A Porcine Model for Urinary Tract Infection

Abstract

Urinary tract infection (UTI) is the most common bacterial infectious disease with a high frequency of recurrence and the leading cause of septicemia. In vivo experimentation has contributed significantly to the present-day knowledge on UTI pathogenesis. This research has traditionally been based on murine models of UTI. Occasional conflicting results between UTI in mice and humans and increasing skepticism toward small rodent models in general warrant the need of novel large-animal infection models that better resemble the anatomy and physiology of humans, and thus better mimic the course of infection in humans. Here, we report, to our knowledge, the first large-animal model of cystitis. The model is based on pigs, and the protocol supports the establishment of persistent, non-ascending infection in this animal and is established without invasive surgical procedures, pain, and discomfort for the animal. The course of infection is monitored by cystoscopy, microscopy of bladder biopsies, and biochemical analysis of urine and blood samples. At termination, harvested whole bladders from infected pigs are analyzed for microbiological colonization using microscopy, histology, and viable bacterial counts. The model is a useful tool in future studies of UTI pathogenesis and opens up novel possibilities to bridge the current knowledge obtained from small-animal UTI models to UTI pathogenesis in humans.

Self‐Limiting Mussel Inspired Thin Antifouling Coating with Broad‐Spectrum Resistance to Biofilm Formation to Prevent Catheter‐Associated Infection in Mouse and Porcine Models

“…To validate the efficacy of our coating in a relevant large‐animal model, we chose to use a porcine catheter‐associated urinary tract infection (CAUTI) model ( Figure A) due to the fact that the porcine urinary tract most closely resembles that of the human both genetically and anatomically and is the accepted large‐animal model for testing of urinary devices. [ 33 ] Furthermore, for these studies we chose to use uropathogenic E. coli , as it is the most common cause for UTI, [ 34 ] causing 70–95% upper and lower UTIs. [ 35 ] For this, both a coated and uncoated catheter were tested in each animal (one after the other in two separate rounds with infection verified via CFU counts on day of exchange), with the urinary tract infection induced via instillation of 10 7 CFU into the bladder on day 1 (Figure 10A).…”

Recurrent Urinary Tract Infection: A Mystery in Search of Better Model Systems

“…To our knowledge, only one group has studied human biopsies and reported the existence of IBC and QIR (De Nisco et al, 2019). In contrast, in a recent study with a porcine model, which has a more similar urogenital anatomy, physiology and immune response to human compared with small-animal models, IBCs were not observed in the bladder after UPEC infection, although high loads of bacteria were detected after prolonged infection, some forming biofilm-like extracellular aggregates (Nielsen et al, 2019). Therefore, more studies on the role of IBC and QIR in rUTI in humans or human bladder model systems would be welcome.…”

Perspective: Humanized Pig Models of Bladder Cancer

“…The porcine urological system is similar anatomically and physiologically to humans. A porcine model of cystitis (inflammation of the bladder) has been developed due to the pig's urothelial similarities to humans' (Nielsen et al, 2019), and regular cystitis is positively associated with BC risk (Vermeulen et al, 2015).…”