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Updated: Jan 12, 2026
An In Vitro Bladder Model of Catheter-Associated Urinary Tract Infection
Published on: June 24, 2025
Harnessing microbial-derived metabolites in the urinary tract to prevent infection induced catheter encrustation
L Beryl Guterman1, Madalyn Motsay1, Benjamin C Hunt1
1Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
Abstract:
Proteus mirabilis is a predominant cause of catheter associated urinary tract infection (CAUTI), and a key virulence factor is its urease enzyme which can increase urine pH and form urinary stones, causing catheter blockage and facilitating bacteremia. The only FDA approved urease inhibitor, acetohydroxamic acid (AHA), has side effects that limit its clinical use, necessitating new approaches to target urease activity. We previously discovered that common urinary tract colonizers modulate P. mirabilis urease activity via secreted small molecules. In this study, we conduct a metabolomics analysis of six modulatory bacterial species to reveal urease-dampening metabolites. Of 31 candidate metabolites, seven reproducibly decrease P. mirabilis urease activity. All seven metabolites dampen urease activity in other urease-positive bacterial species, suggesting conserved targets. Six of the metabolites act via mixed inhibition of the urease enzyme. One metabolite, D-imidazole lactate, exhibits a non-competitive mechanism of urease inhibition along with antimicrobial activity and repression of the urease operon in P. mirabilis. Metabolite combinations with AHA demonstrate synergistic activity and prevent catheter encrustation in an in vitro model for CAUTI. Prophylactic use of urease dampening metabolites with AHA could improve the efficacy of antimicrobial treatment against catheter biofilms.
Insights
Researchers identified seven metabolites that reduce Proteus mirabilis urease activity, a key factor in catheter-associated urinary tract infections (CAUTIs). These compounds, particularly D-imidazole lactate, show promise in preventing catheter blockage and biofilms when combined with existing treatments.
Area of Science:
- Microbiology
- Biochemistry
- Infectious Diseases
Background:
- Proteus mirabilis is a major cause of catheter-associated urinary tract infections (CAUTIs).
- Its urease enzyme increases urine pH, leading to stone formation, catheter blockage, and bacteremia.
- Current urease inhibitor acetohydroxamic acid (AHA) has limited clinical use due to side effects.
Purpose of the Study:
- To identify novel urease-dampening metabolites produced by urinary tract bacteria.
- To investigate the mechanisms of urease inhibition by these metabolites.
- To evaluate the potential of these metabolites in preventing CAUTI.
Main Methods:
- Metabolomics analysis of six bacterial species known to modulate P. mirabilis urease.
- In vitro assays to test the effect of candidate metabolites on P. mirabilis urease activity.
- Enzyme kinetics studies to determine inhibition mechanisms.
- In vitro CAUTI model to assess metabolite efficacy in preventing catheter encrustation.
Main Results:
- Seven out of 31 candidate metabolites reproducibly decreased P. mirabilis urease activity.
- All seven metabolites showed inhibitory effects on other urease-positive bacteria, indicating conserved targets.
- Six metabolites acted via mixed inhibition; D-imidazole lactate exhibited non-competitive inhibition, antimicrobial activity, and repressed the urease operon.
- Combinations of metabolites with AHA showed synergistic effects and prevented catheter encrustation in vitro.
Conclusions:
- Novel urease-dampening metabolites were identified with potential for CAUTI prevention.
- D-imidazole lactate demonstrates a multi-faceted inhibitory mechanism.
- Combining these metabolites with AHA offers a promising strategy to enhance CAUTI treatment and prevent catheter biofilms.
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