Date of Award

2024

Document Type

Doctoral Thesis

Degree Name

Doctor of Philosophy

Department

Biological Sciences

First Advisor

Dr. Eamonn Culligan

Second Advisor

Prof Roy Sleator

Third Advisor

Dr Craig Murphy

Abstract

Urobiome research is currently at a nascent stage, due to a previously incorrect assumption that the bladder is a sterile environment. Improvements in bacterial culturing and DNA sequencing techniques have revealed a diverse resident bacterial community within the urinary tract (urobiome). As global incidences of multidrug- resistant urinary tract infections (UTIs) continue to increase, so too does the demand for novel antimicrobial therapies. Due to its relatively understudied nature, the urobiome represents a reservoir that could be mined as a potential source of novel antimicrobial compounds (e.g., bacteriocins). The aim of this thesis was to identify urobiome bacteriocins that could potentially be used as alternative treatment strategies for antibiotic resistant UTIs, specifically those caused by uropathogenic Escherichia coli (UPEC). An in-silico screen of 181 previously identified urobiome isolates resulted in the discovery of 53 novel bacteriocin variants. Additionally, using a combination of in vitro and in silico approaches, screening of human urine samples identified numerous urinary isolates with antimicrobial activity against clinical UPEC strains. The combined approach of in vitro and in silico screening highlights the overall bacteriocin production potential of the urobiome, which until now, remained relatively understudied. This thesis presents a previously unmined microbiome for its antimicrobial peptides, with a specific focus on bacteriocins with activity against UPEC.

Creative Commons License

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

Access Level

info:eu-repo/semantics/openAccess

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