Metabolism and morphogenesis of human pathogenic fungi

人类病原真菌的代谢和形态建成

• 批准号: 5426828
• 负责人: Professor Dr. Matthias Brock
• 金额: --
• 依托单位: Fungal Biology Group
• 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 2005-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5426828?language=en
• 关键词: Metabolism; morphogenesis; human; pathogenic; fungi

Opportunistic human pathogenic fungi cause growing problems in transplantation medicine and therapy of AIDS patients. Only little is known about the way an infection is manifested and which determinants are essential to maintain and grow inside a host. Primary metabolism might play a major role and suppression of fungal metabolism seems to be a suitable target for drug development. However, care has to be taken to choose metabolic features, which are distinct from the hosts metabolism. Lysine is an essential amino acid for humans but can be generated de novo by fungi via the a-aminoadipic acid pathway. Therefore, our aim is to rule out the importance of lysine biosynthesis in development of an invasive aspergillosis mediated by Aspergillus fumigatus. We will investigate the role of different genes involved in lysine biosynthesis on the potential to cause an infection. Studies will involve macrophage assays and animal models in order to proof reduction of virulence. Another task will be the biochemical characterisation of selected enzymes, in order to obtain an idea about substrate specificity and potential inhibitors, insights, which might be useful in the development of new drugs for therapy.

人类病原真菌在移植医学和艾滋病治疗中的问题日益突出。关于感染的表现方式以及哪些决定因素对宿主体内的维持和生长至关重要，人们知之甚少。初级代谢可能发挥主要作用，抑制真菌代谢似乎是药物开发的合适目标。然而，必须注意选择代谢特征，这是从主机代谢不同。赖氨酸是人体必需的氨基酸，但可以通过α-氨基己二酸途径由真菌从头产生。因此，我们的目的是排除赖氨酸生物合成在烟曲霉介导的侵袭性曲霉病发展中的重要性。我们将研究参与赖氨酸生物合成的不同基因对引起感染的可能性的作用。研究将涉及巨噬细胞测定和动物模型，以证明毒力降低。另一项任务将是所选酶的生物化学表征，以获得有关底物特异性和潜在抑制剂的想法，这些想法可能有助于开发新的治疗药物。

项目成果

Evaluation of Lysine Biosynthesis as an Antifungal Drug Target: Biochemical Characterization of Aspergillus fumigatus Homocitrate Synthase and Virulence Studies

• DOI: 10.1128/ec.00020-10
• 发表时间: 2010-06-01
• 期刊: EUKARYOTIC CELL
• 作者: Schoebel, Felicitas;Jacobsen, Ilse D.;Brock, Matthias
• 通讯作者: Brock, Matthias