Malassezin, a Novel Agonist of the Aryl Hydrocarbon Receptor from the Yeast Malassezia furfur, Induces Apoptosis in Primary Human Melanocytes

Abstract

Pityriasis versicolor is the most common skin mycosis in humans worldwide. Yeasts of the genus Malassezia, particularly M. furfur, a saprophyte occurring widely on human skin, are generally regarded as the causative agents. Pityriasis versicolor is often accompanied by a long-lasting depigmentation that persists even after successful antimycotic therapy. M. furfur is able to convert tryptophan into a variety of indole alkaloids, some of them showing biological properties that correlate well with certain clinical features of pityriasis versicolor. This suggests a possible role for these compounds in the depigmentation process. We now report that human melanocytes undergo apoptosis when exposed to the crude mixture of tryptophan metabolites from M. furfur. The active compound was identified as malassezin, previously isolated by us from the same source and characterized as an agonist of the aryl hydrocarbon (Ah) receptor. The compound could, therefore, contribute to the marked depigmentation observed during the course of pityriasis versicolor.

The Malassezia Genus in Skin and Systemic Diseases

“…More specifically, a dose-dependent induction of apoptotic markers after the cultivation of melanocytes with malassezin for 24 h was reported. It was also observed that the biosynthesis of melanin is also reduced in a similar dose-dependent way (184). However, the reduction in the level of melanin is most probably due to the apoptosis of melanocytes, and it is not the result of a specific activity on the biosynthetic pathway of melanin.…”

“…However, conventional culture and identification methods offer the advantage of further evaluating the isolates for possible virulence factors, such as the production of phospholipase (44,170) and indole (108,184,336) and melanin synthesis (107). Furthermore, this was highlighted in a study by Akaza et al (6), in which the seasonal rates of isolation of Malassezia species from healthy skin determined by quantitative PCR (qPCR) were compared with those determined by use of Leeming-Notman agar (197).…”

“…Malassezin was initially isolated from ethyl acetate extracts of M. furfur cultures (336). It was found that malassezin induces the apoptosis of melanocytes (184). More specifically, a dose-dependent induction of apoptotic markers after the cultivation of melanocytes with malassezin for 24 h was reported.…”

“…Nevertheless, the characteristic hypopigmentation associated with pityriasis versicolor has been attributed to this biological action of malassezin. Hypopigmentation seems to be enhanced by the inhibition of melanin transportation from melanocytes to keratinocytes due to the breakdown of the actin cytoskeleton (184).…”

Modifying skin pigmentation – approaches through intrinsic biochemistry and exogenous agents

“…Tryptophan metabolites from malassezia yeast induce apoptosis in human melanocytes, which leads to depigmentation of the skin (pityriasis versicolor) [104]. Imiquimod, an immune response modifier that stimulates cytotoxic T-cell-mediated responses through activation of toll-like receptors, leads to tumor destruction and depigmentation in lentigo-maligna lesions [105,106].…”