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PMID: 12881415 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors.

The EMBO journal ·Vol. 22 ·No. 15 ·2003-08-01 ·Pages 3803-15

Hentzer M, Wu H, Andersen JB, Riedel K, Rasmussen TB, Bagge N, Kumar N, Schembri MA, Song Z, Kristoffersen P, Manefield M, Costerton JW, Molin S, Eberl L, Steinberg P, Kjelleberg S, Høiby N, Givskov M

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 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.

MeSH Terms
Animals Bacterial Proteins/biosynthesis Furans/metabolism Genes, Bacterial Mice Mice, Inbred CBA Pseudomonas aeruginosa/genetics,pathogenicity Regulon Virulence
Chemicals
Bacterial Proteins Furans
Authors & Affiliations
18 authors, click to expand affiliations / ORCID
Hentzer Morten
BioCentrum-DTU, Technical University of Denmark, DK-2800 Lyngby, Denmark.
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
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdg366
Published
2003-08-01
Pages
3803-15
Language
English
Region
England
NLM ID
8208664
PMCID
PMC169039
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/cdg366 PMC Full Text View journal details
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