A new transcriptional repressor of the pseudomonas aeruginosa quorum sensing receptor gene lasR
Pseudomonas aeruginosa pathogenic potential is controlled via multiple regulatory pathways, including three quorum sensing (QS) systems. LasR is a key QS signal receptor since it acts as a global transcriptional regulator required for optimal expression of main virulence factors. P. aeruginosa modul...
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| Veröffentlicht in: | PloS one 2013-07, Vol.8 (7), p.e69554 |
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| description | Pseudomonas aeruginosa pathogenic potential is controlled via multiple regulatory pathways, including three quorum sensing (QS) systems. LasR is a key QS signal receptor since it acts as a global transcriptional regulator required for optimal expression of main virulence factors. P. aeruginosa modulates the QS response by integrating this cell density-dependent circuit to environmental and metabolic cues. Hence, QS also controls the adaptation to challenging environmental niches, such as infection sites. However, little is known about the molecular mechanisms connecting QS and other signalling pathways. In this work, DNA-affinity chromatography was used to identify new lasR transcriptional regulators. This approach led to the identification and functional characterization of the TetR-like transcriptional repressor PA3699. This protein was purified and shown to directly bind to the lasR promoter region in vitro. The induction of PA3699 expression in P. aeruginosa PAO1 cultures repressed lasR promoter activity and the production of LasR-dependent virulence factors, such as elastase, pyocyanin, and proteases. These findings suggest a role for PA3699 in P. aeruginosa pathogenicity. P. aeruginosa genome encodes at least 38 TetR-family proteins, and PA3699 is the eighth member of this group functionally characterized so far and the first one shown to bind the lasR promoter in vitro. |
| doi_str_mv | 10.1371/journal.pone.0069554 |
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LasR is a key QS signal receptor since it acts as a global transcriptional regulator required for optimal expression of main virulence factors. P. aeruginosa modulates the QS response by integrating this cell density-dependent circuit to environmental and metabolic cues. Hence, QS also controls the adaptation to challenging environmental niches, such as infection sites. However, little is known about the molecular mechanisms connecting QS and other signalling pathways. In this work, DNA-affinity chromatography was used to identify new lasR transcriptional regulators. This approach led to the identification and functional characterization of the TetR-like transcriptional repressor PA3699. This protein was purified and shown to directly bind to the lasR promoter region in vitro. The induction of PA3699 expression in P. aeruginosa PAO1 cultures repressed lasR promoter activity and the production of LasR-dependent virulence factors, such as elastase, pyocyanin, and proteases. These findings suggest a role for PA3699 in P. aeruginosa pathogenicity. P. aeruginosa genome encodes at least 38 TetR-family proteins, and PA3699 is the eighth member of this group functionally characterized so far and the first one shown to bind the lasR promoter in vitro.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0069554</identifier><identifier>PMID: 23861975</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Affinity chromatography ; Antibiotics ; Bacterial Proteins - genetics ; Biofilms ; Cell density ; Chromatography ; Cross infection ; Cues ; Deoxyribonucleic acid ; DNA ; Elastase ; Gene Expression Regulation, Bacterial ; Genes ; Genetic aspects ; Genomes ; Health aspects ; Laboratories ; Mass spectrometry ; Metabolism ; Molecular modelling ; Nosocomial infections ; Pathogenicity ; Pathogens ; Promoter Regions, Genetic ; Protein Binding ; Proteins ; Pseudomonas aeruginosa ; Pseudomonas aeruginosa - genetics ; Pseudomonas aeruginosa - metabolism ; Pyocyanin ; Quorum Sensing - genetics ; Regulation ; Repressor Proteins - metabolism ; Scientific imaging ; Signal transduction ; Signaling ; Trans-Activators - genetics ; Transcription ; Transcription (Genetics) ; Transcription, Genetic ; Virulence ; Virulence factors ; Virulence Factors - genetics</subject><ispartof>PloS one, 2013-07, Vol.8 (7), p.e69554</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Longo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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LasR is a key QS signal receptor since it acts as a global transcriptional regulator required for optimal expression of main virulence factors. P. aeruginosa modulates the QS response by integrating this cell density-dependent circuit to environmental and metabolic cues. Hence, QS also controls the adaptation to challenging environmental niches, such as infection sites. However, little is known about the molecular mechanisms connecting QS and other signalling pathways. In this work, DNA-affinity chromatography was used to identify new lasR transcriptional regulators. This approach led to the identification and functional characterization of the TetR-like transcriptional repressor PA3699. This protein was purified and shown to directly bind to the lasR promoter region in vitro. The induction of PA3699 expression in P. aeruginosa PAO1 cultures repressed lasR promoter activity and the production of LasR-dependent virulence factors, such as elastase, pyocyanin, and proteases. These findings suggest a role for PA3699 in P. aeruginosa pathogenicity. P. aeruginosa genome encodes at least 38 TetR-family proteins, and PA3699 is the eighth member of this group functionally characterized so far and the first one shown to bind the lasR promoter in vitro.</description><subject>Affinity chromatography</subject><subject>Antibiotics</subject><subject>Bacterial Proteins - genetics</subject><subject>Biofilms</subject><subject>Cell density</subject><subject>Chromatography</subject><subject>Cross infection</subject><subject>Cues</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Elastase</subject><subject>Gene Expression Regulation, Bacterial</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genomes</subject><subject>Health aspects</subject><subject>Laboratories</subject><subject>Mass spectrometry</subject><subject>Metabolism</subject><subject>Molecular modelling</subject><subject>Nosocomial infections</subject><subject>Pathogenicity</subject><subject>Pathogens</subject><subject>Promoter Regions, Genetic</subject><subject>Protein Binding</subject><subject>Proteins</subject><subject>Pseudomonas aeruginosa</subject><subject>Pseudomonas aeruginosa - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Longo, Francesca</au><au>Rampioni, Giordano</au><au>Bondì, Roslen</au><au>Imperi, Francesco</au><au>Fimia, Gian Maria</au><au>Visca, Paolo</au><au>Zennaro, Elisabetta</au><au>Leoni, Livia</au><au>Coenye, Tom</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A new transcriptional repressor of the pseudomonas aeruginosa quorum sensing receptor gene lasR</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-07-05</date><risdate>2013</risdate><volume>8</volume><issue>7</issue><spage>e69554</spage><pages>e69554-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Pseudomonas aeruginosa pathogenic potential is controlled via multiple regulatory pathways, including three quorum sensing (QS) systems. LasR is a key QS signal receptor since it acts as a global transcriptional regulator required for optimal expression of main virulence factors. P. aeruginosa modulates the QS response by integrating this cell density-dependent circuit to environmental and metabolic cues. Hence, QS also controls the adaptation to challenging environmental niches, such as infection sites. However, little is known about the molecular mechanisms connecting QS and other signalling pathways. In this work, DNA-affinity chromatography was used to identify new lasR transcriptional regulators. This approach led to the identification and functional characterization of the TetR-like transcriptional repressor PA3699. This protein was purified and shown to directly bind to the lasR promoter region in vitro. The induction of PA3699 expression in P. aeruginosa PAO1 cultures repressed lasR promoter activity and the production of LasR-dependent virulence factors, such as elastase, pyocyanin, and proteases. These findings suggest a role for PA3699 in P. aeruginosa pathogenicity. P. aeruginosa genome encodes at least 38 TetR-family proteins, and PA3699 is the eighth member of this group functionally characterized so far and the first one shown to bind the lasR promoter in vitro.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23861975</pmid><doi>10.1371/journal.pone.0069554</doi><tpages>e69554</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Affinity chromatography Antibiotics Bacterial Proteins - genetics Biofilms Cell density Chromatography Cross infection Cues Deoxyribonucleic acid DNA Elastase Gene Expression Regulation, Bacterial Genes Genetic aspects Genomes Health aspects Laboratories Mass spectrometry Metabolism Molecular modelling Nosocomial infections Pathogenicity Pathogens Promoter Regions, Genetic Protein Binding Proteins Pseudomonas aeruginosa Pseudomonas aeruginosa - genetics Pseudomonas aeruginosa - metabolism Pyocyanin Quorum Sensing - genetics Regulation Repressor Proteins - metabolism Scientific imaging Signal transduction Signaling Trans-Activators - genetics Transcription Transcription (Genetics) Transcription, Genetic Virulence Virulence factors Virulence Factors - genetics |
| title | A new transcriptional repressor of the pseudomonas aeruginosa quorum sensing receptor gene lasR |
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