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Abstract：
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 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 virulence.
摘要：
使用合成的荧光大肠杆菌生物传感器筛选了具有不同结构和化学特性的23种纯化合物文库的群体感应（QS）抑制活性，该传感器结合了费氏弧菌的lux调节子的改良版本。四个这样的化合物表现出QS抑制活性而不损害细菌生长，即,吩嗪羧酸（PCA），2-庚基-3-羟基-4-喹诺酮(PQS),1H-2-甲基-4-喹诺酮(MOQ)和京尼平。当在50µM下使用时，这些化合物将生物传感器的QS响应降低到33.7%±2.6%，43.1%±2.7%,62.2%±6.3%和43.3%±1.2%，分别。一系列化合物仅在较高浓度下测试时显示活性。咖啡因就是这样，which,当应用于1mM时，将QS降至47%±4.2%。反过来,辣椒素,咖啡酸苯乙酯（CAPE），呋喃酮和多角菌在1mM时表现出抗菌活性，细菌生长减少12.8%±10.1%，24.4%±7.0%,91.4%±7.4%和97.5%±3.8%，分别。同样，我们确认了反式肉桂醛和香兰素,当在1mM下测试时，将QS反应降低至68.3%±4.9%和27.1%±7.4%，分别,尽管以同时减少18.6%±2.5%和16%±2.2%的细胞生长为代价，分别。铜绿假单胞菌的两种QS天然化合物,即PQS和PCA，和相关的，合成化合物MOQ，1H-3-羟基-4-喹诺酮（HOQ）和1H-2-甲基-3-羟基-4-喹诺酮（MHOQ）用于分子对接研究，以QS受体TraR的结合域为靶标。我们在这里提供了这类化合物中结构-功能关系的一般解释，这些化合物是它们在控制细菌毒力方面作为抗生素替代品的潜在应用的基础。
