Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors

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...

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Bibliographic Details
Published in:The EMBO journal 2003-08, Vol.22 (15), p.3803-3815
Main Authors: Givskov, Michael, 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, Kjelleberg, Staffan, Høiby, Niels
Format: Article
Language:English
Subjects:
Animals
antagonists
Antibiotics
Bacteria
Bacterial Proteins - biosynthesis
biofilm
Biofilms
EMBO09
EMBO23
furanone
Furans - metabolism
GeneChip
Genes, Bacterial
Immune response
Infectious diseases
Marine environment
Mice
Mice, Inbred CBA
microarray
Pseudomonas aeruginosa - genetics
Pseudomonas aeruginosa - pathogenicity
quorum sensing
Regulon
Virulence
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Summary: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 ® 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.
ISSN:0261-4189
1460-2075
1460-2075
DOI:10.1093/emboj/cdg366