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J Antimicrob Chemother. 2004 Jun;53(6):1054-61. Epub 2004 Apr 29.

Synthetic furanones inhibit quorum-sensing and enhance bacterial clearance in Pseudomonas aeruginosa lung infection in mice.

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1
Department of Clinical Microbiology, University Hospital of Copenhagen (Rigshospitalet), Juliane Marie Vej 22, Copenhagen Ø, DK-2100. wuhong@get2net.dk

Abstract

INTRODUCTION:

Antibiotics are used to treat bacterial infections by killing the bacteria or inhibiting their growth, but resistance to antibiotics can develop readily. The discovery that bacterial quorum-sensing regulates bacterial virulence as well as the formation of biofilms opens up new ways to control certain bacterial infections. Furanone compounds capable of inhibiting bacterial quorum-sensing systems have been isolated from the marine macro alga Delisea pulchra.

OBJECTIVES:

Two synthetic furanones were tested for their ability to attenuate bacterial virulence in the mouse models of chronic lung infection by targeting bacterial quorum-sensing without directly killing bacteria or inhibiting their growth.

METHODS:

Study I. Mice with Escherichia coli MT102 [luxR-PluxI-gfp(ASV)] lung infection were injected intravenously with N-acyl homoserine lactones with or without furanones to test the interference of furanones with quorum-sensing. Study II. Mice with lung infection by Pseudomonas aeruginosa PAO1 [dsred, lasR-PlasB-gfp(ASV)] were injected intravenously with furanones to evaluate their inhibiting effects on quorum-sensing. Study III. Mice with P. aeruginosa PAO1 lung infection were treated with different doses of furanones to evaluate the therapeutic effects of furanones on the lung infection.

RESULTS:

Furanones successfully interfered with N-acyl homoserine lactone and suppressed bacterial quorum-sensing in lungs, which resulted in decreases in expression of green fluorescent protein. Furanones accelerated lung bacterial clearance, and reduced the severity of lung pathology. In a lethal P. aeruginosa lung infection, treatment with furanone significantly prolonged the survival time of the mice.

CONCLUSION:

Synthetic furanone compounds inhibited bacterial quorum-sensing in P. aeruginosa and exhibited favourable therapeutic effects on P. aeruginosa lung infection.

PMID:
15117922
DOI:
10.1093/jac/dkh223
[Indexed for MEDLINE]
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