Carbon- and nitrogen utilisation of pathogenic Candida and Aspergillus species during pathogenesis

寄生性人类病原性真菌在免疫功能低下的患者中引起越来越多的问题。虽然对碳和氮代谢的了解可能会导致新的抗真菌药物的开发，但对这些真菌在发病过程中的代谢要求知之甚少。白色念珠菌需要一个功能性的乙醛酸循环来获得完整的毒力，脂质代谢被认为是致病的关键。由于乙醛酸循环是烟曲霉毒力的关键，本项目的一个目的是阐明这两种重要的医学真菌之间的代谢差异。因此，我们想研究这些真菌在体内条件下利用的营养物质以及它们是如何被利用的。这些研究将涉及2-D凝胶分析和体外生长条件下的转录组学以及感染组织内的单细胞分析，以研究感染条件下特定代谢途径的重要性。此外，我们还将对在发病过程中特异性上调的酶进行生物化学研究，以确定抗真菌治疗和诊断的新靶点。

Opportunistic human pathogenic fungi cause growing problems in immunocompromised patients. Little is known about the metabolic requirements of these fungi during pathogenesis although the understanding of carbon- and nitrogen metabolism could lead to the development of new antifungal drugs. Candida albicans requires a functional glyoxylate cycle for full virulence and lipid metabolism was assumed to be essential for pathogenesis. Since the glyoxylate cycle is dispensable for virulence of Aspergillus fumigatus, one aim of this project is to elucidate the metabolic differences between these two medically important fungi. Therefore, we want to study the nutrients utilised by these fungi under in vivo conditions and how they are made available. These studies will involve 2-D gel analyses and transcriptomics from in vitro growth conditions as well as single cell profiling within infected tissues to study the importance of specific metabolic pathways under infectious conditions. Furthermore, we will biochemically characterise enzymes, which turn out to be specifically upregulated during pathogenesis to identify new targets for antifungal therapy and diagnosis.