Transcriptional responses ofBiomphalaria pfeifferiandSchistosoma mansonifollowing exposure to niclosamide, with evidence for a synergistic effect on snails following exposure to both stressors

abstractBackgroundSchistosomiasis is one of the world’s most common NTDs. Successful control operations often target snail vectors with the molluscicide niclosamide. Little is known about how niclosamide affects snails, including forBiomphalaria pfeifferi, the most important vector forSchistosoma mansoniin Africa. We used Illumina technology to explore how field-derivedB. pfeifferi, either uninfected or harboring cercariae–producingS. mansonisporocysts, respond to a sublethal exposure of niclosamide. This study afforded the opportunity to determine if snails respond differently to biotic or abiotic stressors, and if they reserve unique responses for when presented with both stressors in combination. We also examined how sporocysts respond when their snail host is exposed to niclosamide.Principal FindingsCercariae-producing sporocysts within snails exposed to niclosamide express ~68% of the genes in theS. mansonigenome, as compared to 66% expressed by intramolluscan stages ofS. mansoniin snails not exposed to niclosamide. Niclosamide does not disable sporocysts nor does it seem to provoke from them distinctive responses associated with detoxifying a xenobiotic. ForB. pfeifferi, niclosamide treatment alone increases expression of several features not up-regulated in infected snails including particular cytochrome p450s and heat shock proteins, glutathione-S-transferases, antimicrobial factors like LBP/BPI and protease inhibitors, and also provokes strong down regulation of proteases. Exposure of infected snails to niclosamide resulted in numerous up-regulated responses associated with apoptosis along with down-regulated ribosomal and defense functions, indicative of a distinctive, compromised state not achieved with either stimulus alone.Conclusions/SignificanceThis study helps define the transcriptomic responses of an important and under-studied schistosome vector toS. mansonisporocysts, to niclosamide, and to both in combination. It suggests the response ofS. mansonisporocysts to niclosamide is minimal and not reflective of a distinct repertoire of genes to handle xenobiotics while in the snail host. It also offers new insights for how niclosamide affects snails.Author’S SummarySchistosomaisis control programs often employ the use of chemical molluscicides, such as niclosamide, to control the obligatory intermediate snail hosts. Despite its widespread use, we know little about how niclosamide affects snails likeBiomphalaria pfeifferi, the most important vectorSchistosoma mansoniin Africa. By sequencing the transcriptomes of uninfected andS. mansoni-infectedB. pfeifferiexposed to niclosamide, we analyze the snail’s response to both biotic and abiotic stressors. We can also examine the response ofS. mansonito niclosamide exposure during intramolluscan development.Biomphalaria pfeifferisnails exposed only to niclosamide showed unique up-regulation of stress and defense-related transcripts not seen in snails infected with a biotic, likeS. mansoniinfection, alone.Schistosoma mansoni-infectedB. pfeifferiexposed to niclosamide were clearly unable to regulate normal metabolic and detoxification processes. Cercariae-producing sporocysts within snails exposed to niclosamide are largely unaffected and continue to produce transcripts required for cercariae production.