New strategies for parasite control: Identification of candidate target proteins using the example of thorny-headed worms (Acanthocephala)
Bioinformatics and Theoretical Biology
Developmental Biology
Evolution, Anthropology
Parasitology and Biology of Tropical Infectious Disease Pathogens
Structural Biology
Final Report Abstract
Parasites are a major public health issue in many countries and reduce productivity in husbandry worldwide. However, the administration of many drugs against parasites is problematic because they harm a wide range of organisms, including the treated individuals. The problem is particularly evident in the example of the fish farms in the Amazon basin. Here, the infestation of fish with intestinal parasites from the group of thornyheaded worms (Acanthocephala) causes high losses in productivity. Dissipation of large amounts of established deworming agents and their metabolites from the hectare-sized fish ponds would foreseeably have a negative impact on natural life communities in adjacent water bodies. In fact, there is still a lack of effective and targeted (specific) and, hence, welltolerable and sustainable thorny-headed worm control. Following on from this, the project aimed to devise new strategies for the development of effective and specific parasite control using the example of fish-parasitizing thorny-headed worms. First, we generated large sequence datasets of several key species, thereunder acanthocephalans. For each of these species, we reconstructed the nuclear genome (genetic make-up) and all transcripts (entirety of read gene information). From the latter, we derived all proteins, which were also quantitatively analyzed by mass spectrometry. The analyses led to the identification of eleven acanthocephalan proteins that should be good starting points for effective parasite control. Most of these candidate targets additionally promise high specificity: The transcripts were found in all fish-parasitizing thorny-headed worms studied. However, no corresponding proteins were identified in other species. The same proteins are likely to be very important for the survival of the worms. This is because their transcripts occurred in thorny-headed worms of different sexes and variant maturation stages in largely constant and high amounts. The proteins focused were further highly abundant in the body wall of thorny-headed worms. Thus, they should be easily accessible for drugs orally administered to the fish, e.g. with the food. According to our calculations, pharmacologically active substances dock onto the selected proteins. The actual suitability of these substances as new deworming agents can now be tested in living thorny-headed worms. The workflow of bioinformatics applications for candidate target identification is accessible via the internet and can be applied to other parasites. The new datasets are accessible via public databases. Own follow-up analyses revealed that thorny-headed worms have mechanisms for the maintenance of genome integrity (piRNA pathway). Moreover, numbers of protein-coding genes and molecules, which influence protein amounts (microRNAs), are greatly reduced. Further studies shed light on the phylogeny and the various reproductive modes of acanthocephalans and their closer relatives.
Publications
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Genomics and transcriptomics of epizoic Seisonidea (Rotifera, syn. Syndermata) reveal strain formation and gradual gene loss with growing ties to the host. BMC Genomics, 22(1).
Mauer, Katharina M.; Schmidt, Hanno; Dittrich, Marco; Fröbius, Andreas C.; Hellmann, Sören Lukas; Zischler, Hans; Hankeln, Thomas & Herlyn, Holger
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Host-dependent impairment of parasite development and reproduction in the acanthocephalan model. Cell & Bioscience, 12(1).
Schmidt, Hanno; Mauer, Katharina; Hankeln, Thomas & Herlyn, Holger
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Identification of antiparasitic drug targets using a multi-omics workflow in the acanthocephalan model. BMC Genomics, 23(1).
Schmidt, Hanno; Mauer, Katharina; Glaser, Manuel; Dezfuli, Bahram Sayyaf; Hellmann, Sören Lukas; Silva, Gomes Ana Lúcia; Butter, Falk; Wade, Rebecca C.; Hankeln, Thomas & Herlyn, Holger
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Nuclear genome annotation of wheel animals and thorny-headed worms: inferences about the last common ancestor of Syndermata (Rotifera s.l.). Hydrobiologia, 851(12-13), 2827-2844.
Hagemann, Laura; Mauer, Katharina M.; Hankeln, Thomas; Schmidt, Hanno & Herlyn, Holger
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Whole-genome analyses converge to support the Hemirotifera hypothesis within Syndermata (Gnathifera). Hydrobiologia, 851(12-13), 2795-2826.
Vasilikopoulos, Alexandros; Herlyn, Holger; Fontaneto, Diego; Wilson, Christopher Gordon; Nowell, Reuben William; Flot, Jean-François; Barraclough, Timothy Giles & Van, Doninck Karine
