Cestode parasites cause neglected diseases, such as echinococcosis and cysticercosis, which represent a significant problem in human and animal health. Benzimidazoles and praziquantel are the only available drugs for chemotherapy and it is therefore important to identify new alternative drugs against cestode parasites. Histone deacetylases (HDACs) are validated drug targets for the treatment of cancer and other diseases, including neglected diseases. However, knowledge of HDACs in cestodes is very scarce. In this work, we investigated cestode HDACs as potential drug targets to develop new therapies against neglected diseases caused by cestodes. Here we showed the full repertoire of HDAC coding genes in several members of the class Cestoda. Between 6 and 7 zinc-dependent HDAC coding genes were identified in the genomes of species from Echinococcus, Taenia, Mesocestoides and Hymenolepis genera. We classified them as Class I and II HDACs and analyzed their transcriptional expression levels throughout developmental stages of Echinococcus spp. We confirmed for the first time the complete HDAC8 nucleotide sequences from Echinococcus canadensis G7 and Mesocestoides corti. Homology models for these proteins showed particular structural features which differentiate them from HDAC8 from Homo sapiens. Furthermore, we showed that Trichostatin A (TSA), a pan-HDAC inhibitor, decreases the viability of M. corti, alters its tegument and morphology and produces an increment of the total amount of acetylated proteins, including acetylated histone H4. These results suggest that HDAC from cestodes are functional and might play important roles on survival and development. The particular structural features observed in cestode HDAC8 proteins suggest that these enzymes could be selectively targeted. This report provides the basis for further studies on cestode HDAC enzymes and for discovery of new HDAC inhibitors for the treatment of neglected diseases caused by cestode parasites.

中文翻译：

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组蛋白脱乙酰酶作为绦虫引起的被忽视的热带病的潜在药物靶点。

绦虫寄生虫引起被忽视的疾病，例如包虫病和囊尾蚴病，这是人类和动物健康的一个重大问题。苯并咪唑和吡喹酮是唯一可用的化疗药物，因此寻找针对绦虫寄生虫的新替代药物非常重要。组蛋白脱乙酰酶 (HDAC) 是治疗癌症和其他疾病（包括被忽视的疾病）的经过验证的药物靶点。然而，关于绦虫中 HDAC 的知识却非常匮乏。在这项工作中，我们研究了绦虫 HDAC 作为潜在的药物靶点，以开发针对绦虫引起的被忽视疾病的新疗法。在这里，我们展示了绦虫纲的几个成员中 HDAC 编码基因的完整库。在棘球绦虫属、带绦虫属、中绦虫属和膜壳皮属物种的基因组中鉴定出 6 至 7 个锌依赖性 HDAC 编码基因。我们将它们分类为 I 类和 II 类 HDAC，并分析了它们在棘球绦虫属整个发育阶段的转录表达水平。我们首次确认了来自加拿大棘球绦虫G7和Mesocestoides corti的完整HDAC8核苷酸序列。这些蛋白质的同源模型显示出特殊的结构特征，将它们与智人的 HDAC8 区分开来。此外，我们还发现，曲古抑菌素 A (TSA) 是一种泛 HDAC 抑制剂，可降低 M. corti 的活力，改变其外皮和形态，并产生乙酰化蛋白总量的增加，包括乙酰化组蛋白 H4。这些结果表明绦虫中的 HDAC 具有功能性，可能对生存和发育发挥重要作用。在绦虫 HDAC8 蛋白中观察到的特殊结构特征表明这些酶可以被选择性地靶向。该报告为绦虫HDAC酶的进一步研究和发现新的HDAC抑制剂用于治疗绦虫寄生虫引起的被忽视的疾病提供了基础。