Discovery of Antagonists of PqsR, a Key Player in 2-Alkyl-4-quinolone-Dependent Quorum Sensing in Pseudomonas aeruginosa
| Autor: | Claudia Henn, Benjamin Kirsch, Johannes C. de Jong, Christina Zimmer, Cenbin Lu, Christine K. Maurer, Susanne Häussler, Anke Steinbach, Rolf W. Hartmann, Mathias Müsken |
|---|---|
| Přispěvatelé: | Helmholtz Institute for Pharmaceutical Research Saarland, Campus C2.3, 66123 Saarbrücken, Germany. |
| Rok vydání: | 2012 |
| Předmět: |
Clinical Biochemistry
Biology medicine.disease_cause Biochemistry Virulence factor Microbiology chemistry.chemical_compound Pyocyanin Bacterial Proteins Genes Reporter Drug Discovery medicine Molecular Biology Escherichia coli Pharmacology Reporter gene 4-Quinolones Pseudomonas aeruginosa Biofilm Quorum Sensing General Medicine Ligand (biochemistry) Kinetics Quorum sensing chemistry Drug Design Pyocyanine Molecular Medicine |
| Zdroj: | Chemistry & Biology. 19:381-390 |
| ISSN: | 1074-5521 |
| Popis: | Summary The pqs quorum sensing communication system of Pseudomonas aeruginosa controls virulence factor production and is involved in biofilm formation, therefore playing an important role for pathogenicity. In order to attenuate P. aeruginosa pathogenicity, we followed a ligand-based drug design approach and synthesized a series of compounds targeting PqsR, the receptor of the pqs system. In vitro evaluation using a reporter gene assay in Escherichia coli led to the discovery of the first competitive PqsR antagonists, which are highly potent (K d,app of compound 20: 7 nM). These antagonists are able to reduce the production of the virulence factor pyocyanin in P. aeruginosa . Our finding offers insights into the ligand-receptor interaction of PqsR and provides a promising starting point for further drug design. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|