title: Bromodomains in Protozoan Parasites: Evolution, Function, and Opportunities for Drug Development.
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.
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Victoria
authors.identifier: 0000-0003-1233-1088
authors.initials: V
authors.lastname: Jeffers
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Sherri
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, USA wjsulliv@iu.edu.|Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Sullivan
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D044127:Epigenesis, Genetic / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics*; D008239:Lysine / Q000737:chemistry*; D010963:Plasmodium falciparum / Q000378:metabolism*; D000072417:Protein Domains / Q000235:genetics; D011499:Protein Processing, Post-Translational; D015800:Protozoan Proteins / Q000235:genetics; D014122:Toxoplasma / Q000378:metabolism*; D014346:Trypanosoma brucei brucei / Q000378:metabolism*; D014349:Trypanosoma cruzi / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins; D008239:Lysine
keywords: Leishmania; Plasmodium; Toxoplasma; epigenetics; malaria; trypanosomes