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An In Vitro Bladder Model of Catheter-Associated Urinary Tract Infection
Published on: June 24, 2025
Vaccination to Protect Against Proteus mirabilis Challenge Utilizing the Ascending Model of Urinary Tract Infection
Sara N Smith1, Stephanie D Himpsl2, Harry L T Mobley2
1Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA. sarazak@umich.edu.
Abstract:
Proteus mirabilis is a major cause of complicated urinary tract infections (UTIs). P. mirabilis' urease activity hydrolyzes urea and raises urine pH levels, which can catalyze bladder and kidney stone formation. This urolithiasis leads to harder-to-treat infections, possible urinary blockage, and subsequent septicemia. Development of a mucosal vaccine against P. mirabilis urinary tract infections is critical to protect against this potentially deadly infection process. Here, we describe the methodology necessary to produce a vaccine candidate conjugated to cholera toxin, administer the vaccine via the intranasal route, and test efficacy in a murine transurethral P. mirabilis infection model.
Insights
Developing a mucosal vaccine against Proteus mirabilis is crucial for treating complicated urinary tract infections (UTIs). This study outlines methods for a novel vaccine candidate and its efficacy testing in mice.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Proteus mirabilis causes complicated urinary tract infections (UTIs).
- Urease activity of P. mirabilis raises urine pH, leading to stone formation (urolithiasis).
- Urolithiasis complicates UTIs, causing blockages, sepsis, and treatment resistance.
Purpose of the Study:
- To develop a mucosal vaccine against P. mirabilis UTIs.
- To conjugate a P. mirabilis antigen to cholera toxin for enhanced immunogenicity.
- To evaluate intranasal vaccine administration and efficacy in a murine model.
Main Methods:
- Production of a vaccine candidate using P. mirabilis components conjugated to cholera toxin.
- Intranasal administration of the vaccine in a murine model.
- Testing vaccine efficacy in a transurethral P. mirabilis infection model.
Main Results:
- Methodology for producing the P. mirabilis-cholera toxin conjugate vaccine is described.
- Intranasal delivery and efficacy testing protocols are established.
- The study provides a framework for evaluating mucosal vaccine candidates against P. mirabilis.
Conclusions:
- A mucosal vaccine strategy is critical for combating P. mirabilis UTIs.
- The described methodology facilitates the development and testing of novel vaccine candidates.
- This research paves the way for effective prevention of P. mirabilis-associated urolithiasis and septicemia.
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Urinary Tract Infection I: Introduction
Urinary Tract Infection II: Pathophysiology
Urinary Tract Infection IV: Nursing Management
Urinary Tract Infection III: Diagnostic Studies and Interprofessional Care
Urinary Tract Calculi I: Introduction
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