Identification of Synthetic Inducers and Inhibitors of the Quorum-Sensing Regulator LasR in Pseudomonas aeruginosa by High-Throughput Screening

被引：47
作者：
Borlee, Bradley R. [1 ]
Geske, Grant D. [3 ]
Blackwell, Helen E. [3 ]
Handelsman, Jo [1 ,2 ]
机构：
[1] Univ Wisconsin, Dept Plant Pathol, Madison, WI 53706 USA
[2] Univ Wisconsin, Dept Bacteriol, Madison, WI 53706 USA
[3] Univ Wisconsin, Dept Chem, Madison, WI 53706 USA
来源：
APPLIED AND ENVIRONMENTAL MICROBIOLOGY | 2010年 / 76卷 / 24期
关键词：
CELL COMMUNICATION; GENE-EXPRESSION; VIRULENCE; BACTERIA;
D O I：
10.1128/AEM.00499-10
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
We report the screening of 16,000 synthetic compounds for induction and inhibition of quorum sensing in a Pseudomonas putida N-acylated L-homoserine lactone (AHL) sensor strain engineered with the LasR transcriptional activator. LasR controls virulence gene expression in the opportunistic pathogen Pseudomonas aeruginosa and is of significant interest as a therapeutic target. Nine compounds that inhibit and 14 compounds that induce LasR activity were identified in our high-throughput screen.
引用
收藏
页码：8255 / 8258
页数：4
相关论文
共 15 条
[1]   gfp-based N-acyl homoserine-lactone sensor systems for detection of bacterial communication [J].
Andersen, JB ;
Heydorn, A ;
Hentzer, M ;
Eberl, L ;
Geisenberger, O ;
Christensen, BB ;
Molin, S ;
Givskov, M .
APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 2001, 67 (02) :575-585
[2]   Molecular insights into quorum sensing in the human pathogen Pseudomonas aeruginosa from the structure of the virulence regulator LasR bound to its autoinducer [J].
Bottomley, Matthew J. ;
Muraglia, Ester ;
Bazzo, Renzo ;
Carfi, Andrea .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (18) :13592-13600
[3]   Regulation of gene expression by cell-to-cell communication: Acyl-homoserine lactone quorum sensing [J].
Fuqua, C ;
Parsek, MR ;
Greenberg, EP .
ANNUAL REVIEW OF GENETICS, 2001, 35 :439-468
[4]   Expanding dialogues: from natural autoinducers to non-natural analogues that modulate quorum sensing in Gram-negative bacteria [J].
Geske, Grant D. ;
O'Neill, Jennifer C. ;
Blackwell, Helen E. .
CHEMICAL SOCIETY REVIEWS, 2008, 37 (07) :1432-1447
[5]  
Hentzer M, 2003, J CLIN INVEST, V112, P1300, DOI 10.1172/JCI20074
[6]   Role of the quorum-sensing system in experimental pneumonia due to Pseudomonas aeruginosa in rats [J].
Lesprit, P ;
Faurisson, F ;
Join-Lambert, O ;
Roudot-Thoraval, F ;
Foglino, M ;
Vissuzaine, C ;
Carbon, C .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2003, 167 (11) :1478-1482
[7]   A structurally unrelated mimic of a Pseudomonas aeruginosa acyl-homoserine lactone quorum-sensing signal [J].
Muh, Ute ;
Hare, Brian J. ;
Duerkop, Breck A. ;
Schuster, Martin ;
Hanzelka, Brian L. ;
Heim, Roger ;
Olson, Eric R. ;
Greenberg, E. Peter .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (45) :16948-16952
[8]   Novel Pseudomonas aeruginosa quorum-sensing inhibitors identified in an ultra-high-throughput screen [J].
Muh, Ute ;
Schuster, Martin ;
Heim, Roger ;
Singh, Ashvani ;
Olson, Eric R. ;
Greenberg, E. Peter .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2006, 50 (11) :3674-3679
[9]   Inhibitors and Antagonists of Bacterial Quorum Sensing [J].
Ni, Nanting ;
Li, Minyong ;
Wang, Junfeng ;
Wang, Binghe .
MEDICINAL RESEARCH REVIEWS, 2009, 29 (01) :65-124
[10]   Pseudomonas aeruginosa cell-to-cell signaling is required for virulence in a model of acute pulmonary infection [J].
Pearson, JP ;
Feldman, M ;
Iglewski, BH ;
Prince, A .
INFECTION AND IMMUNITY, 2000, 68 (07) :4331-4334
12