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Updated: Aug 1, 2025
Establishment and Characterization of UTI and CAUTI in a Mouse Model
Published on: June 23, 2015
Development of a High-Throughput Urosepsis Mouse Model
Roman Herout1,2, Sreeparna Vappala3,4, Sarah Hanstock1
1The Stone Centre at Vancouver General Hospital, Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.
Abstract:
Murine sepsis models are typically polymicrobial, and are associated with high mortality. We aimed to develop a high-throughput murine model that mimics a slow-paced, monomicrobial sepsis originating from the urinary tract. A total of 23 male C57Bl/6 mice underwent percutaneous insertion of a 4 mm catheter into the bladder using an ultrasound-guided method, previously developed by our group. The following day, Proteus mirabilis (PM) was introduced percutaneously in the bladder in three groups: g1-50 µL 1 × 108 CFU/mL solution (n = 10); g2-50 µL 1 × 107 CFU/mL solution (n = 10); and g3 (sham mice)-50 µL sterile saline (n = 3). On day 4, mice were sacrificed. The number of planktonic bacteria in urine, adherent to catheters, and adherent to/invaded into the bladder and spleen was assessed. Cell-free DNA, D-dimer, thrombin-antithrombin complex (TAT), and 32 pro-/anti-inflammatory cytokines/chemokines were quantified in the blood. All mice survived the 4 day postinterventional period. Mean weight loss was 11% in g1, 9% in g2, and 3% in the control mice. Mean urine CFU counts were highest in group 1. All catheters showed high catheter-adhered bacterial counts. Of the infected mice, 17/20 had CFU counts in the splenic tissue, indicating septicemia. Plasma levels of cell-free DNA, D-dimer, and the proinflammatory cytokines IFN-γ, IL-6, IP-10, MIG, and G-CSF were significantly elevated in infected mice versus controls. We present a reproducible, monomicrobial murine model of urosepsis that does not lead to rapid deterioration and death, and is useful for studying prolonged urosepsis.
Insights
Researchers developed a new murine model for studying urinary tract infections (UTIs) and sepsis. This model uses a single bacterium, Proteus mirabilis, to mimic slow-progressing urosepsis without high mortality, aiding research into prolonged infections.
Area of Science:
- Microbiology
- Immunology
- Urology
Background:
- Murine sepsis models are often polymicrobial and associated with high mortality.
- A need exists for models that mimic slow-paced, monomicrobial sepsis, particularly originating from the urinary tract.
Purpose of the Study:
- To develop a high-throughput murine model for studying monomicrobial urosepsis.
- To create a model that mimics a slow-paced infection without rapid mortality, allowing for the study of prolonged sepsis.
Main Methods:
- Ultrasound-guided percutaneous bladder catheterization in C57Bl/6 mice.
- Introduction of Proteus mirabilis (PM) into the bladder to establish monomicrobial urosepsis.
- Assessment of bacterial load, cell-free DNA, D-dimer, and cytokine/chemokine profiles in blood and tissues.
Main Results:
- All mice survived the 4-day study period, indicating a non-lethal model.
- Significant increases in plasma cell-free DNA, D-dimer, and pro-inflammatory cytokines (IFN-γ, IL-6, IP-10, MIG, G-CSF) were observed in infected mice.
- High bacterial loads were found in urine, on catheters, and in splenic tissue, confirming septicemia.
Conclusions:
- A reproducible, monomicrobial murine model of urosepsis was successfully developed.
- This model does not cause rapid deterioration or death, making it suitable for studying prolonged urosepsis.
- The model allows for investigation of host responses, including inflammation and coagulation, during sustained urosepsis.
