Fungal morphogenesis and environmental response

真菌形态发生和环境响应

• 批准号: 203696-2013
• 负责人: Kaminskyj, Susan
• 金额: $ 2.62万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=655030
• 关键词: Fungal; morphogenesis; environmental; response

Aspergillus, a mould, is an asexual fungus that impacts humanity for good and ill. Some species are used in biotechnology, but many are also opportunistic human pathogens causing morbid disease. Filamentous fungal cells, called hyphae, are surrounded, supported, and protected by cell walls that enable them to penetrate and explore their surroundings in search of nutrients. Hyphae are tubular and grow only at their tips, where they secrete wall-forming materials. The hyphal wall forms a porous interface between the cell and its environment. Wall composition, structure and function are inter-dependent. As in all fungi, the Aspergillus wall is ~85% carbohydrate, mostly types not found in animals. Wall biosynthesis pathways can be anti-fungal drug targets.** Interaction between wall components is key to wall structure-function, but despite >60 years of study, much remains unknown. It is notable that fungi respond to environmental change, e.g. drugs, through cell wall integrity network regulation, and it is this regulation of cell wall integrity that is a focus of research in my laboratory. As an example, galactofuranose (Gal-f) is a minor [~5%] wall sugar that decorates wall proteins. We have shown that deleting any of three steps in Gal-f biosynthesis causes major defects in wall structure-function, including: 500-fold lower hyphal growth rate and spore production; soft, thick and abnormal cell walls; and hyperbranching. However, reduced Gal-f is partly compensated for by higher content of other, co-regulated wall components, such as alpha-glucans, whose roles are yet to be understood. We have found that deletion of genes for alpha-glucan production does not result in an obvious change in appearance, or phenotype, on a solid medium, but may result in colony fragmentation in a shaken liquid medium.** In the next funding cycle, we will characterize alpha-glucan synthesis in Aspergillus, and explore relationships between wall biosynthesis pathways. Urgency is called for, as we have shown that Aspergillus can develop heritable resistance to wall-targeting drugs in under a week. We have already identified novel wall-synthesis genes using this strategy, and will extend efforts in this critically important area of research.**************************

曲霉菌，一种霉菌，是一种无性真菌，对人类的影响有好有坏。有些物种被用于生物技术，但许多也是机会主义的人类病原体，导致病态疾病。 丝状真菌细胞，称为菌丝，被细胞壁包围，支持和保护，使它们能够穿透并探索周围环境以寻找营养物质。菌丝是管状的，只在顶端生长，在那里它们分泌形成壁的物质。菌丝壁在细胞和其环境之间形成多孔界面。壁的组成、结构和功能是相互依赖的。与所有真菌一样，曲霉菌壁约85%是碳水化合物，大多数类型在动物中没有发现。细胞壁生物合成途径可以成为抗真菌药物的靶点。 墙体构件之间的相互作用是墙体结构功能的关键，但尽管经过60多年的研究，仍有许多未知之处。 值得注意的是，真菌通过细胞壁完整性网络调节来响应环境变化，例如药物，并且正是这种细胞壁完整性的调节是我实验室的研究重点。例如，呋喃半乳糖（Gal-f）是修饰壁蛋白的次要[~5%]壁糖。我们已经表明，删除Gal-f生物合成中的三个步骤中的任何一个都会导致壁结构-功能的重大缺陷，包括：菌丝生长速率和孢子产生降低500倍;软，厚和异常的细胞壁;和超支化。然而，减少的Gal-f部分地被更高含量的其他共同调节的壁组分（例如α-葡聚糖）所补偿，其作用尚不清楚。我们发现，α-葡聚糖生产基因的缺失不会导致固体培养基上的外观或表型发生明显变化，但可能导致振荡液体培养基中的菌落破碎。** 在下一个资助周期中，我们将描述曲霉菌中α-葡聚糖的合成，并探索细胞壁生物合成途径之间的关系。 迫切需要，因为我们已经表明曲霉菌可以在不到一周的时间内对靶向药物产生遗传性耐药性。 我们已经使用这种策略确定了新的细胞壁合成基因，并将在这一至关重要的研究领域继续努力。