# Regulation of Pseudomonas aeruginosa type III secretion

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2021 · $355,102

## Abstract

Abstract
 The Pseudomonas aeruginosa type III secretion system (T3SS) functions like a molecular
syringe to inject toxins into host cells. The primary cellular targets are phagocytes and epithelial
cells. The injected toxins promote phagocytic avoidance and tissue destruction resulting in
systemic spread of the bacteria and overwhelming sepsis. Deployment of the T3SS is highly
regulated and only activated when bacteria contact host cell surfaces. The overriding hypothesis
guiding the studies is that increased understanding of mechanisms that regulate T3SS gene
expression will lead to the identification of critical steps that can be targeted by anti-virulence
therapeutics, the long term goal of the proposed work. The primary protein required for contact-
dependent activation of the T3SS is a transcription factor called ExsA. Preliminary data
demonstrate that exsA transcription, ExsA synthesis, and ExsA activity are each subject to
control by global regulatory systems. The goals of this proposal are to define novel mechanisms
that control exsA transcription, and possibly ExsA synthesis or activity. Our preliminary data
demonstrate that the 297 bp intergenic region located between exsB and exsA functions in two
capacities. First, the intergenic region contains a Vfr-dependent promoter dedicated to exsA
transcription. Vfr is cAMP-dependent transcription factor previously known to regulate T3SS
gene expression but the mechanism has not been defined. Second, expression of the intergenic
region in trans has a stimulatory effect on T3SS gene expression. Preliminary data suggest that
two small peptides encoded within the intergenic region modulate T3SS gene expression. The
three aims will characterize the stimulatory activity of the intergeneic region and factors that
regulate intergenic promoter activity as follows:
 Aim 1. Characterize the trans-acting functions of ExsF and ExsG.
 Aim 2. Characterize IR promoter activity.
 Aim 3. Determine whether Vfr, MvaT/MvaU, and VqsM function together, antagonistically, or
 independently to modulate IR promoter activity.

## Key facts

- **NIH application ID:** 10076756
- **Project number:** 5R01AI055042-15
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** TIMOTHY L YAHR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $355,102
- **Award type:** 5
- **Project period:** 2003-05-15 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10076756

## Citation

> US National Institutes of Health, RePORTER application 10076756, Regulation of Pseudomonas aeruginosa type III secretion (5R01AI055042-15). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10076756. Licensed CC0.

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