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A new regulator of pathogenicity (bvlR) is required for full virulence and tight microcolony formation in Pseudomonas aeruginosa

A new regulator of pathogenicity (bvlR) is required for full virulence and tight microcolony formation in Pseudomonas aeruginosa
A new regulator of pathogenicity (bvlR) is required for full virulence and tight microcolony formation in Pseudomonas aeruginosa

LysR-type transcriptional regulators (LTTRs) are the most common family of transcriptional regulators found in the opportunistic pathogen Pseudomonas aeruginosa. They are known to regulate a wide variety of virulence determinants and have emerged recently as positive global regulators of pathogenicity in a broad spectrum of important bacterial pathogens. However, in spite of their key role in modulating expression of key virulence determinants underpinning pathogenic traits associated with the process of infection, surprisingly few are found to be transcriptionally altered by contact with host cells. BvlR (PA14_26880) an LTTR of previously unknown function, has been shown to be induced in response to host cell contact, and was therefore investigated for its potential role in virulence. BvlR expression was found to play a pivotal role in the regulation of acute virulence determinants such as type III secretion system and exotoxin A production. BvlR also played a key role in P. aeruginosa pathogenicity within the Caenorhabditis elegans acute model of infection. Loss of BvlR led to an inability to form tight microcolonies, a key step in biofilm formation in the cystic fibrosis lung, although surface attachment was increased. Unusually for LTTRs, BvlR was shown to exert its influence through the transcriptional repression of many genes, including the virulence-associated cupA and alg genes. This highlights the importance of BvlR as a new virulence regulator in P. aeruginosa with a central role in modulating key events in the pathogen-host interactome.

ADP Ribose Transferases/metabolism, Animals, Bacterial Adhesion, Bacterial Proteins/genetics, Bacterial Secretion Systems, Bacterial Toxins/metabolism, Biofilms/growth & development, Caenorhabditis elegans/microbiology, Exotoxins/metabolism, Gene Expression Regulation, Bacterial, Homeostasis, Humans, Pseudomonas Infections/microbiology, Pseudomonas aeruginosa/genetics, Repressor Proteins/genetics, Transcription Factors/genetics, Virulence, Virulence Factors/genetics, Pseudomonas aeruginosa Exotoxin A
1350-0872
1488-1500
McCarthy, Ronan R
0b2cf2e0-b0ff-4c92-aa04-92d91182d1f2
Mooij, Marlies J
68e42335-eee1-44cb-827b-7926e0bab319
Reen, F Jerry
026cb870-1c0e-4e5e-ab28-69bc2daa6421
Lesouhaitier, Olivier
46ae9ed9-5198-4598-8d89-e8c14b6da632
O'Gara, Fergal
689ec48f-a942-44a6-8c88-7d13f1768122
McCarthy, Ronan R
0b2cf2e0-b0ff-4c92-aa04-92d91182d1f2
Mooij, Marlies J
68e42335-eee1-44cb-827b-7926e0bab319
Reen, F Jerry
026cb870-1c0e-4e5e-ab28-69bc2daa6421
Lesouhaitier, Olivier
46ae9ed9-5198-4598-8d89-e8c14b6da632
O'Gara, Fergal
689ec48f-a942-44a6-8c88-7d13f1768122

McCarthy, Ronan R, Mooij, Marlies J, Reen, F Jerry, Lesouhaitier, Olivier and O'Gara, Fergal (2014) A new regulator of pathogenicity (bvlR) is required for full virulence and tight microcolony formation in Pseudomonas aeruginosa. Microbiology (Reading, England), 160 (Pt 7), 1488-1500. (doi:10.1099/mic.0.075291-0).

Record type: Article

Abstract

LysR-type transcriptional regulators (LTTRs) are the most common family of transcriptional regulators found in the opportunistic pathogen Pseudomonas aeruginosa. They are known to regulate a wide variety of virulence determinants and have emerged recently as positive global regulators of pathogenicity in a broad spectrum of important bacterial pathogens. However, in spite of their key role in modulating expression of key virulence determinants underpinning pathogenic traits associated with the process of infection, surprisingly few are found to be transcriptionally altered by contact with host cells. BvlR (PA14_26880) an LTTR of previously unknown function, has been shown to be induced in response to host cell contact, and was therefore investigated for its potential role in virulence. BvlR expression was found to play a pivotal role in the regulation of acute virulence determinants such as type III secretion system and exotoxin A production. BvlR also played a key role in P. aeruginosa pathogenicity within the Caenorhabditis elegans acute model of infection. Loss of BvlR led to an inability to form tight microcolonies, a key step in biofilm formation in the cystic fibrosis lung, although surface attachment was increased. Unusually for LTTRs, BvlR was shown to exert its influence through the transcriptional repression of many genes, including the virulence-associated cupA and alg genes. This highlights the importance of BvlR as a new virulence regulator in P. aeruginosa with a central role in modulating key events in the pathogen-host interactome.

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More information

Published date: July 2014
Additional Information: © 2014 The Authors.
Keywords: ADP Ribose Transferases/metabolism, Animals, Bacterial Adhesion, Bacterial Proteins/genetics, Bacterial Secretion Systems, Bacterial Toxins/metabolism, Biofilms/growth & development, Caenorhabditis elegans/microbiology, Exotoxins/metabolism, Gene Expression Regulation, Bacterial, Homeostasis, Humans, Pseudomonas Infections/microbiology, Pseudomonas aeruginosa/genetics, Repressor Proteins/genetics, Transcription Factors/genetics, Virulence, Virulence Factors/genetics, Pseudomonas aeruginosa Exotoxin A

Identifiers

Local EPrints ID: 506093
URI: http://eprints.soton.ac.uk/id/eprint/506093
ISSN: 1350-0872
PURE UUID: 06761275-fe5e-40bd-a61b-4c5fc6e653f4
ORCID for Ronan R McCarthy: ORCID iD orcid.org/0000-0002-7480-6352

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Date deposited: 28 Oct 2025 18:24
Last modified: 29 Oct 2025 03:15

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Contributors

Author: Ronan R McCarthy ORCID iD
Author: Marlies J Mooij
Author: F Jerry Reen
Author: Olivier Lesouhaitier
Author: Fergal O'Gara

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