Flavuside B exhibits antioxidant and anti-inflammatory properties in Staphylococcus aureus infected skin wound and affect the expression of genes controlling bacterial quorum sensing

Abstract Aims The aim of this study was to evaluate the antioxidant and anti-inflammatory effects of marine fungal cerebroside flavuside B (FlaB) on Staphylococcus aureus-infected keratinocytes in in vitro skin wounds and to identify FlaB targets in bacterial and human cells. Methods and results A combination of ELISA, plate spectrofluorimetry, and flow cytometry with fluorescence dye staining, scratch assay, and real-time cell imaging techniques was used to investigate the effects of FlaB on S. aureus-infected HaCaT keratinocytes. FlaB decreased ROS levels, NO levels, and TNF-α and IL-18 release in S. aureus-infected HaCaT cells. FlaB reversed the inhibition of HaCaT cell proliferation caused by S. aureus infection. FlaB significantly increased keratinocyte migration and wound healing in an in vitro S. aureus-infected wound skin model. Using real-time qPCR, we found that FlaB caused a 1.7-fold reduction in agrA expression, which controls quorum sensing system in S. aureus. Bioinformatics analysis and molecular docking, together with experimental data, suggest that FlaB targets the pro/antioxidant defense system in human cells. Conclusions Thus, FlaB can play a dual role as an antibacterial and pro/antioxidant machinery modulator, providing an observable positive effect in S. aureus-infected in vitro skin wounds. Staphylococcal sortase A enzyme and Arg systems are the targets of FlaB in bacterial cells. Nrf2/Bach1 dependent pro/antioxidant defense system is a target of FlaB in human cells. Some suggestions have also been made regarding the biological role of this marine fungal metabolite and its therapeutic possibilities.