title: The PqsR and RhlR transcriptional regulators determine the level of Pseudomonas quinolone signal synthesis in Pseudomonas aeruginosa by producing two different pqsABCDE mRNA isoforms.
abstract: Regulation of gene expression plays a key role in bacterial adaptability to changes in the environment. An integral part of this gene regulatory network is achieved via quorum sensing (QS) systems that coordinate bacterial responses under high cellular densities. In the nosocomial pathogen Pseudomonas aeruginosa, the 2-alkyl-4-quinolone (pqs) signaling pathway is crucial for bacterial survival under stressful conditions. Biosynthesis of the Pseudomonas quinolone signal (PQS) is dependent on the pqsABCDE operon, which is positively regulated by the LysR family regulator PqsR and repressed by the transcriptional regulator protein RhlR. However, the molecular mechanisms underlying this inhibition have remained elusive. Here, we demonstrate that not only PqsR but also RhlR activates transcription of pqsA. The latter uses an alternative transcriptional start site and induces expression of a longer transcript that forms a secondary structure in the 5' untranslated leader region. As a consequence, access of the ribosome to the Shine-Dalgarno sequence is restricted and translation efficiency reduced. We propose a model of a novel posttranscriptional regulation mechanism that fine-tunes PQS biosynthesis, thus highlighting the complexity of quorum sensing in P. aeruginosa.
authors.affiliation: Department of Molecular Bacteriology, Helmholtz Center for Infection Research, Braunschweig, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Brouwer
authors.affiliation: Department of Molecular Bacteriology, Helmholtz Center for Infection Research, Braunschweig, Germany Institute for Molecular Bacteriology, TWINCORE GmbH, Center of Clinical and Experimental Infection Research, Hannover Medical School and Helmholtz Center for Infection Research, Hannover, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Pustelny
authors.affiliation: Department of Macromolecular Interactions, Helmholtz Center for Infection Research, Braunschweig, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Ritter
authors.affiliation: Microbial Biology, Ruhr University Bochum, Bochum, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Klinkert
authors.affiliation: Microbial Biology, Ruhr University Bochum, Bochum, Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Narberhaus
authors.affiliation: Department of Molecular Bacteriology, Helmholtz Center for Infection Research, Braunschweig, Germany Institute for Molecular Bacteriology, TWINCORE GmbH, Center of Clinical and Experimental Infection Research, Hannover Medical School and Helmholtz Center for Infection Research, Hannover, Germany Susanne.Haeussler@helmholtz-hzi.de.
authors.forename: Susanne
authors.initials: S
authors.lastname: Häussler
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D009876:Operon; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000378:metabolism*; D015363:Quinolones / Q000378:metabolism*; D059368:RNA Isoforms / Q000378:metabolism*
chemical_list: C407944:2-heptyl-3-hydroxy-4-quinolone; D001426:Bacterial Proteins; D015363:Quinolones; D059368:RNA Isoforms; C086515:RhlR protein, Pseudomonas aeruginosa