A secreted regulatory protein couples transcription to the secretory activity of the Pseudomonas aeruginosa type III secretion system

Mark L Urbanowski; Guinevere L Lykken; Timothy L Yahr

doi:10.1073/pnas.0504405102

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A secreted regulatory protein couples transcription to the secretory activity of the Pseudomonas aeruginosa type III secretion system

Journal article

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A secreted regulatory protein couples transcription to the secretory activity of the Pseudomonas aeruginosa type III secretion system

Mark L Urbanowski, Guinevere L Lykken and Timothy L Yahr

Proceedings of the National Academy of Sciences - PNAS, Vol.102(28), pp.9930-9935

07/12/2005

DOI: 10.1073/pnas.0504405102

PMCID: PMC1175016

PMID: 15985546

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Abstract

The type III secretion system (T3SS) of Pseudomonas aeruginosa is an important virulence determinant. Transcription of the T3SS is highly regulated and intimately coupled to the activity of the type III secretion channel. The secretion channel is generally closed, and transcription is repressed. Inducing signals such as calcium depletion, however, open the secretion channel and derepress transcription of the T3SS. The coupling of transcription with secretion requires three previously identified cytoplasmic regulatory proteins. ExsA is a DNA-binding protein required for transcriptional activation of the entire T3SS. The second regulatory protein, ExsD, functions as anti-activator by directly binding to ExsA. Finally, ExsC functions as an anti-anti-activator by directly binding to and inhibiting ExsD. Although the regulatory roles of ExsC, ExsD, and ExsA were defined through these previous studies, the mechanism of coupling transcription to secretion was unclear. We now report the identification of ExsE as a secreted regulator of the T3SS and provide evidence that ExsE functions as a direct inhibitor of ExsC. When the secretion channel is closed, ExsE is complexed with ExsC in the cytoplasm, and transcription of the T3SS is repressed by sequestration of ExsA by ExsD. We propose that the secretion of ExsE provides an initiating signal that results in an equilibrium shift whereby ExsC becomes preferentially bound to ExsD, thus allowing liberated ExsA to activate transcription of the T3SS. The presence of ExsE homologs in the T3SSs of other bacterial species suggests that this mechanism of coupling transcription to secretion may be commonly used.

Cell Fractionation

Electrophoresis, Polyacrylamide Gel

beta-Galactosidase

Immunoblotting

DNA-Binding Proteins - metabolism

Two-Hybrid System Techniques

Pseudomonas aeruginosa - metabolism

Plasmids - genetics

Bacterial Proteins - metabolism

Signal Transduction - physiology

Trans-Activators - metabolism

Gene Expression Regulation, Bacterial

Repressor Proteins - metabolism

Details

Title: Subtitle: A secreted regulatory protein couples transcription to the secretory activity of the Pseudomonas aeruginosa type III secretion system
Creators: Mark L Urbanowski - Department of Microbiology, W. M. Keck Microbial Communities and Cell Signaling Program, University of Iowa, Iowa City, IA 52242
Guinevere L Lykken
Timothy L Yahr
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.102(28), pp.9930-9935
DOI: 10.1073/pnas.0504405102
PMID: 15985546
PMCID: PMC1175016
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences; United States
Grant note: R01 AI 55042 / NIAID NIH HHS R01 AI055042 / NIAID NIH HHS
Language: English
Date published: 07/12/2005
Academic Unit: Microbiology and Immunology
Record Identifier: 9984001209902771

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