Wei Qian, He Cong, Peng Xinyuan, An Bingyi, Peng Min, Wang Xiaoyu, Zhang Chen, Lu Ling, Sang Hong, Kong Qingtao
Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Department of Dermatology, People's Liberation Army the General Hospital of Western Theater Command, Chengdu, China.
World J Microbiol Biotechnol. 2024 Dec 30;41(1):19. doi: 10.1007/s11274-024-04234-1.
The majority of Aspergillus fumigatus reproduction occurs asexually, with large numbers of conidiophores producing small hydrophobic conidia dispersed aerially. When healthy hosts inhale conidia, the mucosal cilia and phagocytosis by the innate immune system can remove them. However, in immunocompromised hosts, the conidia are not removed, which allows them to germinate, forming mycelium that invades host tissues and causes disease. Previously we isolated a white A. fumigatus A1j strain incapable of producing conidia and screened several genes (including dopA) with significant expression differences and mutant loci in A1j. DopA homologous proteins in other species have been partially studied and are known to participate in various membrane transport-related cellular functions. Defects in these proteins in Saccharomyces cerevisiae, Caenorhabditis elegans, and Aspergillus nidulans result in defective cell morphology and abnormal growth. In this study, we observed reduced conidia production and abnormal development of spore-producing structures in the A. fumigatus dopA null strain, compared to parental strain, and demonstrated that dopA also modulates stress response and virulence of A. fumigatus.
烟曲霉的繁殖大多通过无性方式进行，大量分生孢子梗产生的小型疏水分生孢子通过空气传播。当健康宿主吸入分生孢子时，黏膜纤毛和固有免疫系统的吞噬作用可将其清除。然而，在免疫功能低下的宿主中，分生孢子无法被清除，从而使其得以萌发，形成侵入宿主组织并引发疾病的菌丝体。此前我们分离出了一株无法产生分生孢子的白色烟曲霉A1j菌株，并筛选了几个在A1j中具有显著表达差异和突变位点的基因（包括dopA）。其他物种中的DopA同源蛋白已得到部分研究，已知其参与各种与膜转运相关的细胞功能。酿酒酵母、秀丽隐杆线虫和构巢曲霉中这些蛋白的缺陷会导致细胞形态缺陷和生长异常。在本研究中，我们观察到与亲本菌株相比，烟曲霉dopA基因缺失菌株的分生孢子产量降低，产孢结构发育异常，并证明dopA还可调节烟曲霉对应激的反应及毒力。
