Overcoming the unexpected functional inversion of a PqsR antagonist in Pseudomonas aeruginosa: an in vivo potent antivirulence agent targeting pqs quorum sensing.
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.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractThe virulence regulator PqsR of Pseudomonas aeruginosa is considered as an attractive target for attenuating the bacterial pathogenicity without eliciting resistance. However, despite efforts and desires, no promising PqsR antagonist has been discovered thus far. Now, a surprising functionality change of a highly affine PqsR antagonist in P. aeruginosa is revealed, which is mediated by a bacterial signal molecule synthase and responsible for low cellular potency. Blockade of the susceptible position led to the discovery of the first antivirulence compound that is potent in vivo and targets PqsR, thus providing a proof of concept for this novel antivirulence therapy.
CitationOvercoming the unexpected functional inversion of a PqsR antagonist in Pseudomonas aeruginosa: an in vivo potent antivirulence agent targeting pqs quorum sensing. 2014, 53 (4):1109-12 Angew. Chem. Int. Ed. Engl.
AffiliationDivision of Drug design and optimization. Helmholtz-Institute for Pharmaceutical Research Saarland & Pharmaceutical and Medicinal Chemistry, Saarland University.
The following license files are associated with this item:
- 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
- Optimization of anti-virulence PqsR antagonists regarding aqueous solubility and biological properties resulting in new insights in structure-activity relationships.
- Authors: Lu C, Kirsch B, Maurer CK, de Jong JC, Braunshausen A, Steinbach A, Hartmann RW
- Issue date: 2014 May 22
- Discovery of antagonists of PqsR, a key player in 2-alkyl-4-quinolone-dependent quorum sensing in Pseudomonas aeruginosa.
- Authors: Lu C, Kirsch B, Zimmer C, de Jong JC, Henn C, Maurer CK, Müsken M, Häussler S, Steinbach A, Hartmann RW
- Issue date: 2012 Mar 23
- Application of Dual Inhibition Concept within Looped Autoregulatory Systems toward Antivirulence Agents against Pseudomonas aeruginosa Infections.
- Authors: Thomann A, de Mello Martins AG, Brengel C, Empting M, Hartmann RW
- Issue date: 2016 May 20
- Novel quinazolinone inhibitors of the Pseudomonas aeruginosa quorum sensing transcriptional regulator PqsR.
- Authors: Grossman S, Soukarieh F, Richardson W, Liu R, Mashabi A, Emsley J, Williams P, Cámara M, Stocks MJ
- Issue date: 2020 Dec 15