Functional Characterization of the GNAT Family Histone Acetyltransferase Elp3 and GcnE in Aspergillus fumigatus

Int J Mol Sci. 2023 Jan 22;24(3):2179. doi: 10.3390/ijms24032179.

Abstract

Post-translational modifications of chromatin structure by histone acetyltransferase (HATs) play a pivotal role in the regulation of gene expression and diverse biological processes. However, the function of GNAT family HATs, especially Elp3, in the opportunistic human pathogenic fungus Aspergillus fumigatus is largely unknown. To investigate the roles of the GNAT family HATs Elp3 and GcnE in the A. fumigatus, we have generated and characterized individual null Δelp3 and ΔgcnE mutants. The radial growth of fungal colonies was significantly decreased by the loss of elp3 or gcnE, and the number of asexual spores (conidia) in the ΔgcnE mutant was significantly reduced. Moreover, the mRNA levels of the key asexual development regulators were also significantly low in the ΔgcnE mutant compared to wild type (WT). Whereas both the Δelp3 and ΔgcnE mutants were markedly impaired in the formation of adherent biofilms, the ΔgcnE mutant showed a complete loss of surface structure and of intercellular matrix. The ΔgcnE mutant responded differently to oxidative stressors and showed significant susceptibility to triazole antifungal agents. Furthermore, Elp3 and GcnE function oppositely in the production of secondary metabolites, and the ΔgcnE mutant showed attenuated virulence. In conclusion, Elp3 and GcnE are associated with diverse biological processes and can be potential targets for controlling the pathogenic fungus.

Keywords: Aspergillus fumigatus; GNAT family; biofilm formation; histone acetyltransferase; secondary metabolites; stress responses; virulence.

MeSH terms

  • Aspergillus fumigatus* / metabolism
  • Fungal Proteins* / genetics
  • Fungal Proteins* / metabolism
  • Gene Expression Regulation, Fungal
  • Histone Acetyltransferases / genetics
  • Histone Acetyltransferases / metabolism
  • Humans
  • Spores, Fungal
  • Virulence / genetics

Substances

  • Fungal Proteins
  • Histone Acetyltransferases