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

作者: H Wu , Z Song , Morten Hentzer , Jens Bo Andersen , Søren Molin

DOI: 10.1093/JAC/DKH223

关键词: BiofilmQuorum sensingBacteriaAntibioticsPseudomonadaceaeHomoserineEscherichia coliMicrobiologyPseudomonas aeruginosaBiology

摘要: Introduction: Antibiotics are used to treat bacterial infections by killing the bacteria or inhibiting their growth, but resistance antibiotics can develop readily. The discovery that quorum-sensing regulates virulence as well formation of biofilms opens up new ways control certain infections. Furanone compounds capable systems have been isolated from marine macro alga Delisea pulchra. Objectives: Two synthetic furanones were tested for ability attenuate in mouse models chronic lung infection targeting without directly growth. Methods: Study I. Mice with Escherichia coli MT102 [luxR-Pluxl-gfp(ASV)] injected intravenously N-acyl homoserine lactones test interference quorum-sensing. II. Pseudomonas aeruginosa PAO1 [dsred, lasR-PlasB-gfp(ASV)] evaluate effects on III. P. treated different doses therapeutic infection. Results: Furanones successfully interfered lactone and suppressed lungs, which resulted decreases expression green fluorescent protein. accelerated clearance, reduced severity pathology. In a lethal infection, treatment furanone significantly prolonged survival time mice. Conclusion: Synthetic inhibited exhibited favourable

参考文章(28)
Pradeep K. Singh, Amy L. Schaefer, Matthew R. Parsek, Thomas O. Moninger, Michael J. Welsh, E. P. Greenberg, Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms Nature. ,vol. 407, pp. 762- 764 ,(2000) , 10.1038/35037627
Gary Telford, D. Wheeler, Paul Williams, P. T. Tomkins, P. Appleby, Herbert Sewell, Gordon S. A. B. Stewart, Barrie W. Bycroft, David I. Pritchard, The Pseudomonas aeruginosa Quorum-Sensing Signal Molecule N-(3-Oxododecanoyl)-l-Homoserine Lactone Has Immunomodulatory Activity Infection and Immunity. ,vol. 66, pp. 36- 42 ,(1998) , 10.1128/IAI.66.1.36-42.1998
Michael Manefield, Thomas Bovbjerg Rasmussen, Morten Henzter, Jens Bo Andersen, Peter Steinberg, Staffan Kjelleberg, Michael Givskov, Halogenated furanones inhibit quorum sensing through accelerated LuxR turnover. Microbiology. ,vol. 148, pp. 1119- 1127 ,(2002) , 10.1099/00221287-148-4-1119
James P. Pearson, Matthew Feldman, Barbara H. Iglewski, Alice Prince, Pseudomonas aeruginosa Cell-to-Cell Signaling Is Required for Virulence in a Model of Acute Pulmonary Infection Infection and Immunity. ,vol. 68, pp. 4331- 4334 ,(2000) , 10.1128/IAI.68.7.4331-4334.2000
Michael Manefield, Rocky de Nys, Kumar Naresh, Read Roger, Michael Givskov, Steinberg Peter, Staffan Kjelleberg, Evidence that halogenated furanones from Delisea pulchra inhibit acylated homoserine lactone (AHL)-mediated gene expression by displacing the AHL signal from its receptor protein. Microbiology. ,vol. 145, pp. 283- 291 ,(1999) , 10.1099/13500872-145-2-283
Giles Hartman, Richard Wise, Quorum sensing: potential means of treating gram-negative infections? The Lancet. ,vol. 351, pp. 848- 849 ,(1998) , 10.1016/S0140-6736(05)70282-8
SVEND STENVANG Pedersen, GEOFFREY H. Shand, BENTE LANGVAD Hansen, GEORG NØRGAARD Hansen, Induction of experimental chronic Pseudomonas aeruginosa lung infection with P. aeruginosa entrapped in alginate microspheres. Apmis. ,vol. 98, pp. 203- 211 ,(1990) , 10.1111/J.1699-0463.1990.TB01023.X
CLAUS MOSER, HELLE KROGH JOHANSEN, ZHIJUN SONG, HANS PETTER HOUGEN, JØRGEN RYGAARD, NIELS HØIBY, Chronic Pseudomonas aeruginosa lung infection is more severe in Th2 responding BALB/c mice compared to Th1 responding C3H/HeN mice Apmis. ,vol. 105, pp. 838- 842 ,(1997) , 10.1111/J.1699-0463.1997.TB05092.X