# Regulation of the Pseudomonas aeruginosa protease PrpL by temperature and iron

> **NIH NIH F31** · EMORY UNIVERSITY · 2023 · $47,694

## Abstract

PROJECT SUMMARY/ABSTRACT
The bacterial pathogen Pseudomonas aeruginosa is a frequent cause of nosocomial infections and life-
threatening lung infections in people with the genetic disorder cystic fibrosis. P. aeruginosa infections are difficult
and costly to treat due to inherent and acquired antibiotic resistance, underscoring the need for new treatments.
A better understanding of how P. aeruginosa causes infections will be instrumental for this. P. aeruginosa
survives in a human host and causes disease by producing multiple virulence factors. One such virulence factor,
the serine protease PrpL, causes severe tissue damage and degrades components of the immune system.
Expression of prpL is regulated by two environmental factors experienced by P. aeruginosa during an infection:
low iron availability and temperature. Expression of prpL is upregulated by low iron availability through a known
mechanism and downregulated at 37C compared to 25C through an unknown mechanism. The Goldberg Lab
has found that the transcription factors MvaT/MvaU and LasR are required for this prpL thermoregulation, but
the mechanism of prpL thermoregulation remains to be fully elucidated. How iron and temperature coregulate
prpL and the importance of this for P. aeruginosa virulence is also unknown. Given that low iron availability
upregulates prpL while 37C conditions downregulate it, iron and temperature may balance PrpL production and
be important for P. aeruginosa virulence. Based on these findings, I hypothesize that thermoregulation of
prpL occurs through temperature-dependent binding of MvaT/MvaU and LasR to the prpL promoter and
that iron/temperature coregulation of prpL is important for P. aeruginosa virulence. I will test this
hypothesis using genetic and biochemical approaches, and an animal model of infection. In Aim 1, I will define
the prpL thermoregulatory mechanism by determining if MvaT/MvaU and LasR positively or negatively regulate
prpL transcription at 25C and 37C, and by characterizing the impact of temperature on the binding of
MvaT/MvaU and LasR to the prpL promoter. In Aim 2, I will determine how temperatures balances production
and activity of PrpL by measuring prpL gene expression, the amount of PrpL secreted, and the total enzymatic
activity of secreted PrpL across a 20C-42C range. In Aim 3, I will characterize the role of prpL iron/temperature
coregulation in P. aeruginosa virulence by infecting larvae of the moth Galleria mellonella. Larvae will be infected
with a P. aeruginosa strain in which prpL is regulated by low iron availability and a strain in which prpL is not,
and larvae from both groups will be housed at 25C and 37C to measure how iron and temperature coregulation
of prpL affects P. aeruginosa virulence. A mechanistic study of prpL thermoregulation will address a major gap
in the knowledge of virulence factor thermoregulation in P. aeruginosa. Understanding how PrpL is regulated by
temperature and iron to facilitate P. aeru...

## Key facts

- **NIH application ID:** 10679767
- **Project number:** 1F31AI172335-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Rachel Evans Robinson
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $47,694
- **Award type:** 1
- **Project period:** 2023-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10679767

## Citation

> US National Institutes of Health, RePORTER application 10679767, Regulation of the Pseudomonas aeruginosa protease PrpL by temperature and iron (1F31AI172335-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10679767. Licensed CC0.

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