Overcoming the unexpected functional inversion of a PqsR antagonist in Pseudomonas aeruginosa: an in vivo potent antivirulence agent targeting pqs quorum sensing.

Lu, Cenbin; Maurer, Christine K; Kirsch, Benjamin; Steinbach, Anke; Hartmann, Rolf W

dc.contributor.author	Lu, Cenbin
dc.contributor.author	Maurer, Christine K
dc.contributor.author	Kirsch, Benjamin
dc.contributor.author	Steinbach, Anke
dc.contributor.author	Hartmann, Rolf W
dc.date.accessioned	2014-05-12T09:42:12Z
dc.date.available	2014-05-12T09:42:12Z
dc.date.issued	2014-01-20
dc.identifier.citation	Overcoming 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.	en
dc.identifier.issn	1521-3773
dc.identifier.pmid	24338917
dc.identifier.doi	10.1002/anie.201307547
dc.identifier.uri	http://hdl.handle.net/10033/316718
dc.description.abstract	The 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.
dc.language.iso	en	en
dc.rights	Archived with thanks to Angewandte Chemie (International ed. in English)	en
dc.title	Overcoming the unexpected functional inversion of a PqsR antagonist in Pseudomonas aeruginosa: an in vivo potent antivirulence agent targeting pqs quorum sensing.	en
dc.type	Article	en
dc.contributor.department	Division of Drug design and optimization. Helmholtz-Institute for Pharmaceutical Research Saarland & Pharmaceutical and Medicinal Chemistry, Saarland University.	en
dc.identifier.journal	Angewandte Chemie (International ed. in English)	en
refterms.dateFOA	2015-01-15T00:00:00Z
html.description.abstract	The 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.