# Impact of Foreign Bodies on Infection Susceptibility, Disease and Mucosal Remodeling of the Urinary Tract

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $519,244

## Abstract

SUMMARY/ABSTRACT
The rising rate of antibiotic resistance is increasingly complicating treatment for infections that, not long ago,
were easily treated. Prominent among these are catheter-associated urinary tract infections (CAUTIs),
which are the most common hospital-associated infection (HAI), and infections of ureteral stents. Over 15
million UTIs occur in the USA each year with accompanying deterioration in the quality of life and increased
health care costs. As a result, 15% of all antibiotics prescribed are for the treatment of UTIs, making these
infections a leading cause of antibiotic use. Complicating treatment decisions for CAUTI/stent-related infections
is that most of these infections are polymicrobial, with multiple bacterial species simultaneously colonizing the
implant. Current treatment guidelines typically focus on a single infecting organism and do not consider the
underlying polymicrobial foundation of the infection, as reflected by the fact that treatment is often ineffective,
requires the removal and replacement with a new catheter/stent, which typically then becomes infected by the
same consortia of bacterial species. There is a significant gap in knowledge of the specific composition of
these consortia, including fastidious species not amenable to detection by traditional approaches. Other
knowledge gaps include: i) the mechanisms that promote and sustain these polymicrobial infections; ii) which
communities/members are responsible for symptoms; iii) why certain consortia show resilience and reappear
even in the presence of antibiotic treatment; and iv) development of antibiotic and antibiotic-sparing strategies
that efficiently disrupt the cycle of polymicrobial infection on urinary catheters and stents. To address this
problem, experimental murine CAUTI models have been developed for several prominent Gram-negative and
Gram-positive uropathogens, including important multi-drug resistant (MDR) genera such as Enterococcus,
Staphylococcus, Klebsiella and Acinetobacter and cutting-edge small molecule therapeutics and
immunotherapies have been developed that are highly effective in murine monomicrobial CAUTI models. This
proposal will build upon this foundation to: i) characterize human samples from patients with long-term
indwelling catheters or stents using a third-generation metagenomic sequencing approach to determine (in <7
hours from sample collection) all members of the infecting consortia and their antibiotic resistance profiles; as
proof of concept same day diagnosis and antibiotic prescription in the clinical setting; ii) correlate measures of
UTI symptomatology and disease outcomes with specific community members; iii) use mouse and in vitro
biofilm models to investigate mechanisms of bacterial-bacterial interactions critical in catheter-associated
polymicrobial communities; and iv) investigate the ability of therapeutics, known to be efficacious against one
species, to treat polymicrobial CAUTIs. These studies will...

## Key facts

- **NIH application ID:** 10775807
- **Project number:** 5R01DK051406-25
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Michael G. Caparon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $519,244
- **Award type:** 5
- **Project period:** 1997-01-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10775807

## Citation

> US National Institutes of Health, RePORTER application 10775807, Impact of Foreign Bodies on Infection Susceptibility, Disease and Mucosal Remodeling of the Urinary Tract (5R01DK051406-25). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10775807. Licensed CC0.

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