This study is the first of its kind to assess the impact of indwelling bladder catheters on the colonization capability of asymptomatic Escherichia coli (E.coli) and evaluate the protective efficacy of such colonization against experimental urinary tract infections (UTI) with uropathogenic E.coli (UPEC) using a pig model.

The study uses a well-studied asymptomatic bacteriuria strain 83972, known for its adaptation to human urine and competitive advantage over UPEC in vitro, and insights from previous porcine UTI models (1, 2). Female domestic pigs (n=22), aged 13-14 weeks, with or without indwelling bladder catheters, were inoculated with 83972 followed by challenge with the symptomatic UPEC UTI isolate, UTI89.  Urine and blood samples were collected regularly, and bladders and kidneys were harvested at termination for patho-morphological evaluation. Statistics were performed using GraphPad Prism v. 9.3.1.

The results showed that colonization by the asymptomatic bacteriuria strain 83972 occurred in all pigs with indwelling catheters following inoculation, compared to only one out of eight pigs without catheters. When removing the catheter, 83972 was spontaneously cleared. Colonization with 83972 prevented experimental infection in 50% of the pigs (4 of 8) compared to controls (mock colonized with saline), all of which became infected (n=6, p=0.08). Significant colony counts of 83972 were recovered from the catheter tip and shaft demonstrating its excellent ability to colonize a foreign body in the bladder. The 83972 was isolated from the bladder of only one pig and never from the kidneys. The 83972-colonized pigs that resisted infection exhibited significantly less bladder inflammation compared to controls (P<0.0001) and infected pigs of the intervention group (P<0.0002).

This study introduces the pig as a model animal for competition studies with an ABU strain, demonstrating that 83972 cannot colonize the bladders of healthy pigs but effectively colonizes bladders (100%) in the presence of an indwelling catheter. Catheter-promoted colonization with 83972 conferred protection against experimental UTI in 50% of the pigs.
Foreign body colonization is likely the main reason for achieving a successful colonization. However, the presence of an indwelling catheter may predispose to a small amount of residual urine that could be a contributing factor to bacterial persistence. Challenges persist in maintaining long-term colonization, partly due to the spontaneous clearance post-catheter removal and limited colonization in pigs with spontaneous voiding. Continuous colonization regimens with repetitive inoculations and the use of 83972 mutants potentiated in adhesive pili have been some approaches to achieving long-term colonization in other studies, warranting further investigations. 
This study suggests that uncompromised bladder function is an obstacle to effective colonization with 83972 and may explain why human studies have struggled with low colonization rates or only focused on patients with dysfunctional voiding. In previous trials, it was possible to colonize clean intermittent catheter users, suggesting that not only patients with an indwelling catheter will be able to benefit from 83972 colonization in the long term (3). Further studies need to determine whether 83972 will have equally good colonization rates in other patient groups with different kinds of compromised bladder function. 
The study identified a UTI-protection rate in 83972 colonized pigs of 50%, which is congruent with clinical studies reporting a protection rate of 50-60% in colonized patients (3). This emphasizes the translatability of results from pigs to humans and suggests the usability of colonization in selected patients to avoid persistent and long-term antibiotic treatment.

The presence of indwelling bladder catheters strongly facilitates the asymptomatic bacteriuria strain 83972 colonization in the pig model. Catheter-promoted colonization protects against experimental UTI in 50% of pigs, confirming the antagonistic effect of the strain. This 50% protection rate mirrors findings from clinical studies suggesting the translatability of results from pigs to humans. Prophylactic colonization with the 83972 emerges as a potential strategy to reduce UTI risk, particularly in catheterized individuals, potentially reducing the need for prolonged antibiotic treatment.

Roos, V., et al., The asymptomatic bacteriuria Escherichia coli strain 83972 outcompetes uropathogenic E. coli strains in human urine. Infect Immun, 2006. 74(1): p. 615-24.
Nielsen, TK., et al., A porcine model for urinary tract infection, Front Microbiol, 2019. 10: p. 2564
Mak, Q., et al., Competitive Inoculation as an Effective Prophylaxis Against Recurrent Urinary Tract Infections: A Systematic Review. Int Neurourol J, 2023. 27(2): p. 79-87.

Continence 12S (2024) 101588
DOI: 10.1016/j.cont.2024.101588