Title | A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | O'Loughlin, CT, Miller, LC, Siryaporn, A, Drescher, K, Semmelhack, MF, Bassler, BL |
Journal | Proc Natl Acad Sci U S A |
Volume | 110 |
Issue | 44 |
Pagination | 17981-6 |
Date Published | 2013 Oct 29 |
ISSN | 1091-6490 |
Keywords | Animals, Bacterial Proteins, Biofilms, Caenorhabditis elegans, Cell Line, Escherichia coli, Humans, Lactones, Microarray Analysis, Molecular Structure, Pseudomonas aeruginosa, Pyocyanine, Quorum Sensing, Respiratory Mucosa, Sulfur Compounds, Trans-Activators, Virulence |
Abstract | <p>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.</p> |
DOI | 10.1073/pnas.1316981110 |
Alternate Journal | Proc Natl Acad Sci U S A |
PubMed ID | 24143808 |
PubMed Central ID | PMC3816427 |
Grant List | / HHMI / Howard Hughes Medical Institute / United States P50 GM071508 / GM / NIGMS NIH HHS / United States F32AI095002 / AI / NIAID NIH HHS / United States 5R01GM065859 / GM / NIGMS NIH HHS / United States F32 AI095002 / AI / NIAID NIH HHS / United States R01 GM065859 / GM / NIGMS NIH HHS / United States |