4.7 Article

Characterization of the mbsA Gene Encoding a Putative APSES Transcription Factor in Aspergillus fumigatus

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出版社

MDPI
DOI: 10.3390/ijms22073777

关键词

APSES transcription factor; Aspergillus fumigatus; MbsA; rodlet layer; gliotoxin; virulence; transcriptomics

资金

  1. National Research Foundation of Korea (NRF) - Korea government (MOE) [2020R111A3051661, 2020R1A6A3A13053167]
  2. National Research Foundation of Korea [2020R1A6A3A13053167] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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The deletion of the mbsA gene in Aspergillus fumigatus results in impaired growth and sporulation, altered spore wall structure, increased gliotoxin production but reduced virulence, potentially due to defects in the SakA signaling pathway.
The APSES family proteins are transcription factors (TFs) with a basic helix-loop-helix domain, known to regulate growth, development, secondary metabolism, and other biological processes in Aspergillus species. In the genome of the human opportunistic pathogenic fungus Aspergillus fumigatus, five genes predicted to encode APSES TFs are present. Here, we report the characterization of one of these genes, called mbsA (Afu7g05620). The deletion (Delta) of mbsA resulted in significantly decreased hyphal growth and asexual sporulation (conidiation), and lowered mRNA levels of the key conidiation genes abaA, brlA, and wetA. Moreover, Delta mbsA resulted in reduced spore germination rates, elevated sensitivity toward Nikkomycin Z, and significantly lowered transcripts levels of genes associated with chitin synthesis. The mbsA deletion also resulted in significantly reduced levels of proteins and transcripts of genes associated with the SakA MAP kinase pathway. Importantly, the cell wall hydrophobicity and architecture of the Delta mbsA asexual spores (conidia) were altered, notably lacking the rodlet layer on the surface of the Delta mbsA conidium. Comparative transcriptomic analyses revealed that the Delta mbsA mutant showed higher mRNA levels of gliotoxin (GT) biosynthetic genes, which was corroborated by elevated levels of GT production in the mutant. While the Delta mbsA mutant produced higher amount of GT, Delta mbsA strains showed reduced virulence in the murine model, likely due to the defective spore integrity. In summary, the putative APSES TF MbsA plays a multiple role in governing growth, development, spore wall architecture, GT production, and virulence, which may be associated with the attenuated SakA signaling pathway.

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