An Investigation of Quorum Sensing Inhibitors against Bacillus cereus in The Endophytic Fungus Pithomyces sacchari of the Laurencia sp.

Bacillus cereus , a common food-borne pathogen, forms biofilms and generates virulence factors through a quorum sensing (QS) mechanism. In this study, six compounds (dankasterone A, demethylincisterol A 3 , zinnimidine, cyclo-(L-Val-L-Pro), cyclo-(L-Ile-L-Pro), and cyclo-(L-Leu-L-Pro)) were isolated from the endophytic fungus Pithomyces sacchari of the Laurencia sp. in the South China Sea. Among them, demethylincisterol A 3 , a sterol derivative, exhibited strong QS inhibitory activity against B. cereus . The QS inhibitory activity of demethylincisterol A 3 was evaluated through experiments. The minimum inhibitory concentration (MIC) of demethylincisterol A 3 against B. cereus was 6.25 μg/mL. At sub-MIC concentrations, it significantly decreased biofilm formation, hindered mobility, and diminished the production of protease and hemolysin activity. Moreover, RT-qPCR results demonstrated that demethylincisterol A 3 markedly inhibited the expression of QS-related genes ( plcR and papR ) in B. cereus . The exposure to demethylincisterol A3 resulted in the downregulation of genes ( comER , tasA , rpoN , sinR , codY , nheA , hblD , and cytK ) associated with biofilm formation, mobility, and virulence factors. Hence, demethylincisterol A 3 is a potentially effective compound in the pipeline of innovative antimicrobial therapies.