TY - JOUR
T1 - Screening for quorum-sensing inhibitors (QSI) by use of a novel genetic system, the QSI selector
AU - Rasmussen, Thomas Bovbjerg
AU - Bjarnsholt, Thomas
AU - Skindersoe, Mette Elena
AU - Hentzer, Morten
AU - Kristoffersen, Peter
AU - Köte, Manuela
AU - Nielsen, John
AU - Eberl, Leo
AU - Givskov, Michael
N1 - Keywords: 4-Butyrolactone; Animals; Anti-Bacterial Agents; Biofilms; Caenorhabditis elegans; Computer Simulation; Down-Regulation; Drug Resistance, Bacterial; Garlic; Microbial Sensitivity Tests; Plant Extracts; Plants, Medicinal; Pseudomonas aeruginosa
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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.
U2 - 10.1128/JB.187.5.1799-1814.2005
DO - 10.1128/JB.187.5.1799-1814.2005
M3 - Journal article
C2 - 15716452
SN - 0021-9193
VL - 187
SP - 1799
EP - 1814
JO - Journal of Bacteriology
JF - Journal of Bacteriology
IS - 5
ER -