Quinolone signaling in the cell-to-cell communication system of Pseudomonas aeruginosa

Numerous species of bacteria use an elegant regulatory mechanism known as q uorum sensing to control the,expression of specific genes in a cell-density dependent manner. In Gram-negative bacteria, quorum sensing systems functi on through a cell-to-cell signal molecule (autoinducer) that consists of a homoserine lactone with a fatty acid side chain. Such is the case in the op portunistic human pathogen Pseudomonas aeruginosa, which contains two quoru m sensing systems (las and rhl) that operate via the autoinducers, N-(3-oxo dodecanoyl)-L-homoserine lactone and N-butyryl-L-homoserine lactone, The st udy of these signal molecules has shown that they bind to and activate tran scriptional activator proteins that specifically induce numerous P. aerugin osa virulence genes. We report here that P. aeruginosa produces ano ther si gnal molecule, 2-heptyl-3-hydroxy-4-quinolone, which has been designated as the Pseudomonas quinolone signal. It was found that this unique cell-to-ce ll signal controlled the expression of lasB, which encodes for the major vi rulence factor, LasB elastase, We also show that the synthesis and bioactiv ity of Pseudomonas quinolone signal were mediated by the P. aeruginosa las and rhl quorum sensing systems, respectively. The demonstration that 2-hept yl-3-hydroxy-4-quinolone can function as an intercellular signal sheds ligh t on the role of secondary metabolites and shows that P. aeruginosa cell-to -cell signaling is not restricted to acyl-homoserine lactones.