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

• Applicant: Professor Dr. Holger Herlyn
• Subject Area: Veterinary Medical Science ; Bioinformatics and Theoretical Biology ; Developmental Biology ; Evolution, Anthropology ; Parasitology and Biology of Tropical Infectious Disease Pathogens ; Structural Biology
• Term: from 2020 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 435334615

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.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Thomas Hankeln