# Novel Strategies for Treating Biofilm-Forming Pathogens with Phage Therapy

> **NIH NIH R21** · QUEENS COLLEGE · 2022 · $192,500

## Abstract

Project Summary
The growing antibiotic resistance problem requires that we urgently develop and test new approaches
to controlling bacterial infections. Phage therapy approaches offer great promise, but significant
knowledge gaps currently exist that limit their application. Two issues that currently limit the broader
use of phage therapy are the problem of curating specific lytic phage strains for each infection, and the
difficulty of delivering phages directly to the infection sites where they are needed. We hypothesize that
bacterial pathways that typically promote biofilm-associated growth can be decoupled from the stress-
response pathways capable of inducing resident prophages. By separating these cellular responses,
we propose to stabilize biofilms while also inducing temperate phages already present in the bacterial
genome to enter lytic phase and kill the host cell. In so doing, we effectively bypass the limitations
imposed by finding and delivering strain matched lytic phages to infections, while also developing
approaches that make use of temperate phage therapy approaches. In Aim 1, we propose to determine
biofilm dispersal rates and ascertain how biofilm-associated growth can be manipulated using cellular
pathways. In Aim 2, we will analyze mechanisms by which lysogens can be induced into lytic phase to
kill their hosts without spreading virulence factors beyond the biofilm. In Aim 3, we reinforce the
approaches of the previous aims with an optimized lytic phage ambush of any escaping dispersers.
The goals of this proposal are to develop an innovative, multi-pronged approach to phage therapy for
biofilm-associated bacteria while also increasing overall knowledge of the limits and applicability of
phage therapy.

## Key facts

- **NIH application ID:** 10320958
- **Project number:** 5R21AI156798-02
- **Recipient organization:** QUEENS COLLEGE
- **Principal Investigator:** John Joseph Dennehy
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $192,500
- **Award type:** 5
- **Project period:** 2021-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10320958

## Citation

> US National Institutes of Health, RePORTER application 10320958, Novel Strategies for Treating Biofilm-Forming Pathogens with Phage Therapy (5R21AI156798-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10320958. Licensed CC0.

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