Discovery of antagonists of PqsR, a key player in 2-alkyl-4-quinolone-dependent quorum sensing in Pseudomonas aeruginosa.
Name:
Publisher version
View Source
Access full-text PDFOpen Access
View Source
Check access options
Check access options
Average rating
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Star rating
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Authors
Lu, CenbinKirsch, Benjamin
Zimmer, Christina
de Jong, Johannes C
Henn, Claudia
Maurer, Christine K
Müsken, Mathias
Häussler, Susanne
Steinbach, Anke
Hartmann, Rolf W
Issue Date
2012-03-23
Metadata
Show full item recordAbstract
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.Citation
Discovery of antagonists of PqsR, a key player in 2-alkyl-4-quinolone-dependent quorum sensing in Pseudomonas aeruginosa. 2012, 19 (3):381-90 Chem. Biol.Affiliation
Helmholtz Institute for Pharmaceutical Research Saarland, Campus C2.3, 66123 Saarbrücken, Germany.Journal
Chemistry & biologyPubMed ID
22444593Type
ArticleLanguage
enISSN
1879-1301ae974a485f413a2113503eed53cd6c53
10.1016/j.chembiol.2012.01.015
Scopus Count
The following license files are associated with this item:
Related articles
- Identification of small-molecule antagonists of the Pseudomonas aeruginosa transcriptional regulator PqsR: biophysically guided hit discovery and optimization.
- Authors: Klein T, Henn C, de Jong JC, Zimmer C, Kirsch B, Maurer CK, Pistorius D, Müller R, Steinbach A, Hartmann RW
- Issue date: 2012 Sep 21
- Quorum sensing by 2-alkyl-4-quinolones in Pseudomonas aeruginosa and other bacterial species.
- Authors: Dubern JF, Diggle SP
- Issue date: 2008 Sep
- Structural basis for native agonist and synthetic inhibitor recognition by the Pseudomonas aeruginosa quorum sensing regulator PqsR (MvfR).
- Authors: Ilangovan A, Fletcher M, Rampioni G, Pustelny C, Rumbaugh K, Heeb S, Cámara M, Truman A, Chhabra SR, Emsley J, Williams P
- Issue date: 2013
- Discovery and biophysical characterization of 2-amino-oxadiazoles as novel antagonists of PqsR, an important regulator of Pseudomonas aeruginosa virulence.
- Authors: Zender M, Klein T, Henn C, Kirsch B, Maurer CK, Kail D, Ritter C, Dolezal O, Steinbach A, Hartmann RW
- Issue date: 2013 Sep 12
- PqsR-independent quorum-sensing response of Pseudomonas aeruginosa ATCC 9027 outlier-strain reveals new insights on the PqsE effect on RhlR activity.
- Authors: García-Reyes S, Cocotl-Yañez M, Soto-Aceves MP, González-Valdez A, Servín-González L, Soberón-Chávez G
- Issue date: 2021 Oct