About the Project
Salmonella enterica, a food-borne pathogen classified as a WHO priority pathogen, is in urgent need of new therapeutic approaches as it becomes increasingly antibiotic resistant. One potential solution is phage therapy, where viruses that kill bacteria are used as a treatment. However, a major challenge is that different Salmonella serovars can cause similar clinical syndromes, while phages are often serovar-specific. While broad-range phages that target not only Salmonella but also Escherichia coli do exist (Fong et al. 2021), we are only beginning to understand the factors that determine host range. For example, an acetyl esterase domain appears to be necessary for phages to target the Vi capsule of Salmonella Typhi (Pickard et al. 2010).
This project aims to better understand the features that determine phage specificity towards different Salmonella serovars and, in doing so, investigate approaches for developing therapeutic phages with broader host ranges. The project will also explore the potential for phages to target intracellular Salmonella infection.
In this project, the student will:
- Isolate and sequence novel phages targeting different Salmonella serovars
- Test the host range of these phages against different serovars, strains and E. coli to understand which receptors the phages target
- Carry out a pangenome-wide association analysis to identify phage features, such as tail fibre proteins, that determine receptor specificity
- Investigate whether these can be modified to generate phages capable of targeting multiple strains or serovars
- Explore phage activity against intracellular Salmonella using human cell lines
