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Tissue-specific and sex-biased glycoproteomic landscape of Schistosoma mansoni

ABSTRACT: Schistosomiasis is a major global public health challenge. Protein glycosylation plays a crucial role in cellular activities and pathogen-host immune interactions, yet its global features and functions in schistosomes have not been thoroughly explored. Here, we employed pGlyco3 and pGlycoNovo to identify glycoproteins and glycopeptides. Quantitative analysis using pGlycoQuant enabled the construction of a large-scale intact N- and O-glycoproteomic library for S. mansoni.The dataset includes: N-glycoproteomics data of adult Schistosoma mansoni females (20231124-CX-Cpg), N-glycoproteomics data of adult males (20231124-CX-Xpg), O-glycoproteomics data of adult females (20240403-CX-C), and O-glycoproteomics data of adult males (20240403-CX-X). The latest identification and quantification output files are in the /update/2025-12-01 folder.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Schistosoma Mansoni (ncbitaxon:6183)

SUBMITTER: Xu Chen

PROVIDER: MSV000097695 | MassIVE | Wed Apr 23 01:35:00 BST 2025

SECONDARY ACCESSION(S): PXD063230

REPOSITORIES: MassIVE

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Project description:Background: Treatment and morbidity control of schistosomiasis relies on a single drug, praziquantel. Therefore, there is a pressing need to explore the effects of PZQ on the parasites at the molecular level and to pursue alternative and/or or synergistic drugs against schistosomiasis. Methodology: We used a custom-designed Schistosoma mansoni oligo-microarray to explore the effects of a sublethal dose of praziquantel on S. mansoni adult worms’ gene expression. We used functional analysis of gene interaction networks to identify differentially expressed genes that are known targets of other drugs already tested in humans for diverse disease conditions. Omeprazole, a proton pump inhibitor drug that is widely prescribed, was tested in combination with praziquantel. We comparatively assessed the efficacy of praziquantel or omeprazole alone and in combination against S. mansoni adult worms in vitro over a period of 120 hours. Principal Findings: We identified sets of genes that were affected by praziquantel on both paired and unpaired females, however with opposite gene expression patterns (up-regulated in paired and down-regulated in unpaired females), indicating that the transcriptomics changes induced by praziquantel are heavily influenced by the mating status. We also identified genes that were similarly affected by praziquantel in males and females. The use of sublethal doses of praziquantel together with omeprazole showed a significantly enhanced worm mortality in vitro compared to praziquantel alone, thus evidencing a synergic effect. Conclusions: Functional analysis of gene interaction networks is an important approach to identify genes whose expression is affected by one drug and that are at the same time known targets of other drugs already tested in humans for diverse disease conditions, thus pointing the latter as possible synergic drugs. Combined treatment with omeprazol increases the efficacy of praziquantel against S. mansoni adult worms in vitro, and additional in vivo studies are warranted.

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Tissue-specific and sex-biased glycoproteomic landscape of Schistosoma mansoni

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