Suppression of mRNAs encoding tegument tetraspanins from Schistosoma mansoni results in impaired tegument turnover

Schistosomes express a family of integral membrane proteins,called tetraspanins (tsps),in the outer surface membranes of the tegument. two of these tetraspanins,sm-tsp-1 and sm-tsp-2,confer protection as vaccines in mice,and individuals who are naturally resistant to s. mansoni infection mount a strong igg response to sm-tsp-2. to determine their functions in the tegument of s. mansoni we used rna interference to silence expression of sm-tsp-1 and sm-tsp-2 mrnas. soaking of parasites in sm-tsp dsrnas resulted in 61% (p = 0.009) and 74% (p = 0.009) reductions in sm-tsp-1 and sm-tsp-2 transcription levels,respectively,in adult worms,and 67%-75% (p = 0.011) and 69%-89% (p = 0.004) reductions in sm-tsp-1 and sm-tsp-2 transcription levels,respectively,in schistosomula compared to worms treated with irrelevant control (luciferase) dsrna. ultrastructural morphology of adult worms treated in vitro with sm-tsp-2 dsrna displayed a distinctly vacuolated and thinner tegument compared with controls. schistosomula exposed in vitro to sm-tsp-2 dsrna had a significantly thinner and more vacuolated tegument,and morphology consistent with a failure of tegumentary invaginations to close. injection of mice with schistosomula that had been electroporated with sm-tsp-1 and sm-tsp-2 dsrnas resulted in 61% (p = 0.005) and 83% (p = 0.002) reductions in the numbers of parasites recovered from the mesenteries four weeks later when compared to dsrna-treated controls. these results imply that tetraspanins play important structural roles impacting tegument development,maturation or stability. © 2010 tran et al.