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The Putative APSES Transcription Factor RgdA Governs Growth, Development, Toxigenesis, and Virulence in Aspergillus fumigatus
mSphere ( IF 3.7 ) Pub Date : 2020-11-11 , DOI: 10.1128/msphere.00998-20
Sang-Cheol Jun 1 , Yong-Ho Choi 1 , Min-Woo Lee 2 , Jae-Hyuk Yu 3, 4 , Kwang-Soo Shin 5
Affiliation  

The APSES transcription factor (TF) in Aspergillus species is known to govern diverse cellular processes, including growth, development, and secondary metabolism. Here, we investigated functions of the rgdA gene (Afu3g13920) encoding a putative APSES TF in the opportunistic human-pathogenic fungus Aspergillus fumigatus. The rgdA deletion resulted in significantly decreased hyphal growth and asexual sporulation. Consistently, transcript levels of the key asexual developmental regulators abaA, brlA, and wetA were decreased in the ΔrgdA mutant compared to those in the wild type (WT). Moreover, ΔrgdA resulted in reduced spore germination rates and elevated transcript levels of genes associated with conidium dormancy. The conidial cell wall hydrophobicity and architecture were changed, and levels of the RodA protein were decreased in the ΔrgdA mutant. Comparative transcriptomic analyses revealed that the ΔrgdA mutant showed higher mRNA levels of gliotoxin (GT)-biosynthetic genes and GT production. While the ΔrgdA mutant exhibited elevated production of GT, ΔrgdA strains showed reduced virulence in the mouse model. In addition, mRNA levels of genes associated with the cyclic AMP (cAMP)-protein kinase A (PKA) signaling pathway and the SakA mitogen-activated protein (MAP) kinase pathway were increased in the ΔrgdA mutant. In summary, RgdA plays multiple roles in governing growth, development, GT production, and virulence which may involve attenuation of PKA and SakA signaling.

中文翻译:

假定的 APSES 转录因子 RgdA 控制烟曲霉的生长、发育、产毒和毒力

已知曲霉属物种中的 APSES 转录因子 (TF)控制着多种细胞过程,包括生长、发育和次级代谢。在这里,我们研究了rgdA基因 (Afu3g13920) 在机会性人类致病真菌烟曲霉中编码推定 APSES TF 的功能。该rgdA缺失导致显著下跌菌丝生长和无性孢子。一致地,与野生型 (WT) 中的那些相比,Δ rgdA突变体中关键无性发育调节因子abaAbrlAwetA 的转录水平降低。此外,ΔrgdA导致孢子萌发率降低和与分生孢子休眠相关的基因转录水平升高。Δ rgdA突变体中分生孢子细胞壁的疏水性和结构发生了变化,并且 RodA 蛋白的水平降低。比较转录组学分析显示,Δ rgdA突变体显示出较高的胶质毒素 (GT) 生物合成基因和 GT 产生的 mRNA 水平。虽然 Δ rgdA突变体表现出 GT 产量增加,但 Δ rgdA菌株在小鼠模型中表现出降低的毒力。另外,与环AMP(cAMP)相关联的基因的mRNA水平-蛋白激酶A(PKA)的信号传导途径和阪促分裂原活化蛋白(MAP)激酶途径的Δ分别增加rgdA突变体。总之,RgdA 在调控生长、发育、GT 产生和毒力方面发挥多种作用,这可能涉及 PKA 和 SakA 信号传导的减弱。
更新日期:2020-11-12
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