Bromodomains in protozoan parasites: Evolution, function, and opportunities for drug development

Victoria Jeffers, Chunlin Yang, Sherri Huang, William J. Sullivan

Research output: Contribution to journalReview articlepeer-review

16 Scopus citations

Abstract

Parasitic infections remain one of the most pressing global health concerns of our day, affecting billions of people and producing unsustainable economic burdens. The rise of drug-resistant parasites has created an urgent need to study their biology in hopes of uncovering new potential drug targets. It has been established that disrupting gene expression by interfering with lysine acetylation is detrimental to survival of apicomplexan (Toxoplasma gondii and Plasmodium spp.) and kinetoplastid (Leishmania spp. and Trypanosoma spp.) parasites. As "readers" of lysine acetylation, bromodomain proteins have emerged as key gene expression regulators and a promising new class of drug target. Here we review recent studies that demonstrate the essential roles played by bromodomain-containing proteins in parasite viability, invasion, and stage switching and present work showing the efficacy of bromodomain inhibitors as novel antiparasitic agents. In addition, we performed a phylogenetic analysis of bromodomain proteins in representative pathogens, some of which possess unique features that may be specific to parasite processes and useful in future drug development.

Original languageEnglish (US)
Article numbere00047-16
JournalMicrobiology and Molecular Biology Reviews
Volume81
Issue number1
DOIs
StatePublished - Mar 2017

Keywords

  • Epigenetics
  • Leishmania
  • Malaria
  • Plasmodium
  • Toxoplasma
  • Trypanosomes

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology
  • Infectious Diseases

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