# Conserved Proteus mirabilis genetic requirements for colonization of the catheterized urinary tract

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2021 · $362,866

## Abstract

Project Summary/Abstract
Patients with indwelling urinary catheters have nearly double the mortality rate compared to non-catheterized
patients due to the propensity for adverse outcomes, including functional decline, increased length of stay in
hospital settings, catheter-associated urinary tract infections (CAUTI), and bacteremia. Catheterization also
increases the likelihood of colonization by multidrug-resistant organisms, and antibiotic resistance is increasing
at an alarming rate, making it imperative to identify novel, non-antibiotic treatments for CAUTI and associated
complications. The Gram-negative bacterium Proteus mirabilis is a predominant cause of CAUTI, particularly
during long-term catheterization. CAUTI is also frequently polymicrobial, which can increase risk of severe
disease and bacteremia. There is, however, a fundamental gap in knowledge regarding conserved targets for
treating or preventing disease due to P. mirabilis, particularly during polymicrobial infection. Our preliminary data
clearly demonstrates that the presence of other bacterial species during infection dramatically impacts the genes
required by P. mirabilis for colonization and persistence during CAUTI, especially the metabolic pathways that
are favored by the bacterium for growth and the defense mechanisms that are used to evade host antimicrobial
responses. However, we have uncovered a set of 217 genes encoded by P. mirabilis that provide a fitness
advantage during single-species infection and polymicrobial infection with another Gram-negative bacterium,
Providencia stuartii. Fifty-seven percent of these genes (123/217) are highly conserved in all 106 publically-
available P. mirabilis genomes. The central hypothesis of this proposal is that P. mirabilis encodes a core set
of conserved genes that are critical for establishing CAUTI, regardless of which other bacterial species are
present. We further anticipate that a subset of these factors will be ideal targets for treatment or prevention of
disease. This hypothesis will be tested through three concurrent specific aims. In Aim 1, we will utilize genome-
wide transposon insertion-site sequencing to uncover the impact of co-colonization by two common
uropathogens (Escherichia coli and Enterococcus faecalis) on the genes required by P. mirabilis to colonize the
catheterized urinary tract, including which of the 123 conserved core fitness factors remain important for
establishing infection and whether they are expressed during human CAUTI. In Aims 2 and 3, we will explore
the importance of two pathways that are well-represented in the current set of core fitness factors (amino acid
metabolism and peroxide detoxification) to P. mirabilis pathogenicity. This includes broad characterization of
amino acid availability within the murine urinary tract, with or without an indwelling catheter, and the amino acid
preferences of 5 uropathogens, as well as production of reactive oxygen species by these uropathogens and by
...

## Key facts

- **NIH application ID:** 10165709
- **Project number:** 5R01DK123158-03
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Chelsie Elizabeth Armbruster
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $362,866
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10165709

## Citation

> US National Institutes of Health, RePORTER application 10165709, Conserved Proteus mirabilis genetic requirements for colonization of the catheterized urinary tract (5R01DK123158-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10165709. Licensed CC0.

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