Identification of antiparasitic drug targets using a multi-omics workflow in the acanthocephalan model

Abstract

Background With the expansion of animal production, parasitic helminths are gaining increasing economic importance. However, application of several established deworming agents can harm treated hosts and environment due to their low specificity. Furthermore, the number of parasite strains showing resistance is growing, while hardly any new anthelminthics are being developed. Here, we present a bioinformatics workflow designed to reduce the time and cost in the development of new strategies against parasites. The workflow includes quantitative transcriptomics and proteomics, 3D structure modeling, binding site prediction, and virtual ligand screening. Its use is demonstrated for Acanthocephala (thorny-headed worms) which are an emerging pest in fish aquaculture. We included three acanthocephalans (Pomphorhynchus laevis, Neoechinorhynchus agilis, Neoechinorhynchus buttnerae) from four fish species (common barbel, European eel, thinlip mullet, tambaqui). Results The workflow led to eleven highly specific candidate targets in acanthocephalans. The candidate targets showed constant and elevated transcript abundances across definitive and accidental hosts, suggestive of constitutive expression and functional importance. Hence, the impairment of the corresponding proteins should enable specific and effective killing of acanthocephalans. Candidate targets were also highly abundant in the acanthocephalan body wall, through which these gutless parasites take up nutrients. Thus, the candidate targets are likely to be accessible to compounds that are orally administered to fish. Virtual ligand screening led to ten compounds, of which five appeared to be especially promising according to ADMET, GHS, and RO5 criteria: tadalafil, pranazepide, piketoprofen, heliomycin, and the nematicide derquantel. Conclusions The combination of genomics, transcriptomics, and proteomics led to a broadly applicable procedure for the cost- and time-saving identification of candidate target proteins in parasites. The ligands predicted to bind can now be further evaluated for their suitability in the control of acanthocephalans. The workflow has been deposited at the Galaxy workflow server under the URL tinyurl.com/yx72rda7.

Substantial hierarchical reductions of genetic and morphological traits in the evolution of rotiferan parasites

“…gDNA reads and nuclear draft genome of N. agilis can be retrieved from Genbank under BioProject accession PRJNA1126620 and BioSample accession SAMN41948513. Details on generation and key features of the draft genome are given elsewhere (Supplementary Note S2 of (Schmidt et al 2022))…”

Hooking the scientific community on thorny-headed worms: interesting and exciting facts, knowledge gaps and perspectives for research directions on Acanthocephala

“…The first whole genome of an acanthocephalan, Pomphorhynchus laevis, was generated by Mauer et al (2020) [105] and was recently used to explore the phylogenomic relationships within Rotifera-Acanthocephala [106]. Draft genomes of additional species of acanthocephalans are currently being assembled [150]. High throughput phylogenomics based on Expressed Sequence Tags (EST) data [182], target enrichment of "ultraconserved elements" (UCEs) and/or Anchored Hybrid Enrichment (AHE) to design a large probe set of hundreds of loci could be implemented in the future (see Karin et al [85] for a review of these phylogenomics methods).…”