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

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Skogman , M E , Kanerva , S , Manner , S , Vuorela , P M & Fallarero , A 2016 , ' Flavones as Quorum Sensing Inhibitors Identified by a Newly Optimized Screening Platform Using Chromobacterium violaceum as Reporter Bacteria ' Molecules , vol. 21 , no. 9 , 1211 . DOI: 10.3390/molecules21091211

Title: Flavones as Quorum Sensing Inhibitors Identified by a Newly Optimized Screening Platform Using Chromobacterium violaceum as Reporter Bacteria
Author: Skogman, Malena E.; Kanerva, Sonja; Manner, Suvi; Vuorela, Pia M.; Fallarero, Adyary
Contributor: University of Helsinki, Division of Pharmaceutical Biosciences
University of Helsinki, de Vos & Salonen group
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Division of Pharmaceutical Biosciences
Date: 2016-09
Language: eng
Number of pages: 11
Belongs to series: Molecules
ISSN: 1420-3049
URI: http://hdl.handle.net/10138/168795
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 M. 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.
Subject: quorum sensing
quorum sensing inhibition
Chromobacterium violaceum
screening
flavonoids
flavones
violacein quantification
assay optimization
anti-biofilm
microcolonies
STAPHYLOCOCCUS-AUREUS BIOFILMS
PSEUDOMONAS-AERUGINOSA PAO1
ESCHERICHIA-COLI
TEA POLYPHENOLS
ANTIBACTERIAL
COMMUNICATION
RESAZURIN
HIERARCHY
LACTONES
EXTRACT
317 Pharmacy
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