Screening of Bacterial Quorum Sensing Inhibitors in a <i>Vibrio fischeri</i> LuxR-Based Synthetic Fluorescent <i>E. coli</i> Biosensor

• Main Authors: Xiaofei Qin, Celina Vila-Sanjurjo, Ratna Singh, Bodo Philipp, Francisco M. Goycoolea
• Format: Article
• Language: English
• Published: MDPI AG 2020-09-01
• Series: Pharmaceuticals
• Subjects: compounds screening; quorum sensing inhibition; antibacterial; molecular docking
• Online Access: https://www.mdpi.com/1424-8247/13/9/263

A library of 23 pure compounds of varying structural and chemical characteristics was screened for their quorum sensing (QS) inhibition activity using a synthetic fluorescent <i>Escherichia coli</i> biosensor that incorporates a modified version of lux regulon of <i>Vibrio fischeri</i>. Four such compounds exhibited QS inhibition activity without compromising bacterial growth, namely, phenazine carboxylic acid (PCA), 2-heptyl-3-hydroxy-4-quinolone (PQS), 1<i>H</i>-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 <i>trans</i>-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 <i>Pseudomonas aeruginosa</i>, 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 virulence.