Fernandes Susana, Borges Anabela, Gomes Inês B, Sousa Sérgio F, Simões Manuel
LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal; ALiCE - Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal.
UCIBIO/REQUIMTE, BioSIM, Departamento de Biomedicina, Faculdade de Medicina da Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.
Food Res Int. 2023 Mar;165:112519. doi: 10.1016/j.foodres.2023.112519. Epub 2023 Jan 24.
The quorum sensing (QS) system is related to cell-to-cell communication as a function of population density, which regulates several physiological functions including biofilm formation and virulence gene expression. QS inhibitors have emerged as a promising strategy to tackle virulence and biofilm development. Among a wide variety of phytochemicals, many of them have been described as QS inhibitors. Driven by their promising clues, this study aimed to identify active phytochemicals against LuxS/autoinducer-2 (AI-2) (as the universal QS system) from Bacillus subtilis and LasI/LasR (as a specific QS system) of Pseudomonas aeruginosa, through in silico analysis followed by in vitro validation. The optimized virtual screening protocols were applied to screen a phytochemical database containing 3479 drug-like compounds. The most promising phytochemicals were curcumin, pioglitazone hydrochloride, and 10-undecenoic acid. In vitro analysis corroborated the QS inhibitory activity of curcumin and 10-undecenoic acid, however, pioglitazone hydrochloride showed no relevant effect. Inhibitory effects on LuxS/AI-2 QS system triggered reduction of 33-77% by curcumin (at 1.25-5 µg/mL) and 36-64% by 10-undecenoic acid (at 12.5-50 µg/mL). Inhibition of LasI/LasR QS system was 21% by curcumin (at 200 µg/mL) and 10-54% by 10-undecenoic acid (at 15.625-250 µg/mL). In conclusion, in silico analysis allowed the identification of curcumin and, for the first time, 10-undecenoic acid (showing low cost, high availability, and low toxicity) as alternatives to counteract bacterial pathogenicity and virulence, avoiding the imposition of selective pressure usually related to classic industrial disinfection and antibiotics therapy.
群体感应（QS）系统与细胞间通讯有关，它是群体密度的一种功能，可调节包括生物膜形成和毒力基因表达在内的多种生理功能。群体感应抑制剂已成为应对毒力和生物膜形成的一种有前景的策略。在各种各样的植物化学物质中，许多已被描述为群体感应抑制剂。受这些有前景线索的驱动，本研究旨在通过计算机分析随后进行体外验证，从枯草芽孢杆菌的LuxS/自诱导物-2（AI-2）（作为通用群体感应系统）和铜绿假单胞菌的LasI/LasR（作为特定群体感应系统）中鉴定出具有活性的植物化学物质。应用优化的虚拟筛选方案筛选了一个包含3479种类药物化合物的植物化学物质数据库。最有前景的植物化学物质是姜黄素、盐酸吡格列酮和10-十一碳烯酸。体外分析证实了姜黄素和10-十一碳烯酸的群体感应抑制活性，然而，盐酸吡格列酮未显示出相关作用。对LuxS/AI-2群体感应系统的抑制作用，姜黄素（在1.25 - 5μg/mL时）引发了33 - 77%的降低，10-十一碳烯酸（在12.5 - 50μg/mL时）引发了36 - 64%的降低。对LasI/LasR群体感应系统的抑制作用，姜黄素（在200μg/mL时）为21%，10-十一碳烯酸（在15.625 - 250μg/mL时）为10 - 54%。总之，计算机分析首次鉴定出姜黄素和10-十一碳烯酸（显示出低成本、高可用性和低毒性）可作为对抗细菌致病性和毒力的替代物，避免了通常与传统工业消毒和抗生素治疗相关的选择性压力。
