Pathogenicity factors of Malassezia furfur: genetic regulation of tryptophan-dependent secondary metabolites and their effect on immunocompetent and structural cells of human skin

• Applicant: Professor Dr. Bernhard Hube
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2004 to 2007
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5429315

Malassezia yeasts can produce pigments and fluorochromes if tryptophan is offered as the main nitrogen source. This newly discovered metabolic pathway may explain clinical phenomena of pityriasis versicolor (PV), a common Malassezia-related skin disease. To date, 18 compounds have been isolated, of which 14 are new in terms of chemical structure. They have interesting pharmacological properties, such as UV protection (pityriacitrin, pityrialacton), stimulus-specific inhibition of the oxidative burst of granulocytes and IL12p70 release of dendritic cells (pityriarubins), induction of apoptosis in human melanocytes and activation of the arylhydrocarbon receptor as well as induction of cytochrome P450 in keratinocytes (malassezin), properties that are closely associated with clinical signs of PV. The mechanism and profile of action are to be further characterized by means of bioassays. Apart from a possible apoptosis induction in melanoma cells, the effect of individual secondary metabolites on dendritic and mononuclear cells and the mechanism of stimulus-specific burst inhibition are to be clarified in more detail. To investigate the gene expression in keratinocytes, fibroblasts and melanocytes, the secondary metabolites will be used in a skin-specific screening cDNA microarray. Genes of Malassezia yeasts that are involved in pigment synthesis will be identified by means of cDNA subtraction techniques. By demonstration of the corresponding transcripts in skin samples of patients with pityriasis versicolor the relevance of the identified genes in this disease is to be investigated.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1160: Colonisation and Infection by Human-pathogenic Fungi