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

Thomas Bovbjerg Rasmussen, Thomas Bjarnsholt, Mette Elena Skindersoe, Morten Hentzer, Peter Kristoffersen, Manuela Köte, John Nielsen, Leo Eberl, Michael Givskov

536 Citationer (Scopus)

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.

OriginalsprogEngelsk
TidsskriftJournal of Bacteriology
Vol/bind187
Udgave nummer5
Sider (fra-til)1799-814
Antal sider16
ISSN0021-9193
DOI
StatusUdgivet - mar. 2005
Udgivet eksterntJa

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