Covalent Inhibition of Bacterial Quorum Sensing

被引：161

作者：

Amara, Neri ^{[1
,3
]}

Mashiach, Roi ^{[1
,3
]}

Amar, Dotan ^{[2
,3
]}

Krief, Pnina ^{[1
,3
]}

Spieser, Stephane A. H. ^{[4
]}

Bottomley, Matthew J. ^{[4
]}

Aharoni, Amir ^{[2
,3
]}

Meijler, Michael M. ^{[1
,3
]}

机构：

[1] Ben Gurion Univ Negev, Dept Chem, IL-84105 Beer Sheva, Israel

[2] Ben Gurion Univ Negev, Dept Life Sci, IL-84105 Beer Sheva, Israel

[3] Ben Gurion Univ Negev, Natl Inst Biotechnol Negev, IL-84105 Beer Sheva, Israel

[4] Ist Ric Biol Mol P Angeletti, Rome, Italy

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2009年 / 131卷 / 30期

关键词：

PSEUDOMONAS-AERUGINOSA VIRULENCE; SMALL-MOLECULE INHIBITORS; CHEMICAL COMMUNICATION; SYNTHETIC LIGANDS; ANALOGS; PROBES; MECHANISMS; EXPRESSION; STRATEGIES; REGULATOR;

D O I：

10.1021/ja903292v

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Chemical coordination of gene expression among bacteria as a function of population density is regulated by a mechanism known as 'quorum sensing' (OS). QS in Pseudomonas aeruginosa, an opportunistic pathogen that causes disease in immunocompromised patients, is mediated by binding of the transcriptional activator, LasR, to its ligand, 3-oxo-C-12-HSL, leading to population-wide secretion of virulence factors and biofilm formation. We have targeted QS in P. aeruginosa with a set of electrophilic probes designed to covalently bind Cys79 in the LasR binding pocket, leading to specific inhibition of QS-regulated gene expression and concomitant reduction of virulence factor secretion and biofilm formation. This first example of covalent modification of a QS receptor provides a new tool to study molecular mechanisms of bacterial group behavior and could lead to new strategies for targeting bacterial virulence.

引用

页码：10610 / 10619

页数：10

共 53 条

[1] Identification of proteases that regulate erythrocyte rupture by the malaria parasite Plasmodium falciparum [J].