# Phages as drivers of pathogenicity: selective impacts and molecular targets of clinical Pseudomonas aeruginosa phages

> **NIH NIH R21** · GEORGIA INSTITUTE OF TECHNOLOGY · 2020 · $197,250

## Abstract

Project Summary
Chronic infections are a major and rising medical challenge, often characterized by
varying pathogen virulence and drug resistance profiles. Pseudomonas aeruginosa (PA)
is a key driver of chronic infection mortality, including in our focal system of lung
infections in Cystic Fibrosis (CF) patients. While PA has been studied extensively, the
role of naturally occurring bacteriophages (phages) in shaping the evolutionary dynamics
of chronic infections has been largely overlooked. It is recognized that within the CF lung
there are high levels of phage, and in vitro work suggests that phage are potential
drivers of bacterial diversity and of shifts in virulence. Phages bind to specific bacterial
surface factors to initiate infection, including receptors that are important for virulence
and antibiotic resistance, such as LPS, type IV pili, or efflux pumps. Thus phages can in
principle impart selection on a pathogenic bacterium that impacts virulence and antibiotic
resistance changing the trajectory of chronic infections. While naturally present phages
have been largely overlooked in an infection context, phage therapy continues to draw
attention and mixed results. In order to understand the drivers of pathogen evolution in
an infection context, and to assess the potential for phage therapy as a curative and/or
selective agent, it is essential to map the selective impacts and molecular targets of
phages within infection settings. The overarching hypothesis of this study is that
introduced and endemic phages shape the evolution of pathogen surface factors, which
in turn define pathogen virulence and drug / phage resistance. This project will test this
hypothesis using an array of genomic, phenotypic and modeling techniques with the goal
of opening paths towards improved mechanisms of control.

## Key facts

- **NIH application ID:** 9825502
- **Project number:** 5R21AI143296-02
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Samuel Paul Brown
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $197,250
- **Award type:** 5
- **Project period:** 2018-11-20 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9825502

## Citation

> US National Institutes of Health, RePORTER application 9825502, Phages as drivers of pathogenicity: selective impacts and molecular targets of clinical Pseudomonas aeruginosa phages (5R21AI143296-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9825502. Licensed CC0.

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