Screening for quorum-sensing inhibitors (QSI) by use of a novel genetic system, the QSI selector.
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.
Rasmussen
Thomas Bovbjerg
TB
Center for Biomedical Microbiology, BioCentrum-DTU, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.
Bjarnsholt
Thomas
T
Skindersoe
Mette Elena
ME
Hentzer
Morten
M
Kristoffersen
Peter
P
Köte
Manuela
M
Nielsen
John
J
Eberl
Leo
L
Givskov
Michael
M
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects; D017173:Caenorhabditis elegans; D003198:Computer Simulation; D015536:Down-Regulation; D024881:Drug Resistance, Bacterial; D005737:Garlic; D008826:Microbial Sensitivity Tests / Q000379:methods*; D010936:Plant Extracts / Q000494:pharmacology; D010946:Plants, Medicinal; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*
D000900:Anti-Bacterial Agents; D010936:Plant Extracts; C088386:homoserine lactone; D015107:4-Butyrolactone
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