Screening for quorum-sensing inhibitors (QSI) by use of a novel genetic system, the QSI selector

被引:446
作者
Rasmussen, TB
Bjarnsholt, T
Skindersoe, ME
Hentzer, M
Kristoffersen, P
Köte, M
Nielsen, J
Eberl, L
Givskov, M [1 ]
机构
[1] Tech Univ Denmark, Bioctr, Ctr Biomed Microbiol, DK-2800 Lyngby, Denmark
[2] Carlsberg Res Ctr, Biosector, Valby, Denmark
[3] Royal Vet & Agr Univ, Dept Chem, DK-1871 Frederiksberg, Denmark
[4] Tech Univ Munich, Lehrstuhl Mikrobiol, D-8050 Freising Weihenstephan, Germany
[5] Univ Zurich, Dept Microbiol, Zurich, Switzerland
关键词
D O I
10.1128/JB.187.5.1799-1814.2005
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
With the widespread appearance of antibiotic-resistant bacteria, there is an increasing demand for novel strategies to control infectious diseases. Furthermore, it has become apparent that the bacterial life style also contributes significantly to this problem. Bacteria living in the biofilm mode of growth tolerate conventional antimicrobial treatments. The discovery that many bacteria use quorum-sensing (QS) systems to coordinate virulence and biofilm development has pointed out a new, promising target for antimicrobial drugs. We constructed a collection of screening systems, QS inhibitor (QSI) selectors, which enabled us to identify a number of novel QSIs among natural and synthetic compound libraries. The two most active were garlic extract and 4-nitro-pyridine-N-oxide (4-NPO). GeneChip-based transcriptome analysis revealed that garlic extract and 4-NPO had specificity for QS-controlled virulence genes in Pseudomonas aeruginosa. These two QSIs also significantly reduced P. aeruginosa biofilm tolerance to tobramycin treatment as well as virulence in a Caenorhabditis elegans pathogenesis model.
引用
收藏
页码:1799 / 1814
页数:16
相关论文
共 48 条
[1]  
Andersen JB, 1998, APPL ENVIRON MICROB, V64, P2240
[2]   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
[3]   TESTING THE SUSCEPTIBILITY OF BACTERIA IN BIOFILMS TO ANTIBACTERIAL AGENTS [J].
ANWAR, H ;
DASGUPTA, MK ;
COSTERTON, JW .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1990, 34 (11) :2043-2046
[5]   The Ti plasmid of Agrobactetium tumefaciens harbors an attM-paralogous gene, aiiB, also encoding N-acyl homoserine lactonase activity [J].
Carlier, A ;
Uroz, S ;
Smadja, B ;
Fray, R ;
Latour, X ;
Dessaux, Y ;
Faure, D .
APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 2003, 69 (08) :4989-4993
[6]   Quorum-sensing-directed protein expression in Serratia proteamaculans B5a [J].
Christensen, AB ;
Riedel, K ;
Eberl, L ;
Flodgaard, LR ;
Molin, S ;
Gram, L ;
Givskov, M .
MICROBIOLOGY-SGM, 2003, 149 :471-483
[7]  
Clark RA, 2000, J ACQ IMMUN DEF SYND, V23, P99
[8]   A bacterial cell to cell signal in the lungs of cystic fibrosis patients [J].
Collier, DN ;
Anderson, L ;
McKnight, SL ;
Noah, TL ;
Knowles, M ;
Boucher, R ;
Schwab, U ;
Gilligan, P ;
Pesci, EC .
FEMS MICROBIOLOGY LETTERS, 2002, 215 (01) :41-46
[9]   The involvement of cell-to-cell signals in the development of a bacterial biofilm [J].
Davies, DG ;
Parsek, MR ;
Pearson, JP ;
Iglewski, BH ;
Costerton, JW ;
Greenberg, EP .
SCIENCE, 1998, 280 (5361) :295-298
[10]   MINI-TN5 TRANSPOSON DERIVATIVES FOR INSERTION MUTAGENESIS, PROMOTER PROBING, AND CHROMOSOMAL INSERTION OF CLONED DNA IN GRAM-NEGATIVE EUBACTERIA [J].
DELORENZO, V ;
HERRERO, M ;
JAKUBZIK, U ;
TIMMIS, KN .
JOURNAL OF BACTERIOLOGY, 1990, 172 (11) :6568-6572