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

2.50
Hdl Handle:
http://hdl.handle.net/10033/316718
Title:
Overcoming the unexpected functional inversion of a PqsR antagonist in Pseudomonas aeruginosa: an in vivo potent antivirulence agent targeting pqs quorum sensing.
Authors:
Lu, Cenbin; Maurer, Christine K; Kirsch, Benjamin; Steinbach, Anke; Hartmann, Rolf W
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.
Affiliation:
Division of Drug design and optimization. Helmholtz-Institute for Pharmaceutical Research Saarland & Pharmaceutical and Medicinal Chemistry, Saarland University.
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.
Journal:
Angewandte Chemie (International ed. in English)
Issue Date:
20-Jan-2014
URI:
http://hdl.handle.net/10033/316718
DOI:
10.1002/anie.201307547
PubMed ID:
24338917
Type:
Article
Language:
en
ISSN:
1521-3773
Appears in Collections:
publications of the department drug design and optimization (HIPS]DDOP)

Full metadata record

DC FieldValue Language
dc.contributor.authorLu, Cenbinen
dc.contributor.authorMaurer, Christine Ken
dc.contributor.authorKirsch, Benjaminen
dc.contributor.authorSteinbach, Ankeen
dc.contributor.authorHartmann, Rolf Wen
dc.date.accessioned2014-05-12T09:42:12Z-
dc.date.available2014-05-12T09:42:12Z-
dc.date.issued2014-01-20-
dc.identifier.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.en
dc.identifier.issn1521-3773-
dc.identifier.pmid24338917-
dc.identifier.doi10.1002/anie.201307547-
dc.identifier.urihttp://hdl.handle.net/10033/316718-
dc.description.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.en
dc.language.isoenen
dc.rightsArchived with thanks to Angewandte Chemie (International ed. in English)en
dc.titleOvercoming the unexpected functional inversion of a PqsR antagonist in Pseudomonas aeruginosa: an in vivo potent antivirulence agent targeting pqs quorum sensing.en
dc.typeArticleen
dc.contributor.departmentDivision of Drug design and optimization. Helmholtz-Institute for Pharmaceutical Research Saarland & Pharmaceutical and Medicinal Chemistry, Saarland University.en
dc.identifier.journalAngewandte Chemie (International ed. in English)en

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