Toxoplasma histone acetylation remodelers as novel drug targets

Abstract

Toxoplasma gondii is a leading cause of neurological birth defects and a serious opportunistic pathogen. We and others have found that Toxoplasma uses a unique nucleosome composition supporting a fine gene regulation together with other factors. Post-translational modifications (PTMs) on histones facilitate the establishment of a global chromatin environment and orchestrate DNA-related biological processes. Histone acetylation is one of the most prominent PTMs, influencing gene expression. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) have been intensively studied as potential drug targets. In particular, HDAC inhibitors have activity against Apicomplexan parasites, underscoring their potential as a new class of antiparasitic compounds. In this review, we summarize what is known about Toxoplasma HATs and HDACs, and discuss the inhibitors studied to date. Finally, we discuss the distinct possibility that the unique nucleosome composition of Toxoplasma, which harbors a non-conserved H2Bv variant histone, might be targeted in novel therapeutics directed against this parasite.