# Mechanistic basis of bacteriophages for the decolonization of vancomycin resistant enterococci in the intestine

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2024 · $457,458

## Abstract

PROJECT SUMMARY
Bacteriophages (phages) are gaining traction as antibacterial therapeutics largely due to several high profile
uses as emergency-approved experimental biologics. A perceived problem with phage therapy is that the
development of bacterial phage resistance will curtail the use of phages as clinically relevant therapies. This
conclusion overlooks a fundamental flaw in the development of phage resistance, that is, bacteria often incur
reduced fitness as a result of acquired phage resistance. These fitness tradeoffs include enhanced antibiotic
susceptibility, reduced virulence, and the inability to stably colonize their host. The work described in this
proposal will capitalize on the emergence of phage resistance as a means to successfully treat recalcitrant
opportunistic pathogens that reside in the intestine. We will use the Gram-positive intestinal commensals and
opportunistic pathogens Enterococcus faecalis and Enterococcus faecium as model organisms to determine
how phage resistance phenotypes influence their fitness in the intestine and whether these outcomes can be
leveraged as novel therapeutic approaches. Specifically, we will define the mechanisms that drive phage
resistance fitness defects of E. faecalis and E. faecium within the intestine by executing three specific aims: 1)
to define the mechanism(s) driving the intestinal colonization deficiency of phage resistant strains harboring cell
surface exopolysaccharide mutations; 2) to examine how phage-mediated mutations in the peptidoglycan
hydrolase gene sagA result in antibiotic sensitivity; and 3) to determine if phage-antibiotic combinations reduce
enterococcal intestinal colonization.

## Key facts

- **NIH application ID:** 10935986
- **Project number:** 5R01AI141479-07
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Breck A Duerkop
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $457,458
- **Award type:** 5
- **Project period:** 2018-09-14 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10935986

## Citation

> US National Institutes of Health, RePORTER application 10935986, Mechanistic basis of bacteriophages for the decolonization of vancomycin resistant enterococci in the intestine (5R01AI141479-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10935986. Licensed CC0.

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