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

Mol Microbiol. 1997 Apr;24(2):309-19. 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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • Bacterial Proteins
  • Cyanides
  • DNA-Binding Proteins
  • GacA protein, Bacteria
  • LasR protein, Pseudomonas aeruginosa
  • N-butyrylhomoserine lactone
  • Trans-Activators
  • rhiR protein, Rhizobium leguminosarum
  • Pyocyanine
  • Lipase
  • 4-Butyrolactone

Associated data

  • GENBANK/U89528