About the Project
Ovine footrot, bovine foul-in-the-foot, superfoul, interdigital fibroma and heel erosion are economically important foot infections of farmed ruminants, causing significant pain and suffering in affected animals. Ovine footrot alone costs British agriculture over £24 million per annum. While these are clearly infectious conditions associated with a range of bacteria, establishing the role(s) of individual organisms, and identifying the means by which they cause damage, has proved difficult.
Fusobacterium necrophorum is a versatile pathogen of both animal and human hosts and in addition to infections of the foot is associated with conditions including abscesses and respiratory infections. However, although the organism is known to produce a range of surface-associated and secreted proteins including haemolysins, leukotoxins, proteases and DNAses, the contributions of these potential virulence factors to the disease process in most cases unclear.
We hypothesise that Fusobacteriumvirulence factor expression can distinguish disease-associated bacterial strains from benign/commensal colonists. Hence we propose to study Fusobacterium sp. from clinical veterinary isolates in order to identify and characterise virulence factors expressed by these strains, with longer term the goals of establishing their roles in pathogenesis and exploiting them as targets for detection/identification of pathogenic strains in clinical samples and/or p otential treatments or vaccines. The student will use PCR and -omics-based methods to test bacteria sampled from infected livestock for known and potential virulence factors and seek to correlate these data with disease outcome. Selected strains will be evaluated in biochemical and cell-based assays and these data used to identify target proteins for biochemical and structural characterisation.
The results will provide new information on how Fusobacterium causes disease and identify potential targets for treatments to ameliorate its impact on livestock species. The student will work in a multidisciplinary environment and receive training in a range of veterinary and molecular biology methodologies.
When applying please select ’Veterinary Science’ PhD within the Faculty of Health Sciences.
References
Exploring the Role of Residue 228 in Substrate and Inhibitor Recognition by VIM Metallo-β-lactamases. Mojica MF, Mahler SG, Bethel CR, Taracila MA, Kosmopoulou M, Papp-Wallace KM, Llarrull LI, Wilson BM, Marshall SH, Wallace CJ, Villegas MV, Harris ME, Vila AJ, Spencer J, Bonomo RA. (2015) Biochemistry, 54, 3183-96.
Brem, J., van Berkel, S.S., Aik, W., Rydzik, A., Avison, M., Pettinati, I., Umland, K.-D., Kawamura, A., Spencer, J., Claridge, C., Mcdonough, M., & Christopher Schofield, C.J. (2014). Rhodanine Hydrolysis Leads to Potent Thioenolate Mediated Metallo-β-Lactamase Inhibition. Nat. Chem. 6, 1084-90
Witcomb LA, Green LE, Calvo-Bado LA, Russell CL, Smith EM, Grogono-Thomas R, Wellington EM. First study of pathogen load and localisation of ovine footrot using fluorescence in situ hybridisation (FISH) Vet Microbiol. 2015 Apr 17;176(3-4):321-7. doi: 10.1016/j.vetmic.2015.01.022.
Hill, D.J., Whittles C & Virji M (2012)A novel group of Moraxella catarrhalis UspA proteins mediates cellular adhesion via CEACAMs and vitronectin (2012). PLoS One.2012;7(9):e45452. doi: 10.1371/journal.pone.0045452.
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