Project description:Schistosomiasis is an infectious disease infecting mammals as the definitive host and fresh water snails as the intermediate host. Understanding the molecular and biochemical relationship between the causative schistosome parasite and its hosts will be key to understanding and ultimately treating and/or eradicating the disease. There is increasing evidence that pathogens that have co-evolved with their hosts can manipulate their hosts' behaviour at various levels to augment an infection. Bacteria, for example, can induce beneficial chromatin remodelling of the host genome. We have previously shown in vitro that Biomphalaria glabrata embryonic cells co-cultured with schistosome miracidia display genes changing their nuclear location and becoming up-regulated. This also happens in vivo in live intact snails, where early exposure to miracidia also elicits non-random repositioning of genes. We reveal differences in the nuclear repositioning between the response of parasite susceptible snails as compared to resistant snails and with normal or live, attenuated parasites. Interestingly, the stress response gene heat shock protein (Hsp) 70 is only repositioned and then up-regulated in susceptible snails with the normal parasite. This movement and change in gene expression seems to be controlled by the parasite. Other differences in the behaviour of genes support the view that some genes are responding to tissue damage, for example the ferritin genes move and are up-regulated whether the snails are either susceptible or resistant and upon exposure to either normal or attenuated parasite. This is the first time host genome reorganisation has been seen in a parasitic host and only the second time for any pathogen. We believe that the parasite elicits a spatio-epigenetic reorganisation of the host genome to induce favourable gene expression for itself and this might represent a fundamental mechanism present in the human host infected with schistosome cercariae as well as in other host-pathogen relationships.

Project description:Resistance or susceptibility of the snail host Biomphalaria glabrata to Schistosoma mansoni is determined by the genetics of both the snail and parasite. Although Mendelian genetics governs adult resistance to infection, juvenile resistance and susceptibility are complex traits. In this study, suppression subtractive hybridization was used to construct forward and reverse cDNA libraries to identify genes involved in the immediate response of juvenile resistant (BS-90), non-susceptible (LAC2) snails, and susceptible (NMRI) snails after early exposure to S. mansoni. Expressed Sequence Tags (ESTs) were generated from the repertoire of enriched transcripts. In resistant snails, several ESTs corresponded to transcripts involved in immune regulation/defense response. While no defense related transcripts were found among juvenile susceptible snail ESTs, we detected transcripts involved in negative regulation of biological process/morphogenesis/proliferation. Differential gene expression and temporal regulation of representative transcripts were compared among snails pre- and post-exposure to either normal or attenuated miracidia using quantitative real time RT-PCR. Results showed that several transcripts, such as fibrinolytic C terminal domain, cytidine deaminase, macrophage expressed gene 1, protein kinase C receptor, anti-microbial peptide; theromacin and Fas remained up-regulated regardless of whether or not snails were exposed to normal or attenuated miracidia. While ESTs related to C-type lectin and low-density lipoprotein receptor were induced only by exposure to normal miracidia. By comparing changes in gene expression between resistant and susceptible juvenile snails responding either to normal or attenuated parasites, we can conclude that the transcription of genes associated with the intra-dermal penetration process of the snail host by invading miracidia may need to be taken into account when assessing differential gene expression between resistant and susceptible strains of B.glabrata in relation to S. mansoni exposure.

Project description:Snails are essential for the transmission and maintenance of schistosomiasis in endemic areas, as they serve as intermediate hosts for schistosome parasites. A clear understanding of the snail species present, their local distribution and infection status is therefore a prerequisite for effective control of schistosomiasis. The purpose of this study was to establish the infection status and distribution of Schistosoma mansoni in snails in the Gombe area along the shores of Lake Tanganyika in western Tanzania, using both detection of cercarial shedding and molecular approaches.Snails were collected from streams located close to human settlements in Gombe National Park, as well as from nearby villages (Kiziba, Mtanga, Mwamgongo and Bugamba) and the largest town in the region (Kigoma). Snails were individually exposed to light to induce shedding of schistosome larvae, which were examined using a compound light microscope. Additionally, the internal transcribed spacer (ITS) region of the ribosomal RNA gene cluster was simultaneously amplified in both snails and their trematodes using a single polymerase chain reaction (PCR) and sequenced to confirm species identification.Snails morphologically identified as Biomphalaria pfeifferi were present in all streams except at Mtanga but their distribution was patchy in both time and space. Sequencing of PCR products indicated that not all snails were B. pfeifferi. None of the snails from Gombe or Bugamba shed schistosome larvae, while larvae were shed at all other sites. Overall, an infection prevalence of only 12% was observed in snails based on cercarial shedding. While 47% of the snails were PCR-positive for the 500 bp ITS fragment, which was predicted to indicate infection with S. mansoni, sequence data demonstrated that these bands are not species-specific and can be amplified from other trematode infections. In addition, a 1000 bp band was amplified in 14% of samples, which was identified as a trematode in the family Derogenidae.The results support the previous assumption that B. pfeifferi snails may be involved in transmitting schistosomiasis in the area but suggest that the community structure of both snails and trematodes may be more complicated than previously thought. This emphasises the importance of confirming species identifications using sequencing, rather than relying only on PCR-based diagnostics or cercarial shedding.

Project description:Background: Schistosomiasis 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 for Biomphalaria pfeifferi, the most important vector for Schistosoma mansoni in Africa. We used Illumina technology to explore how field-derived B. pfeifferi, either uninfected or harboring cercariae-producing S. mansoni sporocysts, respond to a sublethal treatment 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 treated with niclosamide.Principal findings: Cercariae-producing sporocysts within snails treated with niclosamide express ~68% of the genes in the S. mansoni genome, as compared to 66% expressed by intramolluscan stages of S. mansoni in snails not treated with niclosamide. Niclosamide does not disable sporocysts nor does it seem to provoke from them distinctive responses associated with detoxifying a xenobiotic. For uninfected B. 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/significance: This study helps define the transcriptomic responses of an important and under-studied schistosome vector to S. mansoni sporocysts, to niclosamide, and to both in combination. It suggests the response of S. mansoni sporocysts 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.

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Establishment of Biomphalaria tenagophila snails in Europe.

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