title: Acyl homoserine-lactone quorum-sensing signal generation.
abstract: Acyl homoserine lactones (acyl-HSLs) are important intercellular signaling molecules used by many bacteria to monitor their population density in quorum-sensing control of gene expression. These signals are synthesized by members of the LuxI family of proteins. To understand the mechanism of acyl-HSL synthesis we have purified the Pseudomonas aeruginosa RhlI protein and analyzed the kinetics of acyl-HSL synthesis by this enzyme. Purified RhlI catalyzes the synthesis of acyl-HSLs from acyl-acyl carrier proteins and S-adenosylmethionine. An analysis of the patterns of product inhibition indicated that RhlI catalyzes signal synthesis by a sequential, ordered reaction mechanism 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 mechanism of signal synthesis and identification of inhibitors of signal synthesis has implications for development of quorum sensing-targeted antivirulence molecules.
authors: Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
authors: M R
authors: MR
authors: Parsek
authors: D L
authors: DL
authors: Val
authors: B L
authors: BL
authors: Hanzelka
authors: J E
authors: JE
authors: Cronan
authors: E P
authors: EP
authors: Greenberg
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000502:physiology; D000213:Acyl Carrier Protein / Q000378:metabolism; D000215:Acylation; D001426:Bacterial Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D008025:Ligases; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012435:S-Adenosylhomocysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D015398:Signal Transduction; D013379:Substrate Specificity; D014157:Transcription Factors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D000213:Acyl Carrier Protein; D001426:Bacterial Proteins; D014157:Transcription Factors; C088386:homoserine lactone; D012435:S-Adenosylhomocysteine; D008025:Ligases; C096955:RHLI protein, Pseudomonas aeruginosa; D015107:4-Butyrolactone