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Updated: May 2, 2026

Establishment and Characterization of UTI and CAUTI in a Mouse Model
Published on: June 23, 2015
Copper affects virulence and diverse phenotypes of uropathogenic Proteus mirabilis
Wei-Syuan Huang1, Yuan-Ju Lee2, Lu Wang1
1Department and Graduate Institute of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Background:
Copper plays a role in urinary tract infection (UTI) and urinary copper content is increased during Proteus mirabilis UTI. We therefore investigated the effect of copper on uropathogenic P. mirabilis and the underlying mechanisms, focusing on the virulence associated aspects.
Methods:
Mouse colonization, swarming/swimming assays, measurement of cell length, flagellin level and urease activity, adhesion/invasion assay, biofilm formation, killing by macrophages, oxidative stress susceptibility, OMPs analysis, determination of MICs and persister cell formation, RT-PCR and transcriptional reporter assay were performed.
Results:
We found that copper-supplemented mice were more resistant to be colonized in the urinary tract, together with decreased swarming/swimming, ureases activity, expression of type VI secretion system and adhesion/invasion to urothelial cells and increased killing by macrophages of P. mirabilis at a sublethal copper level. However, bacterial biofilm formation and resistance to oxidative stress were enhanced under the same copper level. Of note, the presence of copper led to increased ciprofloxacin MIC and more persister cell formation against ampicillin. In addition, the presence of copper altered the outer membrane protein profile and triggered expression of RcsB response regulator. For the first time, we unveiled the pleiotropic effects of copper on uropathogenic P. mirabilis, especially for induction of bacterial two-component signaling system regulating fitness and virulence.
Conclusion:
The finding of copper-mediated virulence and fitness reinforced the importance of copper for prevention and therapeutic interventions against P. mirabilis infections. As such, this study could facilitate the copper-based strategies against UTI by P. mirabilis.
Insights
Copper impacts urinary tract infections (UTIs) caused by Proteus mirabilis. This study reveals copper
Area of Science:
- Microbiology
- Infectious Diseases
- Bacterial Pathogenesis
Background:
- Urinary tract infections (UTIs) are common, with Proteus mirabilis being a significant pathogen.
- Urinary copper levels increase during P. mirabilis UTIs, suggesting a role for copper in infection dynamics.
Purpose of the Study:
- To investigate the effects of copper on uropathogenic P. mirabilis.
- To elucidate the mechanisms by which copper influences bacterial virulence and fitness.
Main Methods:
- In vivo mouse colonization models and in vitro assays were employed.
- Methods included swarming/swimming, urease activity, adhesion/invasion, biofilm formation, and macrophage killing assays.
- Gene expression, outer membrane protein analysis, and antimicrobial susceptibility testing were also performed.
Main Results:
- Sublethal copper levels reduced P. mirabilis colonization, swarming, urease activity, and adhesion, while increasing macrophage susceptibility.
- Conversely, copper enhanced biofilm formation and oxidative stress resistance.
- Copper increased antibiotic minimum inhibitory concentrations (MICs) and persister cell formation, and modulated outer membrane proteins and RcsB expression.
Conclusions:
- Copper exhibits pleiotropic effects on P. mirabilis, influencing both virulence and fitness.
- Copper-mediated changes in bacterial behavior highlight its importance in P. mirabilis pathogenesis.
- Findings support the development of copper-based strategies for preventing and treating P. mirabilis UTIs.
Related Concept Videos
Urinary Tract Infection I: Introduction
Urinary Tract Infection II: Pathophysiology
Urine Studies II: Urine Culture and Sensitivity Test
Microbiota of the Urogenital Tract
Atypical Pneumonia
Bacterial Gastroenteritis

