Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors
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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; Steinberg, Peter; Kjelleberg, Staffan; Høiby, Niels; Givskov, Michael.
In: EMBO Journal, Vol. 22, No. 15, 2003, p. 3803-15.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors
AU - Hentzer, Morten
AU - Wu, Hong
AU - Andersen, Jens Bo
AU - Riedel, Kathrin
AU - Rasmussen, Thomas B
AU - Bagge, Niels
AU - Kumar, Naresh
AU - Schembri, Mark A
AU - Song, Zhijun
AU - Kristoffersen, Peter
AU - Manefield, Mike
AU - Costerton, John W
AU - Molin, Søren
AU - Eberl, Leo
AU - Steinberg, Peter
AU - Kjelleberg, Staffan
AU - Høiby, Niels
AU - Givskov, Michael
N1 - Keywords: Animals; Bacterial Proteins; Furans; Genes, Bacterial; Mice; Mice, Inbred CBA; Pseudomonas aeruginosa; Regulon; Virulence
PY - 2003
Y1 - 2003
N2 - 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.
AB - 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.
U2 - 10.1093/emboj/cdg366
DO - 10.1093/emboj/cdg366
M3 - Journal article
C2 - 12881415
VL - 22
SP - 3803
EP - 3815
JO - E M B O Journal
JF - E M B O Journal
SN - 0261-4189
IS - 15
ER -
ID: 10615282