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

• Published in: Molecular microbiology 1997-04, Vol.24 (2), p.309-319
• Main Authors: Reimmann, Cornelia, Beyeler, Markus, Latifi, Amel, Winteler, Harald, Foglino, Maryline, Lazdunski, Andrée, Haas, Dieter
• Format: Article
• Language: English
• Subjects: 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; Pseudomonas aeruginosa - genetics; Pseudomonas aeruginosa - metabolism; Pyocyanine - metabolism; Sequence Alignment; Signal Transduction - genetics; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription, Genetic
• ISSN: 0950-382X; 1365-2958
• DOI: 10.1046/j.1365-2958.1997.3291701.x

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 RhlR (VsmR), and of the transcriptional activator LasR, which is known to positively regulate RhlR expression. Amplification of gacA on a multicopy plasmid caused precocious and enhanced production of BHL, RhlR and LasR. In parallel, the gacA gene dosage markedly influenced the BHL/RhlR‐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 RhlR in the complex, cell‐density‐dependent signal‐transduction pathway regulating several exoproducts and virulence factors of P. aeruginosa via BHL.