Development of a High-Throughput Urosepsis Mouse Model

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Roman Herout - , Department of Urology, University of British Columbia (Author)
  • Sreeparna Vappala - , University of British Columbia (Author)
  • Sarah Hanstock - , University of British Columbia (Author)
  • Igor Moskalev - , University of British Columbia (Author)
  • Ben H. Chew - , University of British Columbia (Author)
  • Jayachandran N. Kizhakkedathu - , University of British Columbia (Author)
  • Dirk Lange - , University of British Columbia (Author)

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.

Details

Original languageEnglish
Article number604
Number of pages12
JournalPathogens
Volume12 (2023)
Issue number4
Publication statusPublished - 15 Apr 2023
Peer-reviewedYes

Keywords

Sustainable Development Goals

Keywords

  • catheter-associated urinary tract infection, mouse model, urosepsis

Library keywords