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.
Highlights
Urinary tract infections (UTIs) are the most common bacterial infection with an annual incidence of community-acquired UTIs of more than 10% for women in the United States (Foxman, 2014)
Given that UTI remains a considerable challenge at hospitals and in the community, it is critical that the considerable fundamental biological investigation conducted over the past decades is translated into actual novel treatment regimens
A key step to achieve this is the verification that previous results obtained from in vitro and small-animal models reflect the infection pathogenesis in humans
Summary
Urinary tract infections (UTIs) are the most common bacterial infection with an annual incidence of community-acquired UTIs of more than 10% for women in the United States (Foxman, 2014). This high incidence is partly explained by the prevalent frequency of recurrent infections following approximately 25–40% of acute UTIs and bringing about severe morbidity in otherwise healthy women (Foxmann, 2010). Improved hygiene procedures and antibiotic stewardship are important steps to control UTIs (Cai et al, 2016). A better fundamental understanding of UTI pathogenesis is critical to improve treatment regimens and develop more targeted antimicrobials
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