Biofilm formation of Staphylococcus aureus is one of its mechanisms of drug resistance. Antibiofilm screening of 106 compounds from marine-derived fungi displayed that 12 compounds inhibited S. aureus biofilm formation by >50% at the concentration of 100 μg/ml, and only secalonic acid D (SAD) and B inhibited by >90% at 6.25 μg/ml without inhibiting cell growth after 24-h incubation. Meanwhile, it was found that the double bond between C-1 and C-10 of citrinin derivatives and the C-C connection position of two chromone monomers may be important for their anti-biofilm activities. Moreover, SAD slightly facilitated biofilm eradication and influenced its architecture. Furthermore, SAD slowed the cell growth rate in the preceding 18-h incubation and differentially regulated transcriptional expression of several genes, such as agr, isaA, icaA, and icaD, associated with biofilm formation in planktonic and biofilm cells, which may be the reason for the anti-biofilm activity of SAD. Finally, SAD acted synergistically against S. aureus growth and biofilm formation with other antibiotics. These findings indicated that various natural products from marine-derived fungi, such as SAD, could be used as a potential biofilm inhibitor against S. aureus.
Keywords: Anti-biofilm activity; Staphylococcus aureus; marine natural product; mechanism of action; secalonic acid D.