Qin, XiaofeiVila Sanjurjo, CelinaSingh, RatnaPhilipp, BodoGoycoolea, Francisco M.2020-11-102020-11-102020Qin, X.; Vila-Sanjurjo, C.; Singh, R.; Philipp, B.; Goycoolea, F.M. Screening of Bacterial Quorum Sensing Inhibitors in a Vibrio fischeri LuxR-Based Synthetic Fluorescent E. coli Biosensor. Pharmaceuticals 2020, 13, 263http://hdl.handle.net/10347/23631A library of 23 pure compounds of varying structural and chemical characteristics was screened for their quorum sensing (QS) inhibition activity using a synthetic fluorescent Escherichia coli biosensor that incorporates a modified version of lux regulon of Vibrio fischeri. Four such compounds exhibited QS inhibition activity without compromising bacterial growth, namely, phenazine carboxylic acid (PCA), 2-heptyl-3-hydroxy-4-quinolone (PQS), 1H-2-methyl-4-quinolone (MOQ) and genipin. When applied at 50 µM, these compounds reduced the QS response of the biosensor to 33.7% ± 2.6%, 43.1% ± 2.7%, 62.2% ± 6.3% and 43.3% ± 1.2%, respectively. A series of compounds only showed activity when tested at higher concentrations. This was the case of caffeine, which, when applied at 1 mM, reduced the QS to 47% ± 4.2%. In turn, capsaicin, caffeic acid phenethyl ester (CAPE), furanone and polygodial exhibited antibacterial activity when applied at 1mM, and reduced the bacterial growth by 12.8% ± 10.1%, 24.4% ± 7.0%, 91.4% ± 7.4% and 97.5% ± 3.8%, respectively. Similarly, we confirmed that trans-cinnamaldehyde and vanillin, when tested at 1 mM, reduced the QS response to 68.3% ± 4.9% and 27.1% ± 7.4%, respectively, though at the expense of concomitantly reducing cell growth by 18.6% ± 2.5% and 16% ± 2.2%, respectively. Two QS natural compounds of Pseudomonas aeruginosa, namely PQS and PCA, and the related, synthetic compounds MOQ, 1H-3-hydroxyl-4-quinolone (HOQ) and 1H-2-methyl-3-hydroxyl-4-quinolone (MHOQ) were used in molecular docking studies with the binding domain of the QS receptor TraR as a target. We offer here a general interpretation of structure-function relationships in this class of compounds that underpins their potential application as alternatives to antibiotics in controlling bacterial virulenceeng© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Compounds screeningQuorum sensing inhibitionAntibacterialMolecular dockingjournal article10.3390/ph130902631424-8247open access