Engineering Research Center of Industrial Biocatalysis, Fujian Province University, Fujian Provincial Key Laboratory of Advanced Materials Oriented Chemical Engineering, Fujian Provincial Key Laboratory of Polymer Materials, Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, College of Chemistry and Materials Science, Fujian Normal University, 32 Shangsan Road, Fuzhou 350007, People's Republic of China.
Department of Natural Medicine and Pharmacognosy, School of Pharmacy, Qingdao University, 308 Ningxia Road, Qingdao 266071, People's Republic of China.
Bioorg Chem. 2021 Jun;111:104894. doi: 10.1016/j.bioorg.2021.104894. Epub 2021 Apr 8.
We recently and for the first time reported that ethyl acetate extracts isolated from Penicillium chrysogenum DXY-1 exhibited anti-quorum sensing (anti-QS) activity. Herein, another active molecule in the extracts was identified as chrysin by NMR and MS. A 20 μg/mL dose of chrysin inhibited violacein production regulated by QS in C. violaceum CV026 by 31.6%. A 40 μg/mL dose of chrysin suppressed pyocyanin production, elastase activity, proteolytic activity, and biofilm formation regulated by QS in P. aeruginosa PA01 by 41.4%, 13.8%, 8.3%, and 42.4%, respectively. And chrysin could inhibit the swarming activity of P. aeruginosa PA01. Further, molecular docking and CD analysis were used to address the mechanism of chrysin's activity in C. violaceum. Molecular docking results revealed that chrysin suppresses QS system by competing with the natural signal molecule CHSL for binding to the same pocket of CviR receptor. At the same time, CD results also showed that chrysin could change the secondary structure composition of CviR, which greatly prevented the binding of CHSL/CviR, and further playing its role on inhibiting bacterial QS system. All these data demonstate that chrysin may be used as a potential QS inhibitor to tackle increasing drug resistance.
我们最近首次报道，从青霉（Penicillium chrysogenum）DXY-1 中分离出的乙酸乙酯提取物具有抗群体感应（anti-QS）活性。在此，通过 NMR 和 MS 鉴定出提取物中的另一种活性分子为白杨素。白杨素的浓度为 20μg/mL 时，对 CV026 中由 QS 调控的紫色素产生的抑制率为 31.6%。白杨素的浓度为 40μg/mL 时，对 PA01 中由 QS 调控的绿脓菌素产生、弹性蛋白酶活性、蛋白水解活性和生物膜形成的抑制率分别为 41.4%、13.8%、8.3%和 42.4%。此外，白杨素可抑制铜绿假单胞菌 PA01 的群集活性。进一步的分子对接和 CD 分析用于阐明白杨素在 CV026 中的作用机制。分子对接结果表明，白杨素通过与天然信号分子 CHSL 竞争结合 CviR 受体的相同口袋来抑制 QS 系统。同时，CD 结果也表明，白杨素可以改变 CviR 的二级结构组成，从而大大阻止了 CHSL/CviR 的结合，进一步发挥其抑制细菌 QS 系统的作用。所有这些数据表明，白杨素可能被用作一种潜在的 QS 抑制剂，以应对日益增加的药物耐药性。
