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  • The EMBO Journal (2003) 22, 3803 - 3815
  • doi:10.1093/emboj/cdg366

Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors

Morten Hentzer1, Hong Wu2, Jens Bo Andersen1, Kathrin Riedel3, Thomas B. Rasmussen1, Niels Bagge4, Naresh Kumar5, Mark A. Schembri1, Zhijun Song2, Peter Kristoffersen1, Mike Manefield6, John W. Costerton7, Søren Molin1, Leo Eberl3, Peter Steinberg8, Staffan Kjelleberg8, Niels Høiby2,4 and Michael Givskov1

  1. BioCentrum-DTU, Technical University of Denmark, DK-2800 Lyngby, Denmark
  2. Department of Clinical Microbiology, Rigshospitalet, DK-2100 Copenhagen Ø, Denmark
  3. Lehrstuhl für Mikrobiologie, Technische Universität München, D-85350 Freising, Germany
  4. Department of Bacteriology, Institute of Medical Microbiology and Immunology, University of Copenhagen, Denmark
  5. School of Chemical Sciences, University of New South Wales, NSW 2052, Australia
  6. Centre for Ecology and Hydrology Oxford, Mansfield Road, Oxford OX1 3SR, UK
  7. Center for Biofilm Engineering, Montana State University, Bozeman, MT 59717, USA
  8. Center for Marine Biofouling and Bioinnovation, University of New South Wales, NSW 2052, Australia

Correspondence to:

Michael Givskov, E-mail: immg@pop.dtu.dk

Received 11 December 2002; Accepted 2 June 2003; Revised 8 May 2003

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.

  • Keywords:

    • antagonists,
    • biofilm,
    • furanone,
    • GeneChip,
    • microarray,
    • quorum sensing