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

TitleA quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation.
Publication TypeJournal Article
Year of Publication2013
AuthorsO'Loughlin, CT, Miller, LC, Siryaporn, A, Drescher, K, Semmelhack, MF, Bassler, BL
JournalProc Natl Acad Sci U S A
Volume110
Issue44
Pagination17981-6
Date Published2013 Oct 29
ISSN1091-6490
KeywordsAnimals, 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>

DOI10.1073/pnas.1316981110
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID24143808
PubMed Central IDPMC3816427
Grant List5R01GM065859 / GM / NIGMS NIH HHS / United States
F32 AI095002 / AI / NIAID NIH HHS / United States
F32AI095002 / AI / NIAID NIH HHS / United States
P50 GM071508 / GM / NIGMS NIH HHS / United States
R01 GM065859 / GM / NIGMS NIH HHS / United States
/ / Howard Hughes Medical Institute / United States