The article presents virulence factors of Malassezia yeasts ranging from irritant metabolic byproducts to highly bioactive indole derivatives and attempts to clarify their pathogenic implications in the different diseases. Special emphasis is given to the pathogenesis of pityriasis versicolor, as it represents the disease wherein the causative relationship with Malassezia yeasts appears the most obvious.
In atopic dermatitis, microbial allergens may be pathogenetically significant. Apart from Staphyloccocus aureus, these are primarily lipophilic Malassezia yeasts. They are particularly involved in the pathogenesis of head and neck dermatitis (HND), a special form of atopic dermatitis, which is often difficult to treat. Fifty patients (21 men, 29 women) with moderate to severe HND of at least 6 months’ duration were included in a prospective double-blind study. All of them showed at least 10% involvement of the head-neck region. The severity of disease was evaluated by Investigator Global Assessment (IGA), Eczema Area and Severity Index (EASI) for the head-neck region and a pruritus score. IgE antibodies to Malassezia sympodialis and/or Malassezia furfur (at least CAP class 1) were a prerequisite for study enrollment. Either 1% ciclopiroxolamine cream (Batrafen; Aventis Pharma, Bad Soden, Germany) or the corresponding base cream were thinly applied to the affected areas twice daily for 28 days. Sixteen patients in the ciclopiroxolamine group and 13 patients in the placebo group completed the study. To assess the change in severity of atopic eczema, IGA differences between the individual measuring points were determined for all patients. There were significant differences in the IGA score change between the ciclopiroxolamine group and the placebo group, from t3 to t4, and over the total period. Similar, but not significant, changes were observed with the EASI score, in terms of affected skin area and itching. The present study is the first to examine the effect of antifungal single-drug therapy with a cream containing ciclopiroxolamine on the course of HND. The study medication was found to be significantly effective. To optimize this effect, suitable patients selected in terms of fungal load, specific IgE, prick test and particularly atopy patch test for Malassezia antigens could receive combined treatment with antimycotic-containing shampoos and/ or short-term systemic antimycotic therapy in severe cases.
In Malassezia furfur, tryptophan as the main nitrogen source induces production of the potent ultraviolet-absorbing indole compound pityriacitrin. An in vitro study about the effects of pityriacitrin on other human skin microorganisms is presented, with special focus on Candida albicans and staphylococci in which its toxicity and UV-protective capacity were investigated. Candida albicans was irradiated with UVB light either in the presence or in the absence of pityriacitrin (11 mmol) and the growth rate was determined. A UVB dose of 1 J cm(-2) caused death of the fungi without pityriacitrin, whereas those in the presence of pityriacitrin showed almost unaffected growth. A diffusion test in staphylococci revealed no antibiotic effects of pityriacitrin. For testing of an ultraviolet-protective effect, staphylococci were either inoculated and irradiated in a plate model for visual assessment of growth or inoculated and irradiated in square quartz cylinders for quantitative measurement of cell density, each time in the absence or presence of pityriacitrin. Cell density of the bacterial suspensions exhibited nearly no influence of pityriacitrin on growth rates, while again a UV-protective effect was observed. In summary, pityriacitrin has an ultraviolet-protective effect on Candida albicans and staphylococci with no toxicity in the range tested.
Malassezia species are associated with pityriasis versicolor (PV) and its depigmented variant pityriasis versicolor alba (PVa), widespread fungal skin infections in humans. The pathogenesis of PV and PVa remains unclear, including their clinical and histological symptoms such as hyper- and depigmentation, reduced responsiveness to ultraviolet radiation and lack of inflammatory reaction despite high fungal load. Pigments produced by M. furfur are possibly involved in the pathogenesis of PV. In vitro, M. furfur produces a wide range of pigments and fluorochromes when cultured with tryptophan as the sole nitrogen source. We have begun to analyse the molecular basis of pigment production by searching for genes associated with tryptophan-based pigment production. A suppression subtractive hybridization (SSH) protocol was used to identify genes expressed in M. furfur cells producing pigments, but not in non-induced cells. SSH was performed 3 and 5 h after onset of pigment induction. Up-regulation of genes in the pigment-producing cells was confirmed by reverse northern analysis. More than 1,500 cDNA sequences of both the indicated time points were analysed. We identified a wide variety of genes associated with metabolism and several genes with unknown function are specifically expressed during pigment production. Furthermore, a fraction of genes possibly involved in different steps of the newly discovered indolic pathway of M. furfur were expressed in pigment producing cells. These data provide the first molecular insight into pigment production of M. furfur.
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