Antimicrobial and Anti-Inflammatory Effects of Cecropin A(1-8)-Magainin2(1-12) Hybrid Peptide Analog P5 against Malassezia furfur Infection in Human Keratinocytes

The lipophilic fungus Malassezia furfur (M. furfur) is a commensal microbe associated with several chronic diseases such as pityriasis versicolor, folliculitis, and seborrheic dermatitis. Because M. furfur-related diseases are difficult to treat and require prolonged use of medications, the treatment for M. furfur-related skin diseases is supposed to gain control over M. furfur growth and the inflammation associated with it, as well as to prevent secondary infections. In this study, we investigated the antifungal and anti-inflammatory effects of cecropin A(1-8)-magainin 2(1-12) hybrid peptide analog P5 on M. furfur. The minimal inhibitory concentration of P5 against M. furfur was 0.39 mu M, making it 3-4 times more potent than commonly used antifungal agents such as ketoconazole (1.5 mu M) or itraconazole (1.14 mu M). P5 efficiently inhibited the expression of IL-8 and Toll-like receptor 2 in M. furfur-infected human keratinocytes without eukaryotic cytotoxicity at its fungicidal concentration. Moreover, P5 significantly downregulated NF-kappa B activation and intracellular calcium fluctuation, which are closely related with enhanced responses of keratinocyte inflammation induced by M. furfur infection. Taken together, these observations suggest P5 may be a potential therapeutic agent for M. furfur-associated human skin diseases because of its distinct antifungal and anti-inflammatory action.