Overcoming the unexpected functional inversion of a PqsR antagonist in Pseudomonas aeruginosa: an in vivo potent antivirulence agent targeting pqs quorum sensing.
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Issue Date
2014-01-20
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Show full item recordAbstract
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.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.Affiliation
Division of Drug design and optimization. Helmholtz-Institute for Pharmaceutical Research Saarland & Pharmaceutical and Medicinal Chemistry, Saarland University.PubMed ID
24338917Type
ArticleLanguage
enISSN
1521-3773ae974a485f413a2113503eed53cd6c53
10.1002/anie.201307547
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