Aspergillus terreus as a cause of invasive aspergillosis: Impact of secondary metabolites on pathogenesis

从新兴的致病真菌Aspergillus terreus的培养提取物的口服应用导致肝细胞的形态变化，表明霉菌毒素的产生。因此，我们对侵袭性曲霉菌病小鼠感染模型的初步研究显示，感染曲霉菌的小鼠肝脏主要病变。terreus感染。虽然A.土曲霉菌在侵袭性曲霉病患者中的分离率低于曲霉菌。烟曲霉对强效抗真菌药物阿替西菌素B的耐药性阻碍了对A.感染并导致高达100%的死亡率。尽管A. terreus感染，发病机制几乎没有研究。阐明次生代谢产物的产生对A. terreus毒力，将建立感染模型，该模型允许通过使用生物发光A. terreus菌株。将使用涵盖所有次级代谢物生物合成簇的代表的微阵列将感染进展与次级代谢物产生相关联。报告菌株的使用将允许在体外条件下跟踪代谢产物的产生，以能够鉴定、纯化和表征相应的化合物。通过对次级代谢产物缺陷突变株毒力的研究，我们有望对A. terreus

Oral application of culture extracts from the emerging pathogenic fungus Aspergillus terreus causes morphological changes of liver cells, indicating the production of mycotoxins. Consistently, our preliminary investigations on murine infection models for invasive aspergillosis revealed major hepatic lesions in mice suffering from A. terreus infections. Although A. terreus is less frequently isolated from patients with invasive aspergillosis than A. fumigatus, the resistance against the potent antifungal drug amphotericin B hampers treatment of A. terreus infections and leads to up to 100% mortality. Despite the severe outcome of A. terreus infections, pathogenesis has hardly been studied. To elucidate the impact of the production of secondary metabolites on A. terreus virulence, infection models will be established, which allow monitoring the temporal and spatial development of the infection under in vivo conditions by using bioluminescent A. terreus strains. Microarrays covering representatives from all secondary metabolite biosynthesis clusters will be used to correlate the progression of infection with secondary metabolite production. The use of reporter strains will allow following the metabolite production under in vitro conditions to enable the identification, purification and characterisation of the respective compounds. By studying the virulence of mutants defective in secondary metabolite production we expect to gain new insights into the pathophysiology of A. terreus.