Fujian Provincial University Engineering Research Center of Industrial Biocatalysis, Fujian Provincial Key Laboratory of Advanced Materials Oriented Chemical Engineering, 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. 2019 Oct;91:103140. doi: 10.1016/j.bioorg.2019.103140. Epub 2019 Jul 22.
An ethyl acetate extracts isolated from a marine fungal strain, Penicillium chrysogenum DXY-1, obtained from marine sediments surrounding the East Sea, was found to exhibit anti-quorum sensing (anti-QS) activity. Interestingly, a novel active compound was identified as tyrosol by the purification and structural characterization. At a concentration of 0.5 mg/mL, tyrosol decreased QS-regulated violacein production in Chromobacterium violaceum CV026 by 53.5% and decreased QS-regulated pyocyanin production, elastase activity and proteolytic activity in Pseudomonas aeruginosa PA01 by 63.3%, 57.8% and 9.9%, respectively. SEM images showed that tyrosol inhibited biofilm formation in P. aeruginosa PA01 without having any effect on bacterial growth. Molecular docking results revealed that the natural signal molecule CHSL and tyrosol bound to different receptor pockets of CviR, and tyrosol inhibited the QS activity of CviR in C. violaceum by binding to the DNA-binding domain and blocking pathogenic gene expression. All the data suggest that tyrosol may act as a potential inhibitor of the QS systems to solve the looming crisis of bacterial resistance. We believe that there are other active compounds with relatively high anti-QS activity or synergistic inhibitory effects on QS in the crude extract, which warrants further research.
从东海周边海洋沉积物中分离得到的海洋真菌菌株青霉 DXY-1 的乙酸乙酯提取物表现出抗群体感应（anti-QS）活性。有趣的是，通过纯化和结构表征，鉴定出一种新型活性化合物为酪醇。在 0.5mg/mL 浓度下，酪醇使紫色杆菌 CV026 的 QS 调控的紫色素产量降低了 53.5%，使铜绿假单胞菌 PA01 的 QS 调控的绿脓菌素产量、弹性蛋白酶活性和蛋白水解活性分别降低了 63.3%、57.8%和 9.9%。SEM 图像显示，酪醇抑制了铜绿假单胞菌 PA01 的生物膜形成，而对细菌生长没有任何影响。分子对接结果表明，天然信号分子 CHSL 和酪醇结合到 CviR 的不同受体口袋中，并且酪醇通过结合 DNA 结合域并阻断致病基因表达来抑制 C. violaceum 中的 CviR 的 QS 活性。所有数据表明，酪醇可能作为一种潜在的 QS 系统抑制剂来解决细菌耐药性日益严重的危机。我们相信，粗提物中可能存在其他具有相对较高抗 QS 活性或对 QS 具有协同抑制作用的活性化合物，值得进一步研究。
