Acyl homoserine-lactone quorum-sensing signal generation

Acyl homoserine lactones (acyl-HSLs) are important intercellular signaling molecules used by many bacteria to monitor their population density in quor um-sensing control of gene expression. These signals are synthesized by mem bers of the LuxI family of proteins, To understand the mechanism of acyl-HS L synthesis we have purified the Pseudomonas aeruginosa RhlI protein and an alyzed the kinetics of acyl-HSL synthesis by this enzyme, Purified RhlI cat alyzes the synthesis of acyl-HSLs from acyl-acyl carrier proteins and S-ade nosylmethionine. An analysis of the patterns of product inhibition indicate d that RhlI catalyzes signal synthesis by a sequential, ordered reaction me chanism in which S-adenosylmethionine binds to RhlI as the initial step in the enzymatic mechanism. Because pathogenic bacteria such as P. aeruginosa use acyl-HSL signals to regulate virulence genes, an understanding of the m echanism of signal synthesis and identification of inhibitors of signal syn thesis has implications for development of quorum sensing-targeted antiviru lence molecules.