Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors

Hentzer, Morten, Wu, Hong, Andersen, Jens Bo, Riedel, Kathrin, Rasmussen, Thomas B., Bagge, Niels, Kumar, Naresh, Schembri, Mark A., Song, Zhijun, Kristoffersen, Peter, Manefield, Mike, Costerton, John W., Molin, Søren, Eberl, Leo and Steinberg, Peter (2003) Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. Embo Journal, 22 15: 3803-3815. doi:10.1093/emboj/cdg366


Author Hentzer, Morten
Wu, Hong
Andersen, Jens Bo
Riedel, Kathrin
Rasmussen, Thomas B.
Bagge, Niels
Kumar, Naresh
Schembri, Mark A.
Song, Zhijun
Kristoffersen, Peter
Manefield, Mike
Costerton, John W.
Molin, Søren
Eberl, Leo
Steinberg, Peter
Title Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors
Journal name Embo Journal   Check publisher's open access policy
ISSN 0261-4189
Publication date 2003-08-01
Sub-type Article (original research)
DOI 10.1093/emboj/cdg366
Volume 22
Issue 15
Start page 3803
End page 3815
Total pages 13
Place of publication Oxford
Publisher Nature Publishing
Language eng
Subject 0605 Microbiology
Abstract Traditional treatment of infectious diseases is based on compounds that kill or inhibit growth of bacteria. A major concern with this approach is the frequent development of resistance to antibiotics. The discovery of communication systems (quorum sensing systems) regulating bacterial virulence has afforded a novel opportunity to control infectious bacteria without interfering with growth. Compounds that can override communication signals have been found in the marine environment. Using Pseudomonas aeruginosa PAO1 as an example of an opportunistic human pathogen, we show that a synthetic derivate of natural furanone compounds can act as a potent antagonist of bacterial quorum sensing. We employed GeneChip((R)) microarray technology to identify furanone target genes and to map the quorum sensing regulon. The transcriptome analysis showed that the furanone drug specifically targeted quorum sensing systems and inhibited virulence factor expression. Application of the drug to P.aeruginosa biofilms increased bacterial susceptibility to tobramycin and SDS. In a mouse pulmonary infection model, the drug inhibited quorum sensing of the infecting bacteria and promoted their clearance by the mouse immune response.
Keyword Biochemistry & Molecular Biology
Cell Biology
Antagonists
Biofilm
Furanone
Genechip
Microarray
Quorum Sensing
Alga Delisea-pulchra
N-acylhomoserine Lactones
Gram-negative Bacteria
To-cell Signals
Homoserine-lactone
Secondary Metabolites
Cystic-fibrosis
Halogenated Furanones
Burkholderia-cepacia
Twitching Motility
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown
Additional Notes Authors of this document: Hentzer, M; Wu, H; Andersen, JB; Riedel, K; Rasmussen, TB; Bagge, N; Kumar, N; Schembri, MA; Song, ZJ; Kristoffersen, P; Manefield, M; Costerton, JW; Molin, S; Eberl, L; Steinberg, P; Kjelleberg, S; Hoiby, N; Givskov, M.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Chemistry and Molecular Biosciences
 
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Created: Mon, 13 Aug 2007, 23:42:55 EST