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Thesis Format

Integrated Article

Degree

Master of Science

Program

Microbiology and Immunology

Supervisor

Burton, Jeremy

Abstract

Urgency urinary incontinence is a common symptom of overactive bladder (OAB) and urinary tract infection (UTI), which can be triggered by extracellular adenosine triphosphate (eATP) through purinergic signaling. Current treatments for OAB and UTI fail to consider the potential impact of eATP. It is hypothesizes that certain commensal Lactobacillus spp. can modulate levels of eATP released by pathogenic bacteria. This project examined bacterial modulation of eATP during growth, the impact of prebiotics on lactobacilli growth, and studied its reduction in an in vitro bladder infection model. Release and uptake of ATP by a range of commensal and pathogenic bacteria was observed. Lactobacillus crispatus ATCC 33820 and Lactobacillus gasseri KC-1 able to reduce supplemented and E. coli IA2-derived ATP, was enhanced in culture with select prebiotics. This research builds a greater understanding of the handling of eATP by bacteria and suggests a prebiotic-probiotic application that could potentially improve bladder health.

Summary for Lay Audience

A urinary tract infection (UTI) can occur in any part of the urinary system (kidneys, ureter, bladder, or urethra). Not all UTIs have symptoms, but common ones are frequent urination, pain, or burning with urination. Uropathogenic Escherichia coli frequently cause this condition. Overactive bladder (OAB) is a collection of symptoms where one feels a frequent and urgent need to urinate regardless of bladder volume and consequently may experience urinary incontinence. Urgency urinary incontinence is the sensation to urinate regardless of bladder volume, a symptom of both conditions. It is now becoming apparent that UTI and OAB are somewhat associated with disruption of the normal commensal bacteria, the microbiota. Each individual has a diverse microbiota containing trillions of microbes that are compositionally different based on their location. For example, a healthy urogenital system (urinary tract and genital tract) has a microbiota dominated by Lactobacillus species.

Commensal and pathogenic bacteria release adenosine triphosphate (ATP) into the environment while they grow. All living things utilize ATP, which is a universal energy molecule and is used to power cellular functions. Studies have shown that it is an important signaling molecule for cell and host nervous systems. The release of ATP during growth allows a bacterium to communicate with the host, influence the environment, and be taken up later as an additional nutrient source. Several urinary-associated microbes and pathogenic E. coli can release relatively large amounts of ATP, which may trigger the host nervous system and potentially contribute to the feeling of urgency associated with UTIs and OAB. However, some commensal lactobacilli take up ATP during growth or produce substances that could reduce the adverse effects of ATP on the bladder. These lactobacilli can potentially be administered as probiotics (live microorganisms that, when administered in adequate amounts, confer a health benefit on the host) to reduce urinary ATP. Probiotics can be supported, or beneficial indigenous strains promoted, by prebiotics. Prebiotics are substrates selectively utilized by microorganisms conferring a health benefit. The use of lactobacilli and prebiotics to address abundant urinary ATP was a previously unexplored and promising method for urgency symptom management.

Creative Commons License

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

Available for download on Thursday, September 01, 2022

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