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The Putative APSES Transcription Factor RgdA Governs Growth, Development, Toxigenesis, and Virulence in Aspergillus fumigatus.


ABSTRACT: 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 ?rgdA mutant compared to those in the wild type (WT). Moreover, ?rgdA 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 ?rgdA mutant. Comparative transcriptomic analyses revealed that the ?rgdA mutant showed higher mRNA levels of gliotoxin (GT)-biosynthetic genes and GT production. While the ?rgdA mutant exhibited elevated production of GT, ?rgdA 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 ?rgdA mutant. In summary, RgdA plays multiple roles in governing growth, development, GT production, and virulence which may involve attenuation of PKA and SakA signaling.IMPORTANCE Immunocompromised patients are susceptible to infections with the opportunistic human-pathogenic fungus Aspergillus fumigatus This fungus causes systemic infections such as invasive aspergillosis (IA), which is one of the most life-threatening fungal diseases. To control this serious disease, it is critical to identify new antifungal drug targets. In fungi, the transcriptional regulatory proteins of the APSES family play crucial roles in controlling various biological processes, including mating, asexual sporulation and dimorphic growth, and virulence traits. This study found that a putative APSES transcription factor, RgdA, regulates normal growth, asexual development, conidium germination, spore wall architecture and hydrophobicity, toxin production, and virulence in A. fumigatus Better understanding the molecular mechanisms of RgdA in human-pathogenic fungi may reveal a novel antifungal target for future drug development.

SUBMITTER: Jun SC 

PROVIDER: S-EPMC7657592 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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The Putative APSES Transcription Factor RgdA Governs Growth, Development, Toxigenesis, and Virulence in Aspergillus fumigatus.

Jun Sang-Cheol SC   Choi Yong-Ho YH   Lee Min-Woo MW   Yu Jae-Hyuk JH   Shin Kwang-Soo KS  

mSphere 20201111 6


The APSES transcription factor (TF) in <i>Aspergillus</i> species is known to govern diverse cellular processes, including growth, development, and secondary metabolism. Here, we investigated functions of the <i>rgdA</i> gene (Afu3g13920) encoding a putative APSES TF in the opportunistic human-pathogenic fungus <i>Aspergillus fumigatus</i> The <i>rgdA</i> deletion resulted in significantly decreased hyphal growth and asexual sporulation. Consistently, transcript levels of the key asexual develop  ...[more]

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