Novel Biological Functions of the NsdC Transcription Factor in Aspergillus fumigatus.
Novel Biological Functions of the NsdC Transcription Factor in Aspergillus fumigatus.
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DOI：
10.1128/mbio.03102-20
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发表时间：
2021-01-05
期刊：
影响因子：
6.4
通讯作者：
Goldman GH
中科院分区：
文献类型：
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作者：
Alves de Castro P;Valero C;Chiaratto J;Colabardini AC;Pardeshi L;Pereira Silva L;Almeida F;Campos Rocha M;Nascimento Silva R;Malavazi I;Du W;Dyer PS;Brock M;Vieira Loures F;Wong KH;Goldman GH
真菌锌指转录因子NsdC以其在有性生殖（而不是性发育）中的重要作用而命名，并且最为人所知。在以往对细粒曲霉的研究中，它也被证明具有促进营养生长和抑制无性繁殖的作用。本研究研究了nsdC同源物在人类条件致病菌烟熏假单胞菌中的作用。NsdC再次被发现对性发育至关重要，在一个杂交的MAT1-1和MAT1-2交配伴侣中缺失NsdC基因会导致完全丧失生育能力。然而，在一个交配伴侣中有一个nsdC的功能拷贝就足以进行有性繁殖。nsdC的缺失也导致营养生长下降，并允许液体培养中的分生，再次与先前的发现一致。然而，烟曲霉的NsdC具有其他生物学功能，包括对钙胁迫的响应、细胞壁结构的正确组织以及对细胞壁应激源的响应。此外，毒力和宿主免疫识别也受到影响。RNA聚合酶II （PolII）的染色质免疫沉淀（ChIP）和下一代测序（Seq）的基因表达研究显示，在基础生长条件下，nsdC的缺失导致620多个基因的表达变化。这表明该转录因子介导多种信号和代谢途径的活性，并表明尽管该基因被命名，但促进有性生殖只是NsdC的多种作用之一。
The fungal zinc finger transcription factor NsdC is named after, and is best known for, its essential role in sexual reproduction (never in sexual development). In previous studies with Aspergillus nidulans, it was also shown to have roles in promotion of vegetative growth and suppression of asexual conidiation. In this study, the function of the nsdC homologue in the opportunistic human pathogen A. fumigatus was investigated. NsdC was again found to be essential for sexual development, with deletion of the nsdC gene in both MAT1-1 and MAT1-2 mating partners of a cross leading to complete loss of fertility. However, a functional copy of nsdC in one mating partner was sufficient to allow sexual reproduction. Deletion of nsdC also led to decreased vegetative growth and allowed conidiation in liquid cultures, again consistent with previous findings. However, NsdC in A. fumigatus was shown to have additional biological functions including response to calcium stress, correct organization of cell wall structure, and response to the cell wall stressors. Furthermore, virulence and host immune recognition were affected. Gene expression studies involving chromatin immunoprecipitation (ChIP) of RNA polymerase II (PolII) coupled to next-generation sequencing (Seq) revealed that deletion of nsdC resulted in changes in expression of over 620 genes under basal growth conditions. This demonstrated that this transcription factor mediates the activity of a wide variety of signaling and metabolic pathways and indicates that despite the naming of the gene, the promotion of sexual reproduction is just one among multiple roles of NsdC.