A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation

O'Loughlin, Colleen T. and Miller, Laura C. and Siryaporn, Albert and Drescher, Knut and Semmelhack, Martin F. and Bassler, Bonnie L.. (2013) A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation. Proceedings of the National Academy of Sciences of the United States of America, 110 (44). pp. 17981-17986.

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Quorum sensing is a chemical communication process that bacteria use to regulate collective behaviors. Disabling quorum-sensing circuits with small molecules has been proposed as a potential strategy to prevent bacterial pathogenicity. The human pathogen Pseudomonas aeruginosa uses quorum sensing to control virulence and biofilm formation. Here, we analyze synthetic molecules for inhibition of the two P. aeruginosa quorum-sensing receptors, LasR and RhlR. Our most effective compound, meta-bromo-thiolactone (mBTL), inhibits both the production of the virulence factor pyocyanin and biofilm formation. mBTL also protects Caenorhabditis elegans and human lung epithelial cells from killing by P. aeruginosa. Both LasR and RhlR are partially inhibited by mBTL in vivo and in vitro; however, RhlR, not LasR, is the relevant in vivo target. More potent antagonists do not exhibit superior function in impeding virulence. Because LasR and RhlR reciprocally control crucial virulence factors, appropriately tuning rather than completely inhibiting their activities appears to hold the key to blocking pathogenesis in vivo.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Microbiology and Biophysics (Drescher)
UniBasel Contributors:Drescher, Knut
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:National Academy of Sciences
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:23 Jun 2021 08:43
Deposited On:23 Jun 2021 08:43

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