# Proteus mirabilis RTX proteins: Role in polymicrobial biofilm formation and pathogenesis of catheter associated urinary tract infection

> **NIH NIH F32** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2024 · $74,284

## Abstract

Project summary/abstract
Catheter-associated urinary tract infections (CAUTI) are among the most common nosocomial infections and are often
caused by Proteus mirabilis. CAUTIs are also often polymicrobial, and the most common and persistent co-colonizing
partners are P. mirabilis and Enterococcus faecalis. Polymicrobial CAUTIs are typically more severe and associated with
increased patient risk, treatment failure, and secondary bacteremia. The prevalence of co-colonization of P. mirabilis with
and E. faecalis combined with the increased severity of disease suggest that disrupting polymicrobial interactions between
these species could be beneficial for enhancing treatment efficacy. There is a fundamental gap in knowledge in current
understanding of mechanisms and clinical relevance of polymicrobial interactions with respect to CAUTI progression and
disease severity. Addressing this gap has the potential to inform development of novel therapeutics to disrupt disease-
enhancing interactions and guiding best practices for clinical interventions. Our preliminary data indicate that
polymicrobial biofilms formed by P. mirabilis and E. faecalis exhibit increased biomass and antibiotic resistance and
revealed P. mirabilis RTX proteins as the most enriched factor in the polymicrobial biofilm. The central hypothesis of this
proposal is that P. mirabilis RTX proteins form an integral structural component of the polymicrobial biofilm and mediate
aggregation with other uropathogens, thereby contributing to the establishment and severity of polymicrobial CAUTI. We
will address this hypothesis by completing two specific aims: 1) Examine the expression of P. mirabilis RTX proteins
during polymicrobial biofilm formation and determine their contribution to biofilm architecture, adhesion, and mediating
bacteria-bacteria interactions. 2) Determine the contribution of P. mirabilis RTX proteins to pathogenesis of polymicrobial
CAUTI. In terms of the first aim, the role of P. mirabilis RTX proteins in polymicrobial biofilms are already underway
utilizing the clinically relevant P. mirabilis HI4320 strain. The media conditions, time-scale, and polymicrobial mixtures
in which P. mirabilis RTX proteins mediate attachment to abiotic and biotic surfaces and biofilm formation will be
determined utilizing traditional 24-well plate biofilm assay and the more physiologically-relevant glass bladder model. A
major training goal of this project is the implementation of high-resolution microscopy techniques to examine spatial
distribution of bacteria within polymicrobial catheter biofilms. Together, this aim will provide insight into the role of P.
mirabilis RTX proteins in polymicrobial biofilms as well as development of a new protocol for visualizing intact biofilms
on clinically relevant surfaces. For the second aim, the established mouse model of CAUTI will be utilized to determine
the role of P. mirabilis RTX proteins in establishment, persistence, and pathogenesis of polymicro...

## Key facts

- **NIH application ID:** 10901465
- **Project number:** 1F32AI183755-01
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Benjamin Carter Hunt
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $74,284
- **Award type:** 1
- **Project period:** 2024-06-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10901465

## Citation

> US National Institutes of Health, RePORTER application 10901465, Proteus mirabilis RTX proteins: Role in polymicrobial biofilm formation and pathogenesis of catheter associated urinary tract infection (1F32AI183755-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10901465. Licensed CC0.

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