| Summary: | <i>Pseudomonas aeruginosa</i> is an opportunistic pathogen that infects patients by regulating virulence factors and biofilms through a quorum sensing (QS) system to protect itself from antibiotics and environmental stress. Therefore, the development of quorum sensing inhibitors (QSIs) is expected to become a new strategy for studying drug resistance to <i>P. aeruginosa</i> infections. Marine fungi are valuable resources for screening QSIs. A marine fungus, <i>Penicillium</i> sp. JH1, with anti-QS activity was isolated from the offshore waters of Qingdao (China), and citrinin, a novel QSI, was purified from secondary metabolites of this fungus. Citrinin could significantly inhibit the production of violacein in <i>Chromobacterium violaceum</i> CV12472 and the production of three virulence factors (elastase, rhamnolipid and pyocyanin) in <i>P. aeruginosa</i> PAO1. It could also inhibit the biofilm formation and motility of PAO1. In addition, citrinin downregulated the transcript levels of nine genes (<i>lasI</i>, <i>rhlI</i>, <i>pqsA</i>, <i>lasR</i>, <i>rhlR</i>, <i>pqsR</i>, <i>lasB</i>, <i>rhlA</i> and <i>phzH</i>) associated with QS. Molecular docking results showed that citrinin bound to PqsR and LasR with better affinity than the natural ligands. This study laid a foundation for the further study of the structure optimization and structure–activity relationship of citrinin.
|
|---|