Author: Rushita Jivanbhai Savaliya
Savaliya, Rushita Jivanbhai, 2025 Impact of Increased Urothelial Permeability on Acute Urinary Tract Infection Severity and Persistence, Flinders University, College of Medicine and Public Health
Terms of Use: This electronic version is (or will be) made publicly available by Flinders University in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. You may use this material for uses permitted under the Copyright Act 1968. If you are the owner of any included third party copyright material and/or you believe that any material has been made available without permission of the copyright owner please contact copyright@flinders.edu.au with the details.
Urinary tract infection (UTIs) is one of the most common infections, with a 50-60% occurrence in lifetime. The urothelial glycosaminoglycan (GAG) layer is an essential component of bladder defense, maintaining barrier integrity. The GAG layer of the epithelium bladder functions as a barrier against pathogens and bacterial attachment. Clinical studies demonstrated that damage to the GAG layer may enhance susceptibility to infection, and infection increases in the bladder. This study aimed to explore that if damage to the GAG layer increases urothelial permeability and susceptibility to UTI infection caused by UPEC in a murine model. Uropathogenic Escherichia coli strain ATCC CFT073 was used to assess the defensive function of the GAG layer. Female C57BL/6J mice were catheterized transurethral and treated with Protamine sulphate (PS), a polycationic compound known to degrade the GAG layer and increase urothelial permeability, and Phosphate Buffered Saline(PBS) served as control. PS-treated mice showed high bacterial load in urine (1.6 x 107) at 24 hours post-infection, and gradually it decreased with time (over 72 hours), implying partial recovery of bladder defense, while PBS-treated mice( 1.6 x 108) had stable and consistent bacterial clearance. In PS-treated mice, quantifiable bacterial colonization was detected in kidneys 1 x 103 CFU/kidneys, whereas no bacteria were detected in the kidneys or spleen of PBS-treated controls. The absence of bacteria in the spleen in both groups confirms infection was localized to the urinary tract. Finding support for the hypothesis and GAG acts as a first line of defense and maintains its barrier integrity. Disruption of the GAG layer significantly increases urothelial permeability and susceptibility to urinary tract infection, as evidenced by higher urinary bacterial load in GAG-depleted mice compared to controls. The findings confirm that the GAG layer serves as a critical barrier against uropathogenic Escherichia coli colonization and local infection. Moreover, it also highlights GAG replenishment therapies to prevent recurrent UTIs. Future studies should evaluate the efficacy of GAG replenishment therapies in preventing recurrent UTIs with the treatment of antibiotics.
Keywords: Keywords: Urinary tract infection, Uropathogenic Escherichia coli (UPEC), Glycosaminoglycan, Protamine sulphate, Phosphate buffered saline, infection, rUTI.
Subject: Biotechnology thesis
Thesis type: Masters
Completed: 2025
School: College of Medicine and Public Health
Supervisor: Dr. Luke Grundy