the sampling protocol and study to collect a sample of swabs from a representative number of English sheep farmers who responded to our recent study (700 farmers) in years 1 and 2, conduct the study and receive the swab samples (24 months)2. Learn molecular methods and investigate serogroup and virulence factors in the community of D. nodosus strains collected (30 months)3. Use modelling to test the hypothesis that serogroup and virulence are associated with spatial clustering of sheep in England and farmer behaviour in terms of biosecurity and purchase of sheep. ( 36 months)4. Identify the most prevalent serogroups and test the hypothesis that a serogroup specific vaccine could be used to control footrot in England. The ultimate aim is to identify the relative proportion of to 10 serogroups of D. nodosus and to investigate whether a vaccine with fewer serogroups could be used to control footrot in sheep.Molecular trainingThe student will extract DNA from interdigital matter on stored swabs. They will identify all serogroups and fimbrial load of each serogroup by qPCR and use specific primers to investigate the presence of virulence factors (e.g. fimA, aprV2; Keenan et al., 2011).Statistical and epidemiological modellingThe student will use mixed effect multistate models and latent class models in a Bayesian framework, that allows prediction and inference, to identify patterns within the community of D. nodosus virulence factors and distribution of D. nodosus nationally.Originality: The national community of D. nodosus has never been studied before with analysis of strains of bacteria using epidemiological data, this is highly novel for any disease.Difficulties: Developing skills to do the molecular biology will take time and having several strains in a sample will require consideration on how to summarise the data for further analysis.Challenges: How to analyse the data from the community strain analysis so that they can be used in statistical modelling of the study.