BDD vaccine development
We are applying a bioinformatics-centred approach to vaccine design, known as reverse vaccinology, to identify and subsequently evaulate novel BDD vaccine candidates. This approach screens the sequenced genomes of the three most clinically-relevent Treponema spp. for proteins with certain characteristics, including bacterial surface expression and involvement in the infection process, that make them ideal targets as vaccine candidates. Proteins are being synthesised in our laboratory using recombinant DNA technology, and their structure, function and immunogenic properties are being characterised. Vaccine efficacy trials will be conducted in dairy herds.
Host and environmental reservoirs of BDD infection
Since current control stratergies are failing to eliminate BDD and so little little is known about the BDD transmission cycles, our work is attempting to identify potential BDD-associated Treponema spp. infection resevoirs. This is important when designing effective BDD prevention strategies. Our work is employing a variety of molecular and cultivation techniques to screen both different bovine tissues and the farm enviroment for the presence of BDD-associated treponemes.
The characterisation of spirochaetal host-pathogen interactions
We know little of the mechanisms employed by veterinary-relevent spirochates in host colonisation. We are using a variety of bioinformatic and molecular techniques to characterise these mechanisms in clinically-relevent Treponema spp. and Leptospira spp. Particular focus is being given to adhesins, a class of protein expressed on the surface of bacteria that enable adherence to their hosts. These proteins represent potentially vaulable therapeutic targets. In addition, we are focusing our attention on the host cell responses to infection using transcriptomics.
Unravelling the aetiology of contagious ovine digital dermatitis
Our research into the aetiology of CODD has led us to believe that a specific microbial consortium is responsible, but we do not yet know which organisms and necessary for disease onset. Here at Liverpool, we are invesitgating how bacterial populations in CODD lesions change over the course of the infection, as well as the immunological response to these organisms, in an attempt to more fully understand the bacterial nature of CODD.
BDD and CODD: reducing the risk of indirect transmission
We know that both BDD and CODD have an infectious aetiology and transmission between animals is typically rapid. Several studies have revealed risk factors for disease, amougst which, hoof trimming practices, including a failure to sterilise hoof-trimming equipment between animals, has been shown in increase the risk of digital dermatitis development. We are investigating the biological factors (e.g. bacterial survival time and bacterial load) which underpin indirect transmission of digital dermatitis between animals. We are also invesitgating the most appropriate methods of inaminate object sterilisation, particularly the sterilisation of trimming knives/clippers, and how the use of disposable gloves by farm works and veternarians impacts the risk of transmission between animals.
BDD and CODD-associated troponemes: microbiological, molecular and antimicrobial investigations
Our group have developed a selective media isolation method which we have used to isolate >100 digital dermatitis-associated treponemes. Our early work focused on the taxonomic appraisal of these pathogenic isolates into three phylogroups, and we we described the clinical and pathogenic implications. We have also developed an in vitro antimicrobial suceptibility testing method and subsequently identified the most effective antibiotics to guide treatment protocols. Our work in these areas continues. For example, we are currently focusing on defining the genetic similarities and differences that exist between the DD-associated treponemes and human pathogenic treponemes, including genes related to metabolism and virulence.
Other treponeme-mediated dermatological disorders
A substantial and growing body of evidence is emerging to indicate the the treponemes originally associated only with BDD are also associated with a skin lesions in pigs, a newly reported hoof disease in wild North American Elk, bovine ulcerative mammary dermatitis, bovine ischemic teat necrosis and bovine pressure sores. These organisms have also been detected in horse canker lesions and a skin lesion in a sheep. Studies demonstrate that both the host and tissue range considered to be suceptible to infection by these treponemes has expanded. We are attempting to characterise the aetiopathological role of the digital dermatitis-associated treponemes in these infections, and in particular, to understand whether these treponemes are primary or secondary invaders.
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