Overcoming the Unexpected Functional Inversion of a PqsR Antagonist in Pseudomonas aeruginosa: An In Vivo Potent Antivirulence Agent Targeting pqs Quorum Sensing

被引：71

作者：

Lu, Cenbin ^{[1
,2
]}

Maurer, Christine K. ^{[1
,2
]}

Kirsch, Benjamin ^{[1
,2
]}

Steinbach, Anke ^{[1
,2
]}

Hartmann, Rolf W. ^{[1
,2
]}

机构：

[1] Helmholtz Inst Pharmaceut Res Saarland, D-66123 Saarbrucken, Germany

[2] Univ Saarland, D-66123 Saarbrucken, Germany

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2014年 / 53卷 / 04期

关键词：

antivirulence; drug discovery; inhibitors; medicinal chemistry; resistance; QUINOLONE SIGNAL; VIRULENCE; PATHOGENESIS; VALIDATION; INHIBITORS; MVFR;

D O I：

10.1002/anie.201307547

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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 invivo and targets PqsR, thus providing a proof of concept for this novel antivirulence therapy.

引用

页码：1109 / 1112

页数：4

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