Quantitative proteomic analyses of Schistosoma japonicum in response to artesunate

Abstract

Artesunate (ART) has high prophylactic efficacy against Schistosoma japonicum infections and has been used to treat and prevent schistosomiasis in China since 1995. However, the molecular mechanism of ART's effects on S. japonicum remains unclear. Herein, we applied isobaric tagging reagents for relative and absolute quantification analyses coupled with two-dimensional liquid chromatography and tandem mass spectrometry to investigate the effect of ART on the proteome of S. japonicum in susceptible mice. 4529 proteins were quantified on the basis of 21 825 unique peptides. Comparative proteomic analyses revealed that 145, 228 and 185 proteins were significantly differentially expressed after ART treatment in schistosomula, juvenile and adult worms, respectively. Ninety proteins were differentially expressed between each two treatment groups in response to ART treatment: 67 proteins were associated with S. japonicum development/aging and 23 were specifically associated with ART treatment. Quantitative real-time PCR of selected genes verified the proteomic data. Gene ontology annotation and Kyoto encyclopedia of genes and genomes pathway mapping analysis showed that the majority of differentially expressed proteins were involved in stress/defense/detoxification, signal transduction, carbohydrate metabolism, amino acid metabolism, transcription/translation, and protein synthesis/assembly/degradation. Thirty-four of the proteins differentially expressed under ART treatment encoded hypothetical, uncharacterized proteins with unknown functions. This study obtained the first comprehensive protein expression profile of S. japonicum in response to ART, and provides a basis for a better understanding of the molecular mechanisms of ART effects on S. japonicum.