Author ORCID Identifier

0000-0002-3960-9636

Date of Graduation

5-2026

Document Type

Dissertation (PhD)

Program Affiliation

Microbiology and Infectious Diseases

Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Jennifer Walker, PhD

Committee Member

Blake Hanson, PhD

Committee Member

Anna Konovalova, PhD

Committee Member

Michael Lorenz, PhD

Committee Member

Bhanu Priya Ganesh, PhD

Abstract

Catheter-associated urinary tract infections (CAUTI) are the most common hospital associated infection, with over 1 million cases in the United States alone. While uncomplicated urinary tract infections are predominantly caused by Escherichia coli, CAUTI are caused by a wide range of uropathogens, many of which are understudied. One such pathogen, Staphylococcus aureus is particularly problematic, as it is often multidrug resistant, is associated with more severe infection, and is a frequent cause of urinary catheter blockages. Contributing to these catheter blockages is the enzyme urease. Urease is a nickel dependent metalloenzyme that hydrolyzes urea into ammonia and carbon dioxide. The production of these byproducts causes alkalization, which causes the precipitation of various ions in the urine, including calcium and magnesium. These precipitates can encrust the surface of the catheter and contribute to blockages, which result in device failure and ultimately decreased quality of life for the catheterized individual. While urease is well-understood in another uropathogen, Proteus mirabilis, the role of urease during S. aureus CAUTI and the regulation of the enzyme are still under investigation. In this dissertation, I determined that urease is important for biofilm formation in conditions that mimic the catheterized bladder environment. Furthermore, I found that urease was essential for dissemination from the bladder to the kidneys during early stages of CAUTI.  My analysis of the regulatory pathway of urease reveled three novel regulators of urease – SigB, SrrA, and SaeR. Furthermore, I showed the environmental conditions that mimic the urinary tract are important for urease expression. Lastly, I utilized whole genome sequencing of urinary catheter-associated isolates to identify SNPs that contribute to urease expression and activity. This work provides insights on the virulence and molecular regulation of urease in the urinary tract in a widely understudied uropathogen. Furthermore, this work can be expanded on to provide insights on novel therapeutics that can target urease to treat S. aureus CAUTI.

Keywords

microbiology, bacterial pathogens, CAUTI, Staphylococcus aureus, gene regulation, urease

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