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

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2020 · $454,151

## Abstract

Project Summary/Abstract
The incidence of multidrug resistant (MDR) bacterial infections is rising. This is particularly relevant for the Gram-
positive bacterium Enterococcus faecalis, an opportunistic pathogen and leading cause of nosocomial
bacteremia. The rise in MDR E. faecalis infections is largely attributed to their ability to resist many antibiotics
including antibiotics of “last resort”, such as vancomycin. E. faecalis is a native inhabitant of the human intestinal
tract which serves as a major reservoir of MDR E. faecalis. Antibiotic depletion of the intestinal microbiota can
facilitate blooms of E. faecalis leading to their enhanced dissemination to the bloodstream and other tissue sites.
In many cases overgrowth of intestinal enterococci is dominated by vancomycin resistant enterococci (VRE)
which severely limits available treatment options. With increasing VRE infections worldwide, it is imperative that
new strategies for therapeutic intervention are explored. An alternative to traditional antibiotics is the use of
biological agents for the treatment of drug resistant bacterial infections. One approach is harnessing
bacteriophages (phages) that infect and kill bacteria. Although phages may hold promise as next generation
therapeutics, we know little of the basic principles of phage infection processes in vivo and how the mammalian
host environment influences phage-bacteria interactions. This project investigates the use of phages for the
decolonization of VRE within its natural intestinal habitat. Using a combination of mouse intestinal colonization
models, molecular genetics and whole genome sequencing, we aim to gain mechanistic insight into how
intestinal selective pressures influence the infectivity and genome evolution of phages during phage-mediated
VRE decolonization. To achieve this goal we will execute three specific aims: 1) Define the intestinal selective
pressures that dictate phage-mediated E. faecalis decolonization, 2) Determine the long-term stability and
genomic evolution of E. faecalis phages in the intestine, and 3) Determine cognate receptors for diverse
E. faecalis phages and delineate receptor function. Understanding intestinal selective pressures and
molecular mechanisms of enterococcal phage infection in vivo will aid in the development of novel phage
therapeutics for the decolonization of enterococci recalcitrant to conventional antibiotics.

## Key facts

- **NIH application ID:** 9983575
- **Project number:** 5R01AI141479-03
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Breck A Duerkop
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $454,151
- **Award type:** 5
- **Project period:** 2018-09-14 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983575

## Citation

> US National Institutes of Health, RePORTER application 9983575, Mechanistic basis of bacteriophages for the decolonization of vancomycin resistant enterococci in the intestine. (5R01AI141479-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9983575. Licensed CC0.

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