| Summary: | <i>Pseudomonas aeruginosa</i> 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 <i>P. aeruginosa</i> infections without killing the bacteria, meaning that it is much harder for bacteria to develop drug resistance. A marine fungus <i>Cladosporium</i> 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 (<i>lasR, rhlR and pqsR</i>), autoinducer synthases (<i>lasI, rhlI and pqsA</i>) and virulence factors (<i>lasB and rhlA</i>) 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 <i>P. aeruginosa</i>, and its structure–activity relationships should be further studied to illustrate the mode of action, optimize its structure and improve anti-QS activity.
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