Article: article from journal or magazin.
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.
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.
4-Butyrolactone/analogs & derivatives, 4-Butyrolactone/metabolism, Amino Acid Sequence, Bacterial Proteins/genetics, Bacterial Proteins/metabolism, Chromosome Mapping, Cloning, Molecular, Cyanides/metabolism, DNA-Binding Proteins/genetics, DNA-Binding Proteins/metabolism, Gene Expression Regulation, Bacterial, Lipase/biosynthesis, Molecular Sequence Data, Plasmids, Pseudomonas aeruginosa/genetics, Pseudomonas aeruginosa/metabolism, Pyocyanine/metabolism, Sequence Alignment, Signal Transduction/genetics, Trans-Activators/genetics, Trans-Activators/metabolism, Transcription, Genetic
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