Date of Award


Document Type

Doctoral Thesis

Degree Name

Doctor of Philosophy


Biological Sciences

First Advisor

Prof Aidan Coffey


Bacterial resistance to conventional antibiotics has become an urgent healthcare issue worldwide. In this light, a renewed interest has emerged for therapy with bacteriophages (phages), which are viruses that can specifically infect bacteria. These viruses encode different proteins that degrade specific bonds within the bacterial cell wall, both to inject their genomic material into the bacterial cells and to release the viral progeny: virion-associated hydrolases and endolysins, respectively. Elimination of Gram-positive pathogens with recombinant versions of phage enzymes represents a promising alternative to classical antibiotics. In this thesis, different phage therapy strategies involving either whole phages or the use of recombinant versions of endolysins are developed against different Gram-positive bacteria. Firstly, two novel phages targeting Staphylococcus aureus were isolated from a therapeutic cocktail and some phage Open Reading Frames with unknown function were studied for their implications in bacterial host range. Genomic analysis of the Irish MRSA collection was carried out to understand their different susceptibilities to different phages. An engineered staphylococcal endolysin was developed with enhanced antibiofilm activity. Other Gram-positive pathogens such as Gardnerella vaginalis and Clostridium difficile were also subject of study in this thesis, and novel endolysins targeting them were obtained and characterized.

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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