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.

中文翻译：

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原生动物寄生虫中的Bromodomains：进化，功能和药物开发的机会。

寄生虫感染仍然是当今全球最紧迫的健康问题，影响数十亿人，并造成不可持续的经济负担。耐药性寄生虫的兴起已迫切需要研究其生物学，以期发现新的潜在药物靶标。已经确定，通过干扰赖氨酸乙酰化而破坏基因表达对apicomplexan（弓形虫和疟原虫）和动囊体（利什曼原虫和Trypanosoma spp。）寄生虫的存活是有害的。作为赖氨酸乙酰化的“阅读器”，溴结构域蛋白已成为关键的基因表达调节剂和有希望的新型药物靶标。在这里，我们回顾了最近的研究，这些研究证明了含溴结构域的蛋白质在寄生虫生存力，侵袭，以及阶段切换和当前工作表明了溴结构域抑制剂作为新型抗寄生虫药的功效。此外，我们对代表性病原体中的溴结构域蛋白进行了系统发育分析，其中一些具有独特的功能，可能对寄生虫过程具有特异性，并在未来的药物开发中有用。