title: Synthetic ligands that activate and inhibit a quorum-sensing regulator in Pseudomonas aeruginosa.
abstract: The transcription factor QscR is a regulator of quorum sensing in Pseudomonas aeruginosa and plays a role in controlling virulence in this prevalent opportunistic pathogen. This study outlines the discovery of a set of synthetic N-acylated homoserine lactones that are capable of either activating or strongly inhibiting QscR in a cell-based reporter gene assay. We demonstrate that the synthetic antagonists inhibit ligand-dependent QscR binding to DNA. Several of these ligands can selectively modulate QscR instead of LasR, or modulate the activity of both receptors, and represent new chemical tools to study the hierarchy of quorum-sensing signaling in P. aeruginosa.
authors: Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706-1322, USA.
authors: Margrith E
authors: ME
authors: Mattmann
authors: Grant D
authors: GD
authors: Geske
authors: Gregory A
authors: GA
authors: Worzalla
authors: Josephine R
authors: JR
authors: Chandler
authors: Kaia J
authors: KJ
authors: Sappington
authors: E Peter
authors: EP
authors: Greenberg
authors: Helen E
authors: HE
authors: Blackwell
mesh_terms: D054742:Acyl-Butyrolactones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001426:Bacterial Proteins / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004269:DNA, Bacterial / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D008024:Ligands; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000378:metabolism; D012097:Repressor Proteins / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D037521:Virulence Factors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D054742:Acyl-Butyrolactones; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D008024:Ligands; C434259:QscR protein, Pseudomonas aeruginosa; D012097:Repressor Proteins; D037521:Virulence Factors