Toxoplasma histone acetylation remodelers as novel drug targets

Laura Vanagas, Victoria Jeffers, Silvina S. Bogado, Maria C. Dalmasso, William J. Sullivan, Sergio O. Angel

Research output: Contribution to journalReview article

18 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1189-1201
Number of pages13
JournalExpert Review of Anti-Infective Therapy
Volume10
Issue number10
DOIs
StatePublished - Oct 1 2012

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Keywords

  • acetylation
  • HATs
  • HDACi
  • HDACs
  • histone
  • therapy
  • Toxoplasma gondii

ASJC Scopus subject areas

  • Infectious Diseases
  • Microbiology (medical)
  • Microbiology
  • Virology

Cite this

Vanagas, L., Jeffers, V., Bogado, S. S., Dalmasso, M. C., Sullivan, W. J., & Angel, S. O. (2012). Toxoplasma histone acetylation remodelers as novel drug targets. Expert Review of Anti-Infective Therapy, 10(10), 1189-1201. https://doi.org/10.1586/eri.12.100