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

糠秕马拉色菌的致病因素：色氨酸依赖性次级代谢产物的基因调控及其对人体皮肤免疫活性细胞和结构细胞的影响

• 批准号: 5429315
• 负责人: Professor Dr. Bernhard Hube
• 金额: --
• 依托单位: Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. Hans-Knöll-Institut
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2004
• 资助国家: 德国
• 起止时间: 2003-12-31 至 2006-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5429315?language=en
• 关键词: Pathogenicity; factors; Malassezia; furfur; genetic

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.

如果提供色氨酸作为主要氮源，马拉色酵母可以产生色素和荧光染料。这一新发现的代谢途径可以解释花斑癣（PV）的临床现象，这是一种常见的马拉色菌相关皮肤病。迄今为止，已分离出18种化合物，其中14种化学结构是新的。它们具有有趣的药理学特性，例如紫外线防护（糠秕苷、糠秕内酯）、对粒细胞氧化爆发的刺激特异性抑制和树突状细胞的 IL12p70 释放（糠秕红素）、诱导人黑素细胞凋亡、激活芳基烃受体以及诱导细胞色素 角质形成细胞中的 P450（马拉色津），其特性与真性红斑狼疮的临床症状密切相关。其机制和作用概况将通过生物测定进一步表征。除了可能诱导黑色素瘤细胞凋亡之外，单个次级代谢产物对树突状细胞和单核细胞的影响以及刺激特异性爆发抑制的机制还有待更详细地阐明。为了研究角质形成细胞、成纤维细胞和黑素细胞中的基因表达，次级代谢物将用于皮肤特异性筛选 cDNA 微阵列。马拉色酵母中参与色素合成的基因将通过 cDNA 消减技术进行鉴定。通过证明花斑癣患者皮肤样本中的相应转录本，将研究已识别基因与该疾病的相关性。