EASTBIO - Genome analyses of the polymicrobial niche of bovine mastitis and characterising therapeutic bacteriophages for key bacterial species

Funding

This 4-year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership. This opportunity is open to UK and International students and provides funding to cover tuition fees at the UK rate, plus a stipend to support living costs.

The proportion of international students appointed through the EASTBIO DTP is capped at 30% by UKRI BBSRC. All students must meet the eligibility criteria as outlined in the UKRI guidance at UKRI Training Grant Terms and Conditions, esp. TGC 5.2 & Annex B. Please contact [Email Address Removed] if you are unsure of your fee status.

The Project

Bovine mastitis is a poly-bacterial disease characterised by the inflammation of the regions of the udders of dairy and beef cattle and can affect the welfare and productivity of diseased animals costing ~€26 billion annual loss to the dairy industry, globally.

The major bacterial pathogens associated with bovine mastitis are representative species from the genera Staphylococcus, Streptococcus, Enterococcus, Actinomyces, Aerococcus, Escherichia, Klebsiella and Proteus. Conventional treatment relies on antibiotics to control the pathogens in udders and prevent intramammary transmission in non-lactating cows. However, antibiotic resistance has been reported in these organisms, both in terms of individual species, and individual strains within species and there are declining antibiotic innovations to control these new phenotypes. In addition to acquisition of antibiotic resistance genes by certain organisms via modes such as transformation, conjugation and transduction, the bacterial strains can aggregate and form biofilms which protect the bacteria by impeding antibiotic efficacy. These factors clearly reduce food safety and security and increase public health concerns. Therefore, novel and effective alternative strategies to replace or supplement antibiotics for the control of bovine mastitis are needed.

Bacteriophages (phages) are viruses which infect bacteria by targeting and killing bacteria with extreme precision. Depending on the phage, this precision of infection can be at the level of the bacterial genus, species, or even strain. Although discovered over a century ago, phages are gaining more recognition lately due to increased awareness of their potential roles and they have been shown to greatly mitigate bacterial resistance and can improve the general health and production capacity of livestock. Phages are easy to isolate and develop, can effectively target and kill antimicrobial resistant strains in biofilms, are safe for use in animals and can amplify at infection sites to ensure a continuous dose supply.

For bovine mastitis, several research studies have reported the isolation, characterisation, and safety and efficacy testing of therapeutic phages in vitro, ex vivo and in vivo however, only single bacterial species were targeted in each case. Here, we aim to isolate and characterise lytic phages that would be combined as a phage cocktail to kill a range of key bacterial species causing bovine mastitis. To do this, we would take advantage of our vast bacterial isolate collection from mastitic cows in the UK and analyse their genome diversity, virulence genes, markers of evolution and antibiotics resistance profiles. The five most-dominant species would be targeted for phage isolation from raw milk, sewage and manure samples. The morphology, stability, host range, kinetics and genome content of the phages would be characterised, and suitable phage candidates would be combined into cocktails to improve bacterial host coverage, lysis, and to mitigate resistance development. The therapeutic activity of optimal cocktails would be tested in pure cultures, biofilms and Galleria mellonella, a species of moth which has been used successfully to act as a eukaryote host for infection by a range of bacterial species and subsequent infection by phages.

Knowledge gained from this approach would direct formulation of the phages to be used to ensure optimal delivery in cattle for the treatment of bovine mastitis.

Eligibility

Eligibility criteria are available on the EASTBIO how to apply webpage.

How to Apply

To apply for an EASTBIO PhD studentship, please follow the guidance on the EASTBIO how to apply webpage. EASTBIO can provide you with support for your application and details are available on the webpage.

Informal enquiries about the project and your application should be addressed to the project supervisor, Dr Neil McEwan - [Email Address Removed]

After you have approached the project supervisor and discussed your application with them, you should:

1) Download and complete the online EASTBIO Equality, Diversity and Inclusion survey; the survey will automatically generate a Unique Number that you should copy and paste on the relevant section of your EASTBIO Application Form.

2) Download and fill in the EASTBIO Application Form. You can only apply for one EASTBIO PhD project.

3) Download and send the EASTBIO Reference Form to your two academic/professional referees, and ask them to submit the references directly to [Email Address Removed] by 27 November 2023

4) Submit your complete application, along with academic transcripts and certificates to [Email Address Removed] by 27 November 2023

If you require any additional assistance in submitting your application or have any queries about the application process, please don't hesitate to contact us at [Email Address Removed]