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Abstract：
Endocytosis has been extensively studied in yeasts, where it plays crucial roles in growth, signaling regulation, and cell-surface receptor internalization. However, the biological functions of endocytosis in pathogenic filamentous fungi remain largely unexplored. In this study, we aimed to functionally characterize the roles of EdeA, an ortholog of the Saccharomyces cerevisiae endocytic protein Ede1, in Aspergillus fumigatus. EdeA was observed to be distributed as patches on the plasma membrane and concentrated in the subapical collar of hyphae, a localization characteristic of endocytic proteins. Loss of edeA caused defective hyphal polarity, reduced conidial production, and fewer sites of endocytosis initiations than that of the parental wild type. Notably, the edeA null mutant exhibited increased sensitivity to cell wall-disrupting agents, indicating a role for EdeA in maintaining cell wall integrity in A. fumigatus. This observation was further supported by the evidence showing that the thickness of the cell wall in the ΔedeA mutant increased, accompanied by abnormal activation of MpkA, a key component in the cell wall integrity pathway. Additionally, the ΔedeA mutant displayed increased pathogenicity in the Galleria mellonella wax moth infection model, possibly due to alterations in cell wall morphology. Site-directed mutagenesis identified the conserved residue E348 within the third EH (Eps15 homology) domain of EdeA as crucial for its subcellular localization and functions. In conclusion, our results highlight the involvement of EdeA in endocytosis, hyphal polarity, cell wall integrity, and pathogenicity in A. fumigatus.
OBJECTIVE: Aspergillus fumigatus is a significant human pathogenic fungus known to cause invasive aspergillosis, a disease with a high mortality rate. Understanding the basic principles of A. fumigatus pathogenicity is crucial for developing effective strategies against this pathogen. Previous research has underscored the importance of endocytosis in the infection capacity of pathogenic yeasts; however, its biological function in pathogenic mold remains largely unexplored. Our characterization of EdeA in A. fumigatus sheds light on the role of endocytosis in the development, stress response, and pathogenicity of pathogenic molds. These findings suggest that the components of the endocytosis process may serve as potential targets for antifungal therapy.
OBJECTIVE: Aspergillus fumigatus is a significant human pathogenic fungus known to cause invasive aspergillosis, a disease with a high mortality rate. Understanding the basic principles of A. fumigatus pathogenicity is crucial for developing effective strategies against this pathogen. Previous research has underscored the importance of endocytosis in the infection capacity of pathogenic yeasts; however, its biological function in pathogenic mold remains largely unexplored. Our characterization of EdeA in A. fumigatus sheds light on the role of endocytosis in the development, stress response, and pathogenicity of pathogenic molds. These findings suggest that the components of the endocytosis process may serve as potential targets for antifungal therapy.
摘要：
胞吞作用在酵母中得到了广泛的研究,它在增长中起着至关重要的作用，信令调节，和细胞表面受体内化。然而,致病性丝状真菌内吞作用的生物学功能仍未被研究。在这项研究中,我们的目的是在功能上描述EdeA的作用，烟曲霉中酿酒酵母内吞蛋白Ede1的直系同源物。观察到EdeA以斑块形式分布在质膜上，并集中在菌丝的根尖下领中，内吞蛋白的定位特征。edeA丢失导致菌丝极性缺陷，减少分生孢子的产生，内吞起始位点少于亲本野生型。值得注意的是,edeAnull突变体对细胞壁破坏剂的敏感性增加，表明EdeA在维持烟曲霉细胞壁完整性中的作用。这一观察进一步得到了证据的支持，这些证据表明ΔedeA突变体的细胞壁厚度增加，伴随着MpkA的异常激活，细胞壁完整性途径的关键组成部分。此外,ΔedeA突变体在Galleriamelonella蜡蛾感染模型中显示出增加的致病性，可能是由于细胞壁形态的改变。定点诱变鉴定了EdeA的第三个EH（Eps15同源性）结构域内的保守残基E348对于其亚细胞定位和功能至关重要。总之,我们的结果强调了EdeA参与内吞作用，菌丝极性，细胞壁完整性，以及烟曲霉的致病性。
目的：烟曲霉是一种重要的人类病原真菌，已知可引起侵袭性曲霉病，一种高死亡率的疾病。了解烟曲霉致病性的基本原理对于开发针对该病原体的有效策略至关重要。先前的研究强调了内吞作用在致病性酵母感染能力中的重要性；然而，其在致病霉菌中的生物学功能仍未被探索。我们对烟曲霉中EdeA的表征揭示了内吞作用在发育中的作用，应激反应，和致病霉菌的致病性。这些发现表明，内吞过程的组成部分可能是抗真菌治疗的潜在目标。
目的：烟曲霉是一种重要的人类病原真菌，已知可引起侵袭性曲霉病，一种高死亡率的疾病。了解烟曲霉致病性的基本原理对于开发针对该病原体的有效策略至关重要。先前的研究强调了内吞作用在致病性酵母感染能力中的重要性；然而，其在致病霉菌中的生物学功能仍未被探索。我们对烟曲霉中EdeA的表征揭示了内吞作用在发育中的作用，应激反应，和致病霉菌的致病性。这些发现表明，内吞过程的组成部分可能是抗真菌治疗的潜在目标。
