Transcriptional analysis of Schistosoma mansoni treated with praziquantel in vitro

Schistosomiasis is one of the foremost health problems in developing countries and has been estimated to account for the loss of up to 56 million annual disability-adjusted life years. Control of the disease relies almost exclusively on praziquantel (PZQ) but this drug does not kill juvenile worms during the early stages of infection or prevent post-treatment reinfection. As the use of PZQ continues to grow, there are fears that drug resistance may become problematic thus there is a need to develop a new generation of more broadly effective anti-schistosomal drugs, a task that will be made easier by having an understanding of why PZQ kills sexually mature worms but fails to kill juveniles. Here, we describe the exposure of mixed-sex juvenile and sexually mature male and female Schistosoma mansoni to 1 μg/mL PZQ in vitro and the use of microarrays to observe changes to the transcriptome associated with drug treatment. Although there was no significant difference in the total number of genes expressed by adult and juvenile schistosomes after treatment, juveniles differentially regulated a greater proportion of their genes. These included genes encoding multiple drug transporter as well as calcium regulatory, stress and apoptosis-related proteins. We propose that it is the greater transcriptomic flexibility of juvenile schistosomes that allows them to respond to and survive exposure to PZQ in vivo.

Treatment of Schistosoma mansoni with the drug praziquantel results in a prolonged muscular contraction and paralysis of the parasite. The molecular processes underlying this effect are investigated using microarrays.Figure optionsDownload high-quality image (129 K)Download as PowerPoint slideHighlights
► The effect of praziquantel on the transcriptome of Schistosoma mansoni is assessed.
► Juvenile worms are able to make a robust transcriptomic response to praziquantel.
► Adult male worms have a relatively weak transcriptomal response to praziquantel.
► Juveniles express genes whose products may protect them from the praziquantel.
► Adult schistosomes may be drug sensitive due to transcriptomal inflexibility.