Proteasome-mediated degradation of rhlr controls quorum sensing progression in pseudomonas aeruginosa
Active Project Grant Awarded Last action
- Award ID
- F31AI197475
- Recipient
-
The Research Foundation For The State University Of New York UEI NHH3T1Z96H29 Part of The Research Foundation For The State University Of New York
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $80,796
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 3% complete
- Originally
- Place of performance
- Albany, NY 12222, USA
Award details come from USAspending.gov.
Description
- Abstract
- Pseudomonas aeruginosa is a gram-negative opportunistic pathogen and a major public health threat, particularly in healthcare settings where IT infects immunocompromised patients. Its virulence is driven by quorum sensing (QS), a cell density-dependent signaling mechanism that regulates biofilm formation and virulence factor production. Central to QS are luxr-type transcription factors, which bind acyl-homoserine lactone (AHL) signals to regulate gene expression. Uniquely, the rhlr receptor requires both its AHL ligand and the accessory protein pqse for maximal transcriptional activation. We recently found that in the absence of pqse, rhlr is degraded by the LON protease, suggesting proteolysis plays a key role in QS regulation. While much research has focused on the transition from low- to high-cell density (LCD to HCD) signaling, how P. Aeruginosa transitions from HCD back to LCD remains poorly understood. This study will address this GAP by investigating how P. Aeruginosa "breaks" its quorum through rhlr regulation. I hypothesize that rhlr contains a degron, a signal recognized by LON and potentially other AAA+ proteases, that controls its stability and facilitates the transition from HCD to LCD. The goal of this work is to elucidate the mechanism of rhlr degradation and its impact on QS-regulated traits. Aim 1: mechanistic insights into protease-mediated regulation of rhlr and its accessory protein pqse in P. Aeruginosa. I will determine how LON and other AAA+ proteases recognize and degrade rhlr. I hypothesize that a degron in rhlr becomes exposed in the absence of pqse, leading to proteolysis. Using site-directed mutagenesis, I will identify degron residues essential for protease recognition and assess whether pqse binding shields this degron. In vitro degradation and protein stability assays will quantify rhlr degradation kinetics and identify additional proteases involved. Aim 2: temporal regulation of rhlr-dependent traits as a function of protease-mediated degradation. I will examine how rhlr degradation affects QS-regulated behaviors such as biofilm formation and virulence factor production. Using RNA-sequencing, I will quantify gene expression dynamics in wild-type and protease- deficient strains across cell densities. I will also assess stabilized versus degradation-prone rhlr mutants to determine how rhlr turnover influences the persistence of QS activity at HCD and its termination at LCD.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $576 | |
| Amendment | $0 | |
| Amendment | $576 | |
| Amendment | $39,822 | |
| Original award | $39,822 |
Quick answers
Who received award F31AI197475?
F31AI197475 was awarded to The Research Foundation For The State University Of New York by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on September 30, 2026.
How much is award F31AI197475 worth?
$80,796 has been obligated on F31AI197475.
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