Dataset Information

Transcriptional responses of Biomphalaria pfeifferi and Schistosoma mansoni following exposure to niclosamide, with evidence for a synergistic effect on snails following exposure to both stressors.

ABSTRACT: 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.

SUBMITTER: Buddenborg SK

PROVIDER: S-EPMC6936870 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Transcriptional responses of Biomphalaria pfeifferi and Schistosoma mansoni following exposure to niclosamide, with evidence for a synergistic effect on snails following exposure to both stressors.

Buddenborg Sarah K SK Kamel Bishoy B Bu Lijing L Zhang Si-Ming SM Mkoji Gerald M GM Loker Eric S ES

PLoS neglected tropical diseases 20191216 12

<h4>Background</h4>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 ...[more]

PMID: 31841501

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Project description:Background: The full scope of the genes expressed by schistosomes during intramolluscan development has yet to be characterized. Understanding the gene products deployed by larval schistosomes in their snail hosts will provide insights into their establishment, maintenance, asexual reproduction, ability to castrate their hosts, and their prolific production of human-infective cercariae. Using the Illumina platform, the intramolluscan transcriptome of Schistosoma mansoni was investigated in field-derived specimens of the prominent vector species Biomphalaria pfeifferi at 1 and 3 days post infection (d) and from snails shedding cercariae. These S. mansoni samples were derived from the same snails used in our complementary B. pfeifferi transcriptomic study. We supplemented this view with microarray analyses of S. mansoni from B. glabrata at 2d, 4d, 8d, 16d, and 32d to highlight robust features of S. mansoni transcription, even when a different technique and vector species was used.Principal findings: Transcripts representing at least 7,740 (66%) of known S. mansoni genes were expressed during intramolluscan development, with the greatest number expressed in snails shedding cercariae. Many transcripts were constitutively expressed throughout development featuring membrane transporters, and metabolic enzymes involved in protein and nucleic acid synthesis and cell division. Several proteases and protease inhibitors were expressed at all stages, including some proteases usually associated with cercariae. Transcripts associated with G-protein coupled receptors, germ cell perpetuation, and stress responses and defense were well represented. We noted transcripts homologous to planarian anti-bacterial factors, several neural development or neuropeptide transcripts including neuropeptide Y, and receptors that may be associated with schistosome germinal cell maintenance that could also impact host reproduction. In at least one snail the presence of larvae of another digenean species (an amphistome) was associated with repressed S. mansoni transcriptional activity.Conclusions/significance: This in vivo study, emphasizing field-derived snails and schistosomes, but supplemented with observations from a lab model, provides a distinct view from previous studies of development of cultured intramolluscan stages from lab-maintained organisms. We found many highly represented transcripts with suspected or unknown functions, with connection to intramolluscan development yet to be elucidated.

Project description:BackgroundBiomphalaria pfeifferi is the world's most widely distributed and commonly implicated vector snail species for the causative agent of human intestinal schistosomiasis, Schistosoma mansoni. In efforts to control S. mansoni transmission, chemotherapy alone has proven insufficient. New approaches to snail control offer a way forward, and possible genetic manipulations of snail vectors will require new tools. Towards this end, we here offer a diverse set of genomic resources for the important African schistosome vector, B. pfeifferi.Methodology/principal findingsBased largely on PacBio High-Fidelity long reads, we report a genome assembly size of 772 Mb for B. pfeifferi (Kenya), smaller in size than known genomes of other planorbid schistosome vectors. In a total of 505 scaffolds (N50 = 3.2Mb), 430 were assigned to 18 large linkage groups inferred to represent the 18 known chromosomes, based on whole genome comparisons with Biomphalaria glabrata. The annotated B. pfeifferi genome reveals a divergence time of 3.01 million years with B. glabrata, a South American species believed to be similar to the progenitors of B. pfeifferi which undertook a trans-Atlantic colonization < five million years ago.Conclusions/significanceThe genome for this preferentially self-crossing species is less heterozygous than related species known to be preferential out-crossers; its smaller genome relative to congeners may similarly reflect its preference for selfing. Expansions of gene families with immune relevance are noted, including the FReD gene family which is far more similar in its composition to B. glabrata than to Bulinus truncatus, a vector for Schistosoma haematobium. Provision of this annotated genome will help better understand the dependencies of trematodes on snails, enable broader comparative insights regarding factors contributing to susceptibility/ resistance of snails to schistosome infections, and provide an invaluable resource with respect to identifying and manipulating snail genes as potential targets for more specific snail control programs.

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:There is increasing interest in the control and elimination of schistosomiasis. Little is known, however, about the likely effects of increasing water-body temperatures on transmission.We have developed an agent-based model of the temperature-sensitive stages of the Schistosoma and intermediate host snail life-cycles, parameterised using data from S. mansoni and Biomphalaria pfeifferi laboratory and field-based observations. Infection risk is calculated as the number of cercariae in the model, adjusted for their probability of causing infection.The number of snails in the model is approximately constant between 15-31°C. Outside this range, snail numbers drop sharply, and the snail population cannot survive outside the range 14-32°C. Mean snail generation time decreases with increasing temperature from 176 days at 14°C to 46 days at 26°C. Human infection risk is highest between 16-18°C and 1pm and 6-10pm in calm water, and 20-25°C and 12-4pm in flowing water. Infection risk increases sharply when temperatures increase above the minimum necessary for sustained transmission.The model suggests that, in areas where S. mansoni is already endemic, warming of the water at transmission sites will have differential effects on both snails and parasites depending on abiotic properties of the water-body. Snail generation times will decrease in most areas, meaning that snail populations will recover faster from natural population reductions and from snail-control efforts. We suggest a link between the ecological properties of transmission sites and infection risk which could significantly affect the outcomes of interventions designed to alter water contact behaviour--proposing that such interventions are more likely to reduce infection levels at river locations than lakes, where infection risk remains high for longer. In cooler areas where snails are currently found, increasing temperatures may significantly increase infection risk, potentially leading to new, high-intensity foci of infection.

Project description:Background: Biomphalaria pfeifferi is highly compatible with the widespread human-infecting blood fluke Schistosoma mansoni and transmits more cases of this parasite to people than any other snail species. For these reasons, B. pfeifferi is the world's most important vector snail for S. mansoni, yet we know relatively little at the molecular level regarding the interactions between B. pfeifferi and S. mansoni from early-stage sporocyst transformation to the development of cercariae.Methodology/principal findings: We sought to capture a portrait of the response of B. pfeifferi to S. mansoni as it occurs in nature by undertaking Illumina dual RNA-Seq on uninfected control B. pfeifferi and three intramolluscan developmental stages (1- and 3-days post infection and patent, cercariae-producing infections) using field-derived west Kenyan specimens. A high-quality, well-annotated de novo B. pfeifferi transcriptome was assembled from over a half billion non-S. mansoni paired-end reads. Reads associated with potential symbionts were noted. Some infected snails yielded fewer normalized S. mansoni reads and showed different patterns of transcriptional response than others, an indication that the ability of field-derived snails to support and respond to infection is variable. Alterations in transcripts associated with reproduction were noted, including for the oviposition-related hormone ovipostatin and enzymes involved in metabolism of bioactive amines like dopamine or serotonin. Shedding snails exhibited responses consistent with the need for tissue repair. Both generalized stress and immune factors immune factors (VIgLs, PGRPs, BGBPs, complement C1q-like, chitinases) exhibited complex transcriptional responses in this compatible host-parasite system.Significance: This study provides for the first time a large sequence data set to help in interpreting the important vector role of the neglected snail B. pfeifferi in transmission of S. mansoni, including with an emphasis on more natural, field-derived specimens. We have identified B. pfeifferi targets particularly responsive during infection that enable further dissection of the functional role of these candidate molecules.

Dataset Information

Transcriptional responses of Biomphalaria pfeifferi and Schistosoma mansoni following exposure to niclosamide, with evidence for a synergistic effect on snails following exposure to both stressors.

Publications

Transcriptional responses of Biomphalaria pfeifferi and Schistosoma mansoni following exposure to niclosamide, with evidence for a synergistic effect on snails following exposure to both stressors.

Similar Datasets

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