Validation of PqsD as an Anti-biofilm Target in Pseudomonas aeruginosa by Development of Small-Molecule Inhibitors
Journal of the American Chemical Society2012Vol. 134(39), pp. 16143–16146
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Michael P. Storz, Christine K. Maurer, Christina Zimmer, Nathalie Wagner, Christian Brengel, Johannes C. de Jong, Simon Lucas, Mathias Müsken, Susanne Häußler, Anke Steinbach, Rolf W. Hartmann
Abstract
2-Heptyl-4-hydroxyquinoline (HHQ) and Pseudomonas quinolone signal (PQS) are involved in the regulation of virulence factor production and biofilm formation in Pseudomonas aeruginosa. PqsD is a key enzyme in the biosynthesis of these signal molecules. Using a ligand-based approach, we have identified the first class of PqsD inhibitors. Simplification and rigidization led to fragments with high ligand efficiencies. These small molecules repress HHQ and PQS production and biofilm formation in P. aeruginosa. This validates PqsD as a target for the development of anti-infectives.
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