Development of a High-Throughput Urosepsis Mouse Model

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Roman Herout - , Klinik und Poliklinik für Urologie, University of British Columbia (Autor:in)
  • Sreeparna Vappala - , University of British Columbia (Autor:in)
  • Sarah Hanstock - , University of British Columbia (Autor:in)
  • Igor Moskalev - , University of British Columbia (Autor:in)
  • Ben H. Chew - , University of British Columbia (Autor:in)
  • Jayachandran N. Kizhakkedathu - , University of British Columbia (Autor:in)
  • Dirk Lange - , University of British Columbia (Autor:in)

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

OriginalspracheEnglisch
Aufsatznummer604
Seitenumfang12
FachzeitschriftPathogens
Jahrgang12 (2023)
Ausgabenummer4
PublikationsstatusVeröffentlicht - 15 Apr. 2023
Peer-Review-StatusJa

Schlagworte

Ziele für nachhaltige Entwicklung

Schlagwörter

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

Bibliotheksschlagworte