# Developing synergistic antibiotic and phage cocktails to target bacterial pathogens

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA-IRVINE · 2021 · $188,791

## Abstract

Project Summary
Bacteriophages have evolved for many years with their bacterial hosts, and recent evidence shows that this
battle has been ongoing in the human microbiome. There are 38 trillion bacteria that live in and on the human
body, and they are accompanied by at least 10 times as many viruses. Many of those viruses are
bacteriophages (phages). We now know that much of the unique diversity found in the human microbiome is
imparted by those phages, which help to generate bacterial diversity as their hosts evolve to subvert phage
attacks. The fact that the human body is inhabited by so many phages belies how successfully phages have
evolved to identify and kill their hosts in humans.
Phages have recently gained renewed interest with the rise of antimicrobial resistance (AMR) in bacteria.
There are several different bacteria such as Carbapenem Resistant Enterobacteriaceae and Vancomycin
Resistant Enterococcus that develop or acquire antibiotic resistance, becoming resistant to numerous
commonly prescribed antibiotics. Because antibiotics can significantly alter the microbiome of humans
(potentially resulting in significant long term health consequence), and the significant recent rises in AMR, the
focus in developing therapeutics against bacterial pathogens has shifted to microbiome and AMR sparing
alternatives such as phages. Understanding how we may uses phages to eradicate pathogens such as
Enterococcus that live in our microbiomes, yet sometimes can become highly antibiotic resistant pathogens,
has become of critical importance.
We have assembled a multidisciplinary group of researchers with expertise in host-phage interactions (Dr.
Whiteson), and clinical microbiology and the human microbiome (Dr. Pride) to isolate and identify phages
effective against this understudied pathogen. We have preliminary data indicating that Enterococcus evolves in
predictable ways to avoid phages, which we plan to take advantage of to identify characteristics of phages,
phage cocktails, and phage-antibiotic combinations that work cooperatively to eradicate this pathogen.
In this project, we will address three main questions. 1. Can we identify lytic Enterococcus phages from the
human microbiome and do phages isolated from humans have broad range across Enterococcus species? 2.
Can we identify the different mechanisms of resistance that bacterial hosts evolve against Enterococcus
phages, and can these mechanisms inform cocktail design? 3. Will the use of antibiotics that have similar
targets as some Enterococcus phages work synergistically to produce more effective therapeutic
combinations? By addressing these three critical questions, we can significantly advance our knowledge of
host-phage interactions, develop synergistic antibiotic-phage and phage-phage cocktails, and identify phage
combinations that significantly reduce the emergence of bacteria resistant to phages and antibiotics. Our
approach has the potential to help combat the bacteria responsible for...

## Key facts

- **NIH application ID:** 10104442
- **Project number:** 5R21AI149354-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** David Tevis Pride
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $188,791
- **Award type:** 5
- **Project period:** 2020-02-11 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10104442

## Citation

> US National Institutes of Health, RePORTER application 10104442, Developing synergistic antibiotic and phage cocktails to target bacterial pathogens (5R21AI149354-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10104442. Licensed CC0.

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