New strategies for parasite control: Identification of candidate target proteins using the example of thorny-headed worms (Acanthocephala)

棘头虫(棘头虫)是一种全球性的寄生虫，存在于脊椎动物的肠道中，包括人和牲畜。在南美洲的大型养鱼场，这种侵扰达到了如此严重的程度，导致鱼类生长速度减慢、变形和死亡，导致显著的生产力损失。然而，现有的预防措施对环境有害或不切实际。此外，许多驱虫剂(驱虫剂)用于对付棘头虫和其他寄生虫，对各种生物的细胞都有毒性作用。其中一些化疗药物甚至被考虑在癌症治疗中作为细胞抑制剂再次使用。另一个问题是，在动物生产中使用驱虫剂的残留物已经在德国和其他国家的土壤和水域中检测到，在这些国家，它们特别可能损害较小的动物。最后但并非最不重要的一点是，对现有驱虫剂产生抗药性的寄生虫菌株数量正在增加。拟议的项目解决了由此产生的对新治疗策略的高需求：应应用新的生物信息学概念来识别其抑制有望有效杀死寄生虫的蛋白质，同时保护人类、牲畜和环境。由于其对养殖场的破坏性影响以及水产养殖对人类营养的重要性，应建立寄生鱼类棘头虫的候选目标识别程序。该工作流程将包括对基因组和转录体的进化和发育分析，对暴露的寄生虫组织的蛋白质组学分析，以及对有希望的候选目标蛋白质的结构的预测。为了启动高度特异性的寄生虫控制，在棘头虫的进化过程中应该出现一个候选靶标或发生强烈的改变。此外，无论棘头虫在不同寄主类型中的发育水平如何，都将大量生产候选目标。以这种方式确定的候选靶标的抑制有可能干预基本的生命功能，从而有效地杀死棘头虫。候选靶标在暴露的组织中的高表达也应使其能够容易地被活性物质访问，其结构应表明与此类化合物结合的倾向。如果数据库中已经有合适的低分子化合物，将模拟它们与候选目标的相互作用。在该项目完成后，针对候选靶标的药物可以进行调整或(进一步)开发，并测试其对棘头虫的疗效。为了方便将这一概念应用于其他寄生虫，工作流程将通过互联网平台提供。重要的是，该项目提供了对寄生虫的进化和表型可塑性的洞察。

Thorny-headed worms (Acanthocephala) are globally occurring parasites in the intestines of vertebrates, including humans and livestock. In the large fish farms of South America, the infestation reaches such an extent that reduced growth rates, deformations, and death of the fish result in a significant loss of productivity. However, the available preventative measures are environmentally harmful or impracticable. In addition, many deworming agents (anthelmintics), which are used against acanthocephalans and other parasites, have a toxic effect on the cells of a wide range of organisms. Some of these chemotherapeutics are even being considered for second use as cytostatic agents in cancer treatment. Another problem is that residues from the use of anthelmintics in animal production are already detectable in soils and waters of Germany and other countries, where they can damage smaller animals in particular. Last but not least, the number of strains of parasites showing resistance to established anthelmintics is growing. The proposed project addresses the resulting high demand for new treatment strategies: A novel bioinformatic concept shall be applied to identify proteins whose inhibition promises an effective killing of parasites while at the same time sparing humans, livestock and the environment. Due to their damaging effect on fish farms and the great importance of aquacultures for human nutrition, the procedure of candidate target identification shall be established on fish-parasitizing acanthocephalans. The workflow will include evolutionary and developmental analyses of genomes and transcriptomes, proteomic analysis of exposed parasite tissue, and predictions of the structure of promising candidate target proteins. In order to initiate highly specific parasite control, a candidate target should have arisen or been strongly altered in the evolution of Acanthocephala. In addition, a candidate target is to be produced in large quantities regardless of the level of development achieved by the acanthocephalans in different host types. The inhibition of a candidate target defined in this way holds the prospect for intervention in basic vital functions and thus effective killing of acanthocephalans. High expression of a candidate target in exposed tissue should also allow it to be readily accessible to active substances and its structure should indicate a propensity to bind such compounds. If suitable low molecular weight compounds are already available in the databases, their interaction with candidate targets will be simulated. After the project, drugs directed against the candidate targets can be adapted or (further) developed and tested for their efficacy against acanthocephalans. In order to facilitate the application of the concept to other parasites, the workflow is to be made available via an internet platform. Not least, the project offers the perspective to provide insights into the evolution and phenotypic plasticity of parasites.