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

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 species. In the genome of the human opportunistic pathogenic fungus , five genes predicted to encode APSES TFs are present. Here, we report the characterization of one of these genes, called (Afu7g05620). The deletion (Δ) of resulted in significantly decreased hyphal growth and asexual sporulation (conidiation), and lowered mRNA levels of the key conidiation genes , and . Moreover, Δ resulted in reduced spore germination rates, elevated sensitivity toward Nikkomycin Z, and significantly lowered transcripts levels of genes associated with chitin synthesis. The 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 Δ asexual spores (conidia) were altered, notably lacking the rodlet layer on the surface of the Δ conidium. Comparative transcriptomic analyses revealed that the Δ mutant showed higher mRNA levels of gliotoxin (GT) biosynthetic genes, which was corroborated by elevated levels of GT production in the mutant. While the Δ mutant produced higher amount of GT, Δ 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.