Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors

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

SN - 0261-4189

VL - 22

SP - 3803

EP - 3815

JO - EMBO Journal

JF - EMBO Journal

IS - 15

ER -