The Role of NAD+-dependent lysine deacetylases (Sirtuin) and their Inhibitors in Aspergillus fumigatus acetylome and virulence

ABSTRACT: Protein acetylation is a posttranslational modification that orchestrates gene regulation and various biological processes, such as fungal pathogenesis. One promising strategy for treating fungal infections is targeting the enzymes that regulate protein acetylation. Sirtuins, an NAD+-dependent lysine deacetylase, have been described as histone deacetylase and as regulators of secondary metabolism in various Aspergillus spp. However, the roles of sirtuin remain unclear. We employed a comprehensive set of experimental techniques, including gene deletion, phenotyping, in vivo virulence assays, metabolome analysis, transcriptome analysis, and acetylome analysis. Our findings reveal that sirtuins in A. fumigatus are intricately involved in crucial cellular processes such as cell wall integrity, secondary metabolite (SM) production, protease secretion, thermotolerance, and virulence. Notably, among the six sirtuins studied, AFSirE exerts a major influence on the phenotype of A. fumigatus. Furthermore, through acetylome analysis, we identified 42 and 260 proteins exhibiting differential acetylation in the AfSirE and SIRTko strains, respectively. Transcriptome data obtained from RNA sequencing (RNA-seq) demonstrated that sirtuins play a regulatory role in the expression of genes associated with SM production, cell wall component biosynthesis, and a variety of virulence factors.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Neosartorya Fumigata (aspergillus Fumigatus)

SUBMITTER: Adriana Franco Paes Leme  

LAB HEAD: Adriana Franco Paes Leme

PROVIDER: PXD044964 | Pride | 2024-06-20

REPOSITORIES: Pride