# Role of PrrF and PrrH regulation in Pseudomonas aeruginosa pathogenesis

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $423,247

## Abstract

PROJECT SUMMARY
Pseudomonas aeruginosa is a versatile bacterial pathogen that causes life-threatening acute and chronic
infections in diverse patient populations. Complicating treatment is the ability of P. aeruginosa to resist the
majority of antimicrobial therapies. It is therefore critical to identify virulence properties that can be targeted for
the development of novel therapeutics. Several studies demonstrate the importance of iron homeostasis for P.
aeruginosa pathogenesis. Recent work from our lab shows that the P. aeruginosa prrF chromosomal locus,
which encodes the iron-responsive PrrF1 and PrrF2 small regulatory RNAs (sRNAs), is required for acute lung
infection in mice. The PrrF1 and PrrF2 sRNAs contribute to iron homeostasis by repressing the expression of
iron-utilizing pathways when this nutrient is limiting. This “iron sparing response” further impacts diverse
virulence properties, including quorum sensing and biofilm formation. The prrF locus produces a distinct sRNA
(PrrH) that is regulated by heme, an abundant source of iron in the human body, thus linking iron and heme
homeostasis pathways of P. aeruginosa. While our studies have established the broad impact of this locus on
P. aeruginosa physiology and virulence, the mechanisms by which the individual sRNAs transcribed from this
locus mediate gene expression and pathogenesis remain unknown. Based on our preliminary and published
studies, we hypothesize that the PrrF and PrrH sRNAs play critical yet distinct roles in regulating P.
aeruginosa iron homeostasis and virulence. We will test our hypothesis by 1) identifying PrrF target mRNAs
responsible for virulence attenuation of the ΔprrF1,2 mutant; 2) determining the genetic basis of heme
regulated expression via the PrrH sRNA; and 3) defining the mechanisms by which PrrF and PrrH regulate
gene expression. These studies will define the specific mechanisms by which the prrF-transcribed sRNAs
mediate iron homeostasis and virulence of P. aeruginosa.

## Key facts

- **NIH application ID:** 9989757
- **Project number:** 5R01AI123320-05
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Amanda Gail Oglesby
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $423,247
- **Award type:** 5
- **Project period:** 2016-09-23 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989757

## Citation

> US National Institutes of Health, RePORTER application 9989757, Role of PrrF and PrrH regulation in Pseudomonas aeruginosa pathogenesis (5R01AI123320-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9989757. Licensed CC0.

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