Novel bacteriophages and their derived proteins for the biocontrol of proteus and pseudomonas biofilms

Abstract

Antimicrobial resistance (AMR) is set to be the next global pandemic with AMR related deaths set to outgrow cancer deaths by the year 2050. Increasing resistance to the traditional arsenal of antibiotics is expanding at an alarming rate and novel antimicrobial therapeutics are urgently required to tackle this emerging issue. Proteus mirabilis and Pseudomonas aeruginosa are two bacterial species commonly associated with urinary tract infections in humans. To contribute to the progression of novel antimicrobials against P. mirabilis and P. aeruginosa, this thesis was based on the isolation and utilisation of bacteriophages and bacteriophage derived products to help treat biofilms caused by both bacteria. The isolation of phage PM-CJR showed promising antimicrobial potential against P. mirabilis due to the production of depolymerase enzymes. The thesis describes the identification and utilisation of both the whole phage and its tail-spike protein with the pectate lyase activity to treat P. mirabilis biofilms. The phage and the tail-spike protein were assessed in a range of different in vivo and in vitro assays to demonstrate their antimicrobial and antivirulence properties against P. mirabilis biofilms. This thesis also studies the combinational treatment of phage and cold atmospheric plasma for the treatment of P. aeruginosa biofilms and establishes the most effective order or application of each antimicrobial for the most effective treatment option against P. aeruginosa biofilms. We successfully showed that the use of CAP followed by exposure to P. aeruginosa phages is the most effective order of application for eradication of P. aeruginosa biofilms.

Date of Award	Dec 2022
Original language	English
Awarding Institution	Queen's University Belfast
Supervisor	Brendan Gilmore (Supervisor), Tim Skvortsov (Supervisor) & Christopher C R Allen (Supervisor)