School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, 1 Wenhai Road, Qingdao 266237, China.
Mar Drugs. 2020 Apr 10;18(4):205. doi: 10.3390/md18040205.
is an opportunistic pathogen using virulence factors and biofilm regulated by quorum sensing (QS) systems to infect patients and protect itself from environmental stress and antibiotics. Interfering with QS systems is a novel approach to combat infections without killing the bacteria, meaning that it is much harder for bacteria to develop drug resistance. A marine fungus sp. Z148 with anti-QS activity was obtained from Jiaozhou Bay, China. Cladodionen, a novel QS inhibitor, was isolated from the extracts of this fungus. Cladodionen had a better inhibitory effect than pyocyanin on the production of elastase and rhamnolipid. It also inhibited biofilm formation and motilities. The mRNA expressions of QS-related genes, including receptor proteins (), autoinducer synthases () and virulence factors () were down-regulated by cladodionen. Molecular docking analysis showed that cladodionen had better binding affinity to LasR and PqsR than natural ligands. Moreover, the binding affinity of cladodionen to LasR was higher than to PqsR. Cladodionen exhibits potential as a QS inhibitor against , and its structure-activity relationships should be further studied to illustrate the mode of action, optimize its structure and improve anti-QS activity.
是一种机会性病原体，利用毒力因子和群体感应（QS）系统调节的生物膜来感染患者，并保护自身免受环境压力和抗生素的影响。干扰 QS 系统是一种对抗 感染的新方法，而不会杀死细菌，这意味着细菌更难产生耐药性。一种具有抗 QS 活性的海洋真菌 sp. Z148 从中国胶州湾获得。从该真菌的提取物中分离到一种新型的 QS 抑制剂，命名为 cladodionen。与绿脓菌素相比，cladodionen 对弹性蛋白酶和鼠李糖脂的产生具有更好的抑制作用。它还抑制生物膜形成和运动性。QS 相关基因（包括受体蛋白 ()、自诱导物合成酶 () 和毒力因子 ()）的 mRNA 表达被 cladodionen 下调。分子对接分析表明，cladodionen 与 LasR 和 PqsR 的结合亲和力优于天然配体。此外，cladodionen 与 LasR 的结合亲和力高于与 PqsR 的结合亲和力。cladodionen 作为一种针对 的 QS 抑制剂具有潜力，应进一步研究其结构-活性关系，以阐明其作用模式、优化其结构并提高其抗 QS 活性。
