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Abstract
Toxoplasma gondii is a leading cause of neurological birth defects and a serious opportunistic pathogen. The authors and others have found that Toxoplasma uses a unique nucleosome composition supporting a fine gene regulation together with other factors. Post-translational modifications in histones facilitate the establishment of a global chromatin environment and orchestrate DNA-related biological processes. Histone acetylation is one of the most prominent post-translational modifications influencing gene expression. Histone acetyltransferases and histone deacetylases have been intensively studied as potential drug targets. In particular, histone deacetylase 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 histone acetyltransferases and histone deacetylases, and discuss the inhibitors studied to date. Finally, the authors discuss the distinct possibility that the unique nucleosome composition of Toxoplasma, which harbors a nonconserved H2Bv variant histone, might be targeted in novel therapeutics directed against this parasite.
Acknowledgements
We thank Maria Lis Alomar and Andres Alonso for their help with the figures.
Financial & competing interests disclosure
SO Angel (Researcher), MC Dalmasso, SS Bogado and L Vanagas (Fellows) are members of National Research Council of Argentina (CONICET). SO Angel and L Vanagas are also professors of UNSAM. This work was supported by NIH-NIAID 1R01AI083162 (to SO Angel and WJ Sullivan) and NIH R01 AI077502 (to WJ Sullivan). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.