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Transcriptional Responses of Schistosoma japonicum Exposed in vivo to Sub-Lethal Dosages of Praziquantel

ABSTRACT: We have used a Schistosoma japonicum infected murine model with in vivo sub-lethal dosages of praziquantel against adult parasites. Differential gene expression of parasites was followed between 30 minutes and 24 hours post- drug administration, using a whole transcriptome microarray platform. Differential gene expression was considered separately between parasite gender.

ORGANISM(S): Schistosoma japonicum

PROVIDER: GSE41149 | GEO | 2012/09/27

SECONDARY ACCESSION(S): PRJNA175998

REPOSITORIES: GEO

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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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Transcriptional Responses of Schistosoma japonicum Exposed in vivo to Sub-Lethal Dosages of Praziquantel

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