Metabolism and morphogenesis of human pathogenic fungi

机会性人类致病真菌在艾滋病患者的移植、医学和治疗方面造成了越来越多的问题。关于感染是如何表现出来的，以及哪些决定因素是维持和在宿主体内生长所必需的，人们知之甚少。初级代谢可能起主要作用，抑制真菌代谢似乎是药物开发的合适靶点。然而，必须注意选择不同于宿主代谢的代谢特征。赖氨酸是人体必需的氨基酸，但可由真菌通过a-氨基己二酸途径从头产生。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生中的重要性。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分析和动物模型，以证明毒力降低。另一项任务将是选定酶的生化特性，以获得关于底物特异性和潜在的抑制剂的想法，这可能对开发治疗新药有用。

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.