JAC Advance Access published online on April 29, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh223
© 2004 by The British Society for Antimicrobial Chemotherapy
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1 Department of Clinical
Microbiology, University Hospital of Copenhagen (Rigshospitalet),
Juliane Marie Vej 22, Copenhagen
* To whom correspondence should be addressed. E-mail: wuhong{at}get2net.dk.
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.
Revised February 29, 2004
Accepted March 4, 2004
Original article
Synthetic furanones inhibit quorum-sensing and
enhance bacterial clearance in Pseudomonas aeruginosa lung
infection in mice
, DK-2100;
2 Molecular Microbiology, Building
301, BioCentrum,
The Technical University of Denmark, Lyngby, DK-2800, Denmark
Abstract 
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