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Kinetic Model for Signal Binding to the Quorum Sensing Regulator LasR

We propose a kinetic model for the activation of the las regulon in the opportunistic pathogen Pseudomonas aeruginosa. The model is based on in vitro data and accounts for the LasR dimerization and consecutive activation by binding of two OdDHL signal molecules. Experimentally, the production of the...

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Autores principales: Claussen, Anetta, Jakobsen, Tim Holm, Bjarnsholt, Thomas, Givskov, Michael, Welch, Martin, Ferkinghoff-Borg, Jesper, Sams, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3742191/
https://www.ncbi.nlm.nih.gov/pubmed/23807499
http://dx.doi.org/10.3390/ijms140713360
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author Claussen, Anetta
Jakobsen, Tim Holm
Bjarnsholt, Thomas
Givskov, Michael
Welch, Martin
Ferkinghoff-Borg, Jesper
Sams, Thomas
author_facet Claussen, Anetta
Jakobsen, Tim Holm
Bjarnsholt, Thomas
Givskov, Michael
Welch, Martin
Ferkinghoff-Borg, Jesper
Sams, Thomas
author_sort Claussen, Anetta
collection PubMed
description We propose a kinetic model for the activation of the las regulon in the opportunistic pathogen Pseudomonas aeruginosa. The model is based on in vitro data and accounts for the LasR dimerization and consecutive activation by binding of two OdDHL signal molecules. Experimentally, the production of the active LasR quorum-sensing regulator was studied in an Escherichia coli background as a function of signal molecule concentration. The functional activity of the regulator was monitored via a GFP reporter fusion to lasB expressed from the native lasB promoter. The new data shows that the active form of the LasR dimer binds two signal molecules cooperatively and that the timescale for reaching saturation is independent of the signal molecule concentration. This favors a picture where the dimerized regulator is protected against proteases and remains protected as it is activated through binding of two successive signal molecules. In absence of signal molecules, the dimerized regulator can dissociate and degrade through proteolytic turnover of the monomer. This resolves the apparent contradiction between our data and recent reports that the fully protected dimer is able to “degrade” when the induction of LasR ceases.
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spelling pubmed-37421912013-08-13 Kinetic Model for Signal Binding to the Quorum Sensing Regulator LasR Claussen, Anetta Jakobsen, Tim Holm Bjarnsholt, Thomas Givskov, Michael Welch, Martin Ferkinghoff-Borg, Jesper Sams, Thomas Int J Mol Sci Article We propose a kinetic model for the activation of the las regulon in the opportunistic pathogen Pseudomonas aeruginosa. The model is based on in vitro data and accounts for the LasR dimerization and consecutive activation by binding of two OdDHL signal molecules. Experimentally, the production of the active LasR quorum-sensing regulator was studied in an Escherichia coli background as a function of signal molecule concentration. The functional activity of the regulator was monitored via a GFP reporter fusion to lasB expressed from the native lasB promoter. The new data shows that the active form of the LasR dimer binds two signal molecules cooperatively and that the timescale for reaching saturation is independent of the signal molecule concentration. This favors a picture where the dimerized regulator is protected against proteases and remains protected as it is activated through binding of two successive signal molecules. In absence of signal molecules, the dimerized regulator can dissociate and degrade through proteolytic turnover of the monomer. This resolves the apparent contradiction between our data and recent reports that the fully protected dimer is able to “degrade” when the induction of LasR ceases. Molecular Diversity Preservation International (MDPI) 2013-06-27 /pmc/articles/PMC3742191/ /pubmed/23807499 http://dx.doi.org/10.3390/ijms140713360 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland http://creativecommons.org/licenses/by/3.0 This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Claussen, Anetta
Jakobsen, Tim Holm
Bjarnsholt, Thomas
Givskov, Michael
Welch, Martin
Ferkinghoff-Borg, Jesper
Sams, Thomas
Kinetic Model for Signal Binding to the Quorum Sensing Regulator LasR
title Kinetic Model for Signal Binding to the Quorum Sensing Regulator LasR
title_full Kinetic Model for Signal Binding to the Quorum Sensing Regulator LasR
title_fullStr Kinetic Model for Signal Binding to the Quorum Sensing Regulator LasR
title_full_unstemmed Kinetic Model for Signal Binding to the Quorum Sensing Regulator LasR
title_short Kinetic Model for Signal Binding to the Quorum Sensing Regulator LasR
title_sort kinetic model for signal binding to the quorum sensing regulator lasr
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3742191/
https://www.ncbi.nlm.nih.gov/pubmed/23807499
http://dx.doi.org/10.3390/ijms140713360
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