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Int. J. Mol. Sci. 2018, 19(5), 1346; https://doi.org/10.3390/ijms19051346

Screening of Natural Product Derivatives Identifies Two Structurally Related Flavonoids as Potent Quorum Sensing Inhibitors against Gram-Negative Bacteria

1
Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Artillerigatan 6A, FI-20520 Turku, Finland
2
Pharmaceutical Design and Discovery (PharmDD), Pharmaceutical Biology, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5E, P.O. Box 56, FI-00014 Helsinki, Finland
*
Author to whom correspondence should be addressed.
Received: 1 April 2018 / Revised: 28 April 2018 / Accepted: 30 April 2018 / Published: 3 May 2018
(This article belongs to the Section Bioactives and Nutraceuticals)
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Abstract

Owing to the failure of conventional antibiotics in biofilm control, alternative approaches are urgently needed. Inhibition of quorum sensing (QS) represents an attractive target since it is involved in several processes essential for biofilm formation. In this study, a compound library of natural product derivatives (n = 3040) was screened for anti-quorum sensing activity using Chromobacterium violaceum as reporter bacteria. Screening assays, based on QS-mediated violacein production and viability, were performed in parallel to identify non-bactericidal QS inhibitors (QSIs). Nine highly active QSIs were identified, while 328 compounds were classified as moderately actives and 2062 compounds as inactives. Re-testing of the highly actives at a lower concentration against C. violaceum, complemented by a literature search, led to the identification of two flavonoid derivatives as the most potent QSIs, and their impact on biofilm maturation in Escherichia coli and Pseudomonas aeruginosa was further investigated. Finally, effects of these leads on swimming and swarming motility of P. aeruginosa were quantified. The identified flavonoids affected all the studied QS-related functions at micromolar concentrations. These compounds can serve as starting points for further optimization and development of more potent QSIs as adjunctive agents used with antibiotics in the treatment of biofilms. View Full-Text
Keywords: quorum sensing; quorum sensing inhibitor; Chromobacterium violaceum; natural product derivatives; flavonoids; Pseudomonas aeruginosa; Escherichia coli quorum sensing; quorum sensing inhibitor; Chromobacterium violaceum; natural product derivatives; flavonoids; Pseudomonas aeruginosa; Escherichia coli
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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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Manner, S.; Fallarero, A. Screening of Natural Product Derivatives Identifies Two Structurally Related Flavonoids as Potent Quorum Sensing Inhibitors against Gram-Negative Bacteria. Int. J. Mol. Sci. 2018, 19, 1346.

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