title: Screening for quorum-sensing inhibitors (QSI) by use of a novel genetic system, the QSI selector.
abstract: 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.
authors.affiliation: Center for Biomedical Microbiology, BioCentrum-DTU, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.
authors.forename: Thomas Bovbjerg
authors.initials: TB
authors.lastname: Rasmussen
authors.forename: Thomas
authors.initials: T
authors.lastname: Bjarnsholt
authors.forename: Mette Elena
authors.initials: ME
authors.lastname: Skindersoe
authors.forename: Morten
authors.initials: M
authors.lastname: Hentzer
authors.forename: Peter
authors.initials: P
authors.lastname: Kristoffersen
authors.forename: Manuela
authors.initials: M
authors.lastname: Köte
authors.forename: John
authors.initials: J
authors.lastname: Nielsen
authors.forename: Leo
authors.initials: L
authors.lastname: Eberl
authors.forename: Michael
authors.initials: M
authors.lastname: Givskov
mesh_terms: 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*
chemical_list: D000900:Anti-Bacterial Agents; D010936:Plant Extracts; C088386:homoserine lactone; D015107:4-Butyrolactone
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