Contributions of a Histone Deacetylase (SirT2/Hst2) to Beauveria bassiana Growth, Development, and Virulence.

Qing Cai,Jia-Tao Xie,Li Tian,Nemat O Keyhani,Dao-Hong Jiang

doi:10.3390/jof8030236

Abstract

Sirtuins are a class of histone deacetylases that promote heterochromatin formation to repress transcription. The entomopathogenic fungus Beauveria bassiana contains six sirtuin homologs. The class III histone deacetylase, BbSir2, has been previously shown to affect the regulation of carbon/nitrogen metabolism and asexual development, with only moderate effects on virulence. Here, we examine another class III histone deacetylase (BbSirT2) and show that it contributes to deacetylation of lysine residues on histone H4-K16ac. Directed gene-knockout of BbSirT2 dramatically reduced conidiation, the ability of the fungus to metabolize a range of carbon and nitrogen sources, and tolerances to oxidative, heat, and UV stress and significantly attenuated virulence in both intrahemocoel injection and topical bioassays using the Greater wax moth (Galleria mellonella) as the insect host. ΔBbSirT2 cells showed alterations in cell cycle development and hyphal septation and produced morphologically aberrant conidia. Comparative transcriptomic analyses of wild type versus ΔBbSirT2 cells indicated differential expression of 1148 genes. Differentially expressed genes were enriched in pathways involved in cell cycle and rescue, carbon/nitrogen metabolism, and pathogenesis. These included changes in the expression of polyketide synthases (PKSs) and LysM effector proteins that contribute to degradation of host toxins and target host pathways, respectively. These data indicate contributions of BbSirT2 in helping to mediate fungal stress and development, with the identification of affected gene targets that can help account for the observed reduced virulence phenotype.

Highlights

Histone acetylation and deacetylation are post-translational protein modifications that impact core molecular processes of gene expression by mediating transitions between transcriptionally repressed and active chromatin states [1–3]
Histone deacetylation is mediated by histone deacetylases (HDACs), a multifamily enzyme family found in all eukaryotes, capable of catalyzing the deacetylation of lysine residues (Kac sites) on histones and other proteins [4–6]
Amino acid lysine (K) acetylation catalyzed by HDACs can occur on non-histone targets, directly affecting cell processes ranging from transcription to signaling and response pathways and protein synthesis, affecting cell cycle progression, metabolism, stress and immune responses, and, in the case of pathogens, virulence [3,8]

Summary

Introduction

Histone acetylation and deacetylation are post-translational protein modifications that impact core molecular processes of gene expression by mediating transitions between transcriptionally repressed and active chromatin states [1–3]. Histone deacetylation is mediated by histone deacetylases (HDACs), a multifamily enzyme family found in all eukaryotes, capable of catalyzing the deacetylation of lysine residues (Kac sites) on histones and other proteins [4–6]. Different subfamilies of histone deacetylases (HDACs) have been characterized, including class I and class II enzyme families, e.g., the Rpd3/Hda1-like. Amino acid lysine (K) acetylation catalyzed by HDACs can occur on non-histone targets, directly affecting cell processes ranging from transcription to signaling and response pathways and protein synthesis, affecting cell cycle progression, metabolism, stress and immune responses, and, in the case of pathogens, virulence [3,8]. In addition to catalyzing the protein deacetylation reaction, sirtuins can mediate the removal of succinyl, malonyl, myristoyl, and/or palmitoyl groups from amino acid side chains [9–11].

Methods

Results

Discussion

Conclusion