# Pseudomonas aeruginosa quorum sensing

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $311,000

## Abstract

Project Summary
Quorum sensing (QS) is a broadly distributed intercellular communication method used by bacteria to
coordinate group activities. The opportunistic human pathogen Pseudomonas aeruginosa uses QS to regulate
the production of numerous secreted products that include virulence factors, antibiotics, and proteases. The
ability of P. aeruginosa to alter its behavior as a group contributes to the difficulty of treating this bacterium in
diseases such as cystic fibrosis, in which it establishes chronic airway infections. In P. aeruginosa, QS is
mediated in part by the transcription factors LasR and RhlR, which respond to acyl-homoserine lactone
signals. In laboratory strains, LasR regulates RhlR, and together they control the transcription of hundreds of
genes. LasR mutants are common in CF (although RhlR mutants are not usually observed) implying
inactivation of QS in these isolates. However, in many P. aeruginosa isolates from cystic fibrosis, RhlR activity
is not dependent on LasR and many LasR-null isolates still engage in acyl-homoserine lactone QS.
The presence of active RhlR QS in these strains implies that QS is important for the regulation of certain
factors within the CF lung. This proposal uses a large collection of P. aeruginosa isolates from cystic fibrosis
patients to explore adaptations P. aeruginosa makes to preserve QS despite lasR mutation. The experiments
described in this proposal ask: 1) what are the genes regulated by QS transcription factors and what is the
“core” QS regulon of clinical isolates; 2) what are the genetic changes that allow for LasR-independent RhlR
activation in these clinical isolates and what are the direct gene targets of RhlR?; and 3) what are the
molecular mechanisms that prevent RhlR mutants from emerging in populations of P. aeruginosa?
The answers to these questions will give a more complete picture of QS in clinical P. aeruginosa, and guide
efforts to target QS or QS-regulated genes to manage and treat bacterial populations in human disease.

## Key facts

- **NIH application ID:** 9840487
- **Project number:** 5R01GM125714-03
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Ajai Dandekar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $311,000
- **Award type:** 5
- **Project period:** 2018-01-05 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9840487

## Citation

> US National Institutes of Health, RePORTER application 9840487, Pseudomonas aeruginosa quorum sensing (5R01GM125714-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9840487. Licensed CC0.

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