Fungal morphogenesis and environmental response

点击翻译按钮获取中文摘要

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.