Bacteriophage (phage) are viruses that specifically infect and kill bacterial cells, making phage therapy an exciting option to treat bacterial infections. With the growing threat of antibiotic resistance, there is considerable commercial and academic investment in phage therapy but hurdles still exist to its successful application in both humans and animals. There has been incredible progress in understanding how bacteria resist phage predation under laboratory conditions, but how important these processes are during actual infections is unknown. This knowledge is critical to selection of phage in therapeutic cocktails that can work together to counter these bacterial defence systems. Our grouping has worked on the pathogenesis of Escherichia coli for over twenty years, understanding how specific strains cause different types of infection and we are now applying this knowledge to development of phage therapy which requires studying the interaction of phages with their target bacteria in the host during infection. As with antibiotics, bacterial resistance to phage also occurs and while this is relatively well characterised under laboratory conditions, it is less understood in the host where the fitness costs of bacterial resistance are critical. Ideally phage will work in synergy with the host response to eradicate the infection and this complexity requires an infection model. We are developing a pig model of urinary tract infection for phage therapy development as there is colonisation of a complex epithelium that can be accessed for phage delivery. We will focus on Escherichia coli infections with our commercial partner, Proteon Pharmaceuticals, who bring a wealth of expertise in phage therapy development to the research. The project will fully characterise the dynamics of the infection following phage delivery including dissemination of phage and co-ordination with the inflammatory response. The major focus will be on bacterial resistance to the phage treatment which will be investigated by sequencing isolates and studying their gene expression profile by RNAseq. The results will be compared with data acquired on resistance mechanisms for the same strains under laboratory conditions. The results from this project should improve selection of phage for cocktails for treatment of multiple bacterial infections such as mastitis/metritis in cattle or APEC infections in poultry. This project will benefit from world class facilities on campus including the Large Animal Research and Imaging Facility (LARIF) and the knowledge and resources provided by Proteon Pharmaceuticals, which has a platform to develop and commercialize phage-based products for animal and human health.
This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership (DTP) http://www.eastscotbiodtp.ac.uk/how-apply-0 .
EASTBIO Application and Reference Forms can be downloaded via http://www.eastscotbiodtp.ac.uk/how-apply-0
Please send your completed EASTBIO Application Form along with a copy of your academic transcripts to [Email Address Removed]
You should also ensure that two references have been send to [Email Address Removed] by the deadline using the EASTBIO Reference Form.
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