Laboratory of Yeast Systematics, Tokyo NODAI Research Institute, Tokyo University of Agriculture, Setagaya, Tokyo, Japan.
Department of Molecular Microbiology, Faculty of Life Sciences, Tokyo University of Agriculture, Setagaya, Tokyo, Japan.
Microbiol Spectr. 2023 Jun 15;11(3):e0424222. doi: 10.1128/spectrum.04242-22. Epub 2023 Apr 27.
Fungal dimorphism involves two morphologies: a unicellular yeast cell and a multicellular hyphal form. Invasion of hyphae into human cells causes severe opportunistic infections. The transition between yeast and hyphal forms is associated with the virulence of fungi; however, the mechanism is poorly understood. Therefore, we aimed to identify factors that induce hyphal growth of Trichosporon asahii, a dimorphic basidiomycete that causes trichosporonosis. T. asahii showed poor growth and formed small cells containing large lipid droplets and fragmented mitochondria when cultivated for 16 h in a nutrient-deficient liquid medium. However, these phenotypes were suppressed via the addition of yeast nitrogen base. When T. asahii cells were cultivated in the presence of different compounds present in the yeast nitrogen base, we found that magnesium sulfate was a key factor for inducing cell elongation, and its addition dramatically restored hyphal growth in T. asahii. In T. asahii hyphae, vacuoles were enlarged, the size of lipid droplets was decreased, and mitochondria were distributed throughout the cell cytoplasm and adjacent to the cell walls. Additionally, hyphal growth was disrupted due to treatment with an actin inhibitor. The actin inhibitor latrunculin A disrupted the mitochondrial distribution even in hyphal cells. Furthermore, magnesium sulfate treatment accelerated hyphal growth in T. asahii for 72 h when the cells were cultivated in a nutrient-deficient liquid medium. Collectively, our results suggest that an increase in magnesium levels triggers the transition from the yeast to hyphal form in T. asahii. These findings will support studies on the pathogenesis of fungi and aid in developing treatments. Understanding the mechanism underlying fungal dimorphism is crucial to discern its invasion into human cells. Invasion is caused by the hyphal form rather than the yeast form; therefore, it is important to understand the mechanism of transition from the yeast to hyphal form. To study the transition mechanism, we utilized Trichosporon asahii, a dimorphic basidiomycete that causes severe trichosporonosis since there are fewer studies on T. asahii than on ascomycetes. This study suggests that an increase in Mg, the most abundant mineral in living cells, triggers growth of filamentous hyphae and increases the distribution of mitochondria throughout the cell cytoplasm and adjacent to the cell walls in T. asahii. Understanding the mechanism of hyphal growth triggered by Mg increase will provide a model system to explore fungal pathogenicity in the future.
单细胞酵母细胞和多细胞菌丝形式。菌丝侵入人体细胞会导致严重的机会性感染。酵母和菌丝形式之间的转变与真菌的毒力有关；然而，其机制尚不清楚。因此，我们旨在鉴定诱导出芽红酵母（一种引起毛孢子菌病的二态担子菌）菌丝生长的因素。当在营养缺乏的液体培养基中培养 16 小时时，出芽红酵母表现出较差的生长，形成含有大脂质滴和碎片化线粒体的小细胞。然而，通过添加酵母氮基可以抑制这些表型。当在存在酵母氮基中存在的不同化合物的情况下培养出芽红酵母细胞时，我们发现硫酸镁是诱导细胞伸长的关键因素，其添加极大地恢复了出芽红酵母的菌丝生长。在出芽红酵母菌丝中，液泡增大，脂质滴的大小减小，线粒体分布在整个细胞质和细胞壁附近。此外，由于用肌动蛋白抑制剂处理，菌丝生长受到破坏。肌动蛋白抑制剂 latrunculin A 甚至在菌丝细胞中破坏了线粒体的分布。此外，当在营养缺乏的液体培养基中培养细胞时，硫酸镁处理在 72 小时内加速了出芽红酵母的菌丝生长。总的来说，我们的结果表明镁水平的增加触发了出芽红酵母从酵母到菌丝形式的转变。这些发现将支持真菌发病机制的研究，并有助于开发治疗方法。
理解真菌二态性的机制对于辨别其侵入人体细胞至关重要。入侵是由菌丝形式而不是酵母形式引起的；因此，理解从酵母到菌丝形式的转变机制很重要。为了研究转变机制，我们利用了出芽红酵母，这是一种引起严重毛孢子菌病的二态担子菌，因为关于出芽红酵母的研究比关于子囊菌的研究少。本研究表明，活细胞中最丰富的矿物质镁的增加触发了丝状菌丝的生长，并增加了线粒体在细胞质中的分布和细胞壁附近。理解镁增加引发的菌丝生长机制将为未来探索真菌致病性提供一个模型系统。
