Novel molecular mechanisms of iron sensing and homeostasis in filamentous fungi

丝状真菌铁感应和稳态的新分子机制

• 批准号: 241377596
• 负责人: Professor Dr. Axel Brakhage, Ph.D.
• 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: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/241377596?language=en
• 关键词: Novel; molecular; mechanisms; iron; sensing

Iron is essential for numerous cellular processes but toxic in excess. Moreover, adaptation to iron starvation is a crucial virulence determinant of pathogens including fungi. Due to the fundamental differences in the mechanism employed by host and pathogens to maintain iron homeostasis, iron metabolism is an attractive new target for improvement of antifungal therapy and diagnosis of fungal infections. However, a better understanding of the molecular basis of fungal iron homeostasis is required.In various fungi including the most common airborne fungal pathogen Aspergillus fumigatus, the key iron regulator HapX has been shown to be required for adaptation to iron starvation via its interaction with the CCAAT-binding complex (CBC). Recently, we found that HapX is in addition essential for iron resistance, which underlines that HapX senses the cellular iron status to coordinate the transcriptional response.The planned collaborative studies by geneticists, biochemists and structural biologists aim to explore in molecular depth the functions of the HapX/CBC complex as iron sensor, transcriptional repressor and activator, as well as promoter organizer. In vivo and in vitro analyses are combined with structural examinations of the involved protein/protein and protein/DNA complexes to elucidate these novel regulatory mechanisms in eukaryotes.

铁对于众多细胞过程至关重要，但过量有毒。此外，适应铁饥饿是包括真菌在内的病原体的关键毒力决定因素。由于宿主和病原体维持铁稳态的机制的根本差异，铁代谢是改善抗真菌疗法和真菌感染诊断的有吸引力的新目标。然而，需要更好地了解真菌铁稳态的分子基础。最近，我们发现HAPX对于铁耐药性是必不可少的，它强调了HAPX感知细胞铁的状态以协调转录响应。遗传学家，生物化学家和结构生物学家的计划合作研究旨在以分子深度探索HAPX/CBC复杂的Iron Sensorter，Transcriptions，以及启动器，以及激进者，以及激进者，以及启动器，以及启动器，以及启动器。体内和体外分析与所涉及的蛋白质/蛋白质/DNA复合物的结构检查结合在一起，以阐明真核生物中这些新型调节机制。

项目成果

The monothiol glutaredoxin GrxD is essential for sensing iron starvation in Aspergillus fumigatus

• DOI: 10.1371/journal.pgen.1008379
• 发表时间: 2019-09-01
• 期刊: PLOS GENETICS
• 影响因子: 4.5
• 作者: Misslinger, Matthias;Scheven, Mareike Thea;Haas, Hubertus
• 通讯作者: Haas, Hubertus