title: The global activator GacA of Pseudomonas aeruginosa PAO positively controls the production of the autoinducer N-butyryl-homoserine lactone and the formation of the virulence factors pyocyanin, cyanide, and lipase.
abstract: The global activator GacA, a highly conserved response regulator in Gram-negative bacteria, is required for the production of exoenzymes and secondary metabolites in Pseudomonas spp. The gacA gene of Pseudomonas aeruginosa PAO1 was isolated and its role in cell-density-dependent gene expression was characterized. Mutational inactivation of gacA resulted in delayed and reduced formation of the cell-density signal N-butyryl-L-homoserine lactone (BHL), of the cognate transcriptional activator RhIR (VsmR), and of the transcriptional activator LasR, which is known to positively regulate RhIR expression. Amplification of gacA on a multicopy plasmid caused precocious and enhanced production of BHL, RhIR and LasR. In parallel, the gacA gene dosage markedly influenced the BHL/RhIR-dependent formation of the cytotoxic compounds pyocyanin and cyanide and the exoenzyme lipase. However, the concentrations of another known cell-density signal of P. aeruginosa, N-oxododecanoyl-L-homoserine lactone, did not always match BHL concentrations. A model accounting for these observations places GacA function upstream of LasR and RhIR in the complex, cell-density-dependent signal-transduction pathway regulating several exoproducts and virulence factors of P. aeruginosa via BHL.
authors.affiliation: Laboratoire de Biologie Microbienne, Université de Lausanne, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Reimmann
authors.forename: M
authors.initials: M
authors.lastname: Beyeler
authors.forename: A
authors.initials: A
authors.lastname: Latifi
authors.forename: H
authors.initials: H
authors.lastname: Winteler
authors.forename: M
authors.initials: M
authors.lastname: Foglino
authors.forename: A
authors.initials: A
authors.lastname: Lazdunski
authors.forename: D
authors.initials: D
authors.lastname: Haas
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000378:metabolism; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003486:Cyanides / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D008049:Lipase / Q000096:biosynthesis; D008969:Molecular Sequence Data; D010957:Plasmids; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000378:metabolism*; D011710:Pyocyanine / Q000378:metabolism*; D016415:Sequence Alignment; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D003486:Cyanides; D004268:DNA-Binding Proteins; C091100:GacA protein, Bacteria; C080365:LasR protein, Pseudomonas aeruginosa; C092312:N-butyrylhomoserine lactone; D015534:Trans-Activators; C074896:rhiR protein, Rhizobium leguminosarum; D011710:Pyocyanine; D008049:Lipase; D015107:4-Butyrolactone