Date of Award
Doctor of Philosophy
Dr. Aidan Coffey
This thesis describes the successful isolation and characterisation of novel phages with applications in the medical/veterinary sector and also in the food and beverage industry. This thesis begins with a comprehensive literature review on the biocontrol applications of phages which will appear as a book chapter in “Phage therapy; Current research and applications” edited by Andrzej Gorski in the Hirszfeld Institute of Immunology and Experimental therapy, Wroclaw, Poland.
Chapters 2 to 5 encompass the technical part of the thesis work, which begins with the isolation and characterization of phages of Lactobacillus and Pediococcus which cause spoilage in the brewing industry'. Genome sequencing of one of these phages revealed its unique nature and unusual genome organisation. This Pediococcus phage, clPl had no close homologues in the genomic databases. Its closest relative was a Lactobacillus plantarum phage, OJL-1, which showed some homology in 22 ORFs.
The second part of the technical work investigated phage K resistance mechanisms in the medically important pathogen S. aureus, and on this basis led to the devclopiuent of modified derivatives of this phage with broader host ranges. Combination of six of these modified derivatives into a phage mixture with the parent phage K resulted in the generation of a potent anti- staphylococcal cocktail for biocontrol applications. Subsequently, this phage mixture was exploited for the successful prevention of S. aureus biofilms and also removal of established biofilm biomass. In addition, inflammatory immune response assays using primary human umbilical vascular endothelial cells (HUVECs) indicated that stimulation of these cells with phage K did not induce expression of adhesion molecules, transcriptional activators, or cytokines suggesting a lack of an immune response to phage K in these cells.
Kelly, David, "The Exploitation of Bacteriophages for the Biocontrol of Spoilage and Pathogenic Bacteria Including MRSA" (2011). Theses [online].
Available at: https://sword.cit.ie/allthe/224