The Inhibitory Activity of Citral against Malassezia furfur

The lipophilic yeast Malassezia furfur, is a member of the cutaneous commensal microbiota and is associated with several chronic diseases such as dandruff, pityriasis versicolor, folliculitis, and seborrheic dermatitis, that are often difficult to treat with current therapies. The development of alternatively effective antifungal therapies is therefore of paramount importance. In this study, we investigated the treatment effect of citral on M. furfur. The minimal inhibitory concentration of citral for M. furfur was 200 mu g/mL, and the minimal fungicidal concentration was 300 mu g/mL. Citral significantly increased the proportion of yeast cells to mycelial forms 2.6-fold. Phosphatidylserine externalization, DNA fragmentation, and metacaspase activation supported a citral-induced apoptosis in M. furfur. Moreover, citral at sub-minimum inhibitory concentrations reduced the invasion of M. furfur in HaCaT keratinocytes. Finally, we demonstrated that citral inhibited IL-6 and TLR-2 expression and enhanced HBD-2 and TSLP expression in M. furfur-infected HaCaT keratinocytes. These results showed that citral has antifungal activity at high concentrations and can decrease the infection of M. furfur by modulating the keratinocyte immune responses at low concentrations. Our results suggest that citral is a potential candidate for topical therapeutic application for M. furfur-associated human skin diseases.