Investigation of phage therapy approaches as attractive alternative to antibiotics for bio-control of genitourinary infections

Several case studies have demonstrated phage effectiveness against UTIs. To explore alternative treatments for P. mirabilis-caused CAUTIs, environmental samples from Northern Ireland were collected, leading to the isolation of phage AS1 from composted cow dung. Phage AS1 exhibited lytic activity, robust stability across pH, temperature, and chloroform exposure, rapid host adsorption, a good burst size, and a narrow host range.

Genomic analysis identified no lysogeny-associated genes and confirmed lytic gene cassettes. Phage AS1 significantly reduced P. mirabilis biofilm load and biomass. Additionally, cold atmospheric plasma (CAP) treatment was used to prepare a phage-immobilised antibacterial silicone surface.

CAP-modified silicone enhanced phage attachment by altering surface properties. Immobilised phages remained active and prevented P. mirabilis migration across catheter segments. Plasma-activated water (PAW) produced by Spark and Glow discharge was characterised.

Spark 30 PAW showed superior antibacterial activity and, combined with phage, achieved a 4-log reduction in bacterial load and 97% biofilm biomass reduction, even in artificial urine. Finally, novel Proteus phage endolysins LysPM1 and LysPM2 were identified, showing stability and strong antibacterial activity with outer membrane permeabilisers. Overall, this thesis supports phage-based strategies for preventing and treating Proteus-associated CAUTIs.<br><br><i>Thesis is embargoed until 31 July 2028.</i>