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Molecules 2016, 21(9), 1211; doi:10.3390/molecules21091211

Flavones as Quorum Sensing Inhibitors Identified by a Newly Optimized Screening Platform Using Chromobacterium violaceum as Reporter Bacteria

1
Pharmaceutical Design and Discovery Group (PharmDD), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, Viikinkaari 5E, University of Helsinki, FI-00014 Helsinki, Finland
2
Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Abo Akademi University, BioCity, Artillerigatan 6 A, FI-20520 Turku, Finland
*
Author to whom correspondence should be addressed.
Academic Editor: Nancy D. Turner
Received: 4 July 2016 / Revised: 1 September 2016 / Accepted: 5 September 2016 / Published: 10 September 2016
(This article belongs to the Collection Bioactive Compounds)
View Full-Text   |   Download PDF [1682 KB, uploaded 10 September 2016]   |  

Abstract

Quorum sensing (QS) is the process by which bacteria produce and detect signal molecules to coordinate their collective behavior. This intercellular communication is a relevant target for anti-biofilm therapies. Here we have optimized a screening-applicable assay to search for new quorum sensing inhibitors from natural compound libraries. In this system, QS is correlated with the production of violacein, which is directly controlled by the LuxI/LuxR system in Chromobacterium violaceum ATCC 31532. The parallel use of C. violaceum Tn5-mutant CV026, which depends on auto-inducer addition, allows simultaneous discrimination of compounds that act as quenchers of the AHL signal (quorum quenchers). The incorporation of a redox stain into the platform allowed further distinction between QS inhibitors, quorum quenchers and antibacterial compounds. A pilot screening was performed with 465 natural and synthetic flavonoids. All the most active compounds were flavones and they displayed potencies (IC50) in the range of 3.69 to 23.35 μM. These leads were particularly promising as they inhibited the transition from microcolonies into mature biofilms from Escherichia coli and Pseudomonas aeruginosa strains. This approach can be very effective in identifying new antimicrobials posing lesser risks of resistance. View Full-Text
Keywords: quorum sensing; quorum sensing inhibition; Chromobacterium violaceum; screening; flavonoids; flavones; violacein quantification; assay optimization; anti-biofilm; microcolonies quorum sensing; quorum sensing inhibition; Chromobacterium violaceum; screening; flavonoids; flavones; violacein quantification; assay optimization; anti-biofilm; microcolonies
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Skogman, M.E.; Kanerva, S.; Manner, S.; Vuorela, P.M.; Fallarero, A. Flavones as Quorum Sensing Inhibitors Identified by a Newly Optimized Screening Platform Using Chromobacterium violaceum as Reporter Bacteria. Molecules 2016, 21, 1211.

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