The histone acetyltransferase GcnE regulates conidiation and biofilm formation in Aspergillus fumigatus
Journal
Medical Mycology
Date Issued
2019
Author(s)
Abstract
Histone modifications play a crucial role in eukaryotic gene regulation. The Spt-Ada-Gcn5-acetyltransferase (SAGA) complex controls histone acetylation, with Gcn5 (GcnE) acting as the acetyltransferase. In the Aspergillus species, GcnE has been shown to regulate asexual development and secondary metabolism. Apart from this, GcnE is required for pathogenicity in plant fungal pathogen A. flavus; however, the role of GcnE in the pathogenicity of human pathogenic fungus A. fumigatus is unknown. In this study, we uncovered the key roles of GcnE in A. fumigatus conidiation, stress responses, and biofilm formation. We observed that deletion of gcnE resulted in aberrant conidiation in which conidiophores displayed abnormal phialide formation. In addition, the ΔgcnE mutant grew slightly faster under limited nitrogen sources (1 mM of ammonium or nitrate) compared to the wild type. The ΔgcnE mutant exhibited increased susceptibility to cell wall-perturbing agents, H2O2 and menadione but enhanced tolerance to LiCl. Furthermore, we showed that GcnE is involved in biofilm formation, and overexpression of adherence-related genes such as somA or uge3 partially rescued biofilm formation defects in the ΔgcnE mutant background. Interestingly, GcnE was not required for virulence in a neutropenic murine model of invasive aspergillosis. These results suggest that GcnE is critical for conidiation and biofilm formation but not virulence in A. fumigatus. ? 2019 The Author(s) 2019. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.
Subjects
A. fumigatus; biofilm formation; conidiation; GcnE; virulence
Other Subjects
ammonia; histone acetyltransferase; histone acetyltransferase gcne; hydrogen peroxide; lithium chloride; menadione; nitrate; nitrogen; nucleic acid; unclassified drug; fungal protein; histone acetyltransferase; animal experiment; animal model; Article; Aspergillus fumigatus; biofilm; cell wall; controlled study; fungal virulence; fungus growth; invasive aspergillosis; nitrogen utilization; nonhuman; oxidative stress; stress; vegetative growth; animal; Aspergillus fumigatus; biofilm; enzymology; female; fungus spore; gene deletion; gene expression regulation; genetics; growth, development and aging; Institute for Cancer Research mouse; metabolism; microbiology; mouse; mutation; systemic mycosis; virulence; Animals; Aspergillus fumigatus; Biofilms; Female; Fungal Proteins; Gene Deletion; Gene Expression Regulation, Fungal; Histone Acetyltransferases; Invasive Fungal Infections; Mice; Mice, Inbred ICR; Mutation; Nitrogen; Spores, Fungal; Virulence
Type
journal article