title: The phenazine pyocyanin is a terminal signalling factor in the quorum sensing network of Pseudomonas aeruginosa.
abstract: Certain members of the fluorescent pseudomonads produce and secrete phenazines. These heterocyclic, redox-active compounds are toxic to competing organisms, and the cause of these antibiotic effects has been the focus of intense research efforts. It is largely unknown, however, how pseudomonads themselves respond to - and survive in the presence of - these compounds. Using Pseudomonas aeruginosa DNA microarrays and quantitative RT-PCR, we demonstrate that the phenazine pyocyanin elicits the upregulation of genes/operons that function in transport [such as the resistance-nodulation-cell division (RND) efflux pump MexGHI-OpmD] and possibly in redox control (such as PA2274, a putative flavin-dependant monooxygenase), and downregulates genes involved in ferric iron acquisition. Strikingly, mexGHI-opmD and PA2274 were previously shown to be regulated by the PA14 quorum sensing network that controls the production of virulence factors (including phenazines). Through mutational analysis, we show that pyocyanin is the physiological signal for the upregulation of these quorum sensing-controlled genes during stationary phase and that the response is mediated by the transcription factor SoxR. Our results implicate phenazines as signalling molecules in both P. aeruginosa PA14 and PAO1.
authors.affiliation: Divisions of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Lars E P
authors.initials: LE
authors.lastname: Dietrich
authors.forename: Alexa
authors.initials: A
authors.lastname: Price-Whelan
authors.forename: Ashley
authors.initials: A
authors.lastname: Petersen
authors.forename: Marvin
authors.initials: M
authors.lastname: Whiteley
authors.forename: Dianne K
authors.initials: DK
authors.lastname: Newman
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D005798:Genes, Bacterial / Q000235:genetics; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D009876:Operon / Q000235:genetics; D010619:Phenazines / Q000378:metabolism* / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D011710:Pyocyanine / Q000378:metabolism* / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D010619:Phenazines; D014157:Transcription Factors; C070724:SoxR protein, Bacteria; D011710:Pyocyanine