Schistosoma mansoni functional genomics histone modifications ChIP seq
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina MiSeq
ORGANISM(S): Schistosoma mansoni
SUBMITTER:
PROVIDER: E-ERAD-96 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Schistosomiasis is one of the most socioeconomically harmful neglected tropical diseases in the world. It occurs following infection from parasites of the Schistosoma genus, such as Schistosoma mansoni, which must transition within a molluscan and mammalian host to survive. Previous chemical analyses of schistosome-molluscan interactions indicate that schistosomes orientate towards potential hosts partially through chemosensation, displaying a preference for naïve (uninfected) hosts. Recent advances in proteomic techniques enable sophisticated comparative analyses between infected and naïve snail host proteins. This study aimed to compare the snail-conditioned water (SCW) released by F1 resistant, infected and naïve Biomphalaria glabrata to identify potential attractants and deterrents.
2019-09-26 | PXD015129 | Pride
Project description:Schistosomiasis is a chronic neglected tropical disease caused by digenetic parasitic flatworms of the genus Schistosoma. The disease is estimated to affect over 206 million people, the majority of whom live in Africa where Schistosoma mansoni and Schistosoma japonicum are the major causative agents. While a number of drugs have been used to treat schistosomiasis, praziquantel (PZQ) is the only one that is widely available, relatively cheap, and easy to use. The reliance on a single drug for the treatment of such a prevalent disease is a cause for concern due to the potential for resistance to render PZQ ineffective. In this study we examine the transcriptome of three generations of a laboratory strain of S. mansoni (PR1) whose susceptibility to PZQ has been diminished across 9 passages through exposure to increasing sub-lethal doses of the drug. Miracidial susceptibility was significantly reduced after exposure to 2 x 50 mg/Kg PZQ during the first passage. Susceptibility of worms in vivo was first assessed during passage 5 when mice infected with PZQ-selected schistosomes were dosed with a lethal dose of 3 x 300 mg/Kg PZQ resulting in only a 10% reduction in worm number compared to control treatment. The emergence of reduced sensitivity was marked by a shift in sex ratio from a predominantly male to female population, a reduction in the length of females and ultimately the loss of the PZQ-selected line after passage 9, perhaps due to a selection induced fitness cost. Analysis of differentially regulated transcripts did not suggest that any particular gene product or pathway was associated with drug resistance suggesting either a loss of function mutation to a single gene or an epistatic interaction of multiple gene products.
2019-02-26 | GSE120682 | GEO
Project description:Schistosoma mansoni is a flatworm that causes schistosomiasis, a neglected tropical disease that affects over 200 million people worldwide. New therapeutic targets are needed with only one drug available for treatment and no vaccine. Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides with low or no protein-coding potential. In other organisms, they have been shown as involved with reproduction, stem cell maintenance and drug resistance, and they tend to exhibit tissue-specific expression patterns. S. mansoni expresses thousands of lncRNA genes; however, the cell type expression patterns of lncRNAs in the parasite remain uncharacterized. Here, we have re-analyzed public single-cell RNA-sequencing (scRNA-seq) data obtained from adult S. mansoni to identify the lncRNAs signature of adult schistosome cell types. A total of 8023 lncRNAs (79% of all lncRNAs) was detected. Analyses of the lncRNAs expression profiles in the cells using statistically stringent criteria were performed to identify 74 lncRNA gene markers of cell clusters. Male gamete and tegument lineage clusters contained most of the cluster-specific lncRNA markers. We also identified lncRNA markers of specific neural clusters. Whole-mount in situ hybridization (WISH) and double fluorescence in situ hybridization were used to validate the cluster-specific expression of 13 out of 16 lncRNA gene markers (81%) in the male and female adult parasite tissues; for one of these 16 gene loci, probes for two different lncRNA isoforms were used, which showed differential isoforms usage in testis and ovary. An atlas of the expression profiles across the cell clusters of all lncRNAs detected in our analysis is available as a public website resource. The results presented here give strong support to a tissue-specific expression and to a regulated expression program of lncRNAs in S. mansoni. This will be the basis for further exploration of lncRNA genes as potential therapeutic targets.
2022-10-01 | GSE207933 | GEO
Project description:Background: The parasitic trematode Schistosoma mansoni is one of the major causative agents of human schistosomiasis, which afflicts 200 million people worldwide. Praziquantel is still the only drug used for schistosomiasis treatment and reduction in drug efficiency has prompting the search for new therapeutic compounds against this disease. Our group has demonstrated that heme crystallization into hemozoin (Hz) within S. mansoni gut is a major heme detoxification route involving lipid droplets in this process and acting as a potential chemotherapeutical target. In the present work, we investigated the effects of the antimalarial quinine (QN) in a murine schistosomiasis model by using a combination of biochemical, cell biology and molecular biology approaches. Methodology/Principal Findings: Treatment of S. mansoni-infected female Swiss mice with daily intraperitoneal injections of QN (75mg/kg/day) from 11th to 17th day after infection decreased not only total, males and females worm burden (46.2 %-51.0 %), eggs production, but also the granulomatous reaction to parasite eggs trapped in the liver. These effects correlated with a significant impairment of Hz production (40%) specifically in S. mansoni females, being parallel to remarkable ultrastructural changes in female worms, particularly in the gut epithelium. Microarray gene expression analysis indicated that QN treatment increased the expression of transcripts related to musculature, protein synthesis and repair mechanisms. Conclusions: The overall significant reduction in several disease burden parameters by QN treatment indicates that interference of Hz formation in S. mansoni is a valid chemotherapeutical target for development of new antischistosomal drugs.
2009-07-13 | GSE14751 | GEO
Project description:Interference of hemozoin formation in Schistosoma mansoni by quinine reduces experimental schistosomiasis
| PRJNA112241 | ENA
Project description:Schistosoma mansoni is one of the most common etiological agents responsible for the disease schistosomiasis. More than 200 million people suffer from this disease making it the most severe tropical disease after malaria in terms of morbidity. Praziquantel (PZQ) is the treatment of choice for schistosomiasis and has been used almost exclusively to treat the disease since the 1970s. However, while the drug is lethal for sexually mature schistosomes, it is ineffective against juveniles. Thus, while morbidity can be eased, a cure is difficult to achieve. As a result there is an urgent need to develop a new generation of anti-schistosomal drugs, a task that will be made easier by understanding the mechanism of action of PZQ. As yet, neither the molecule to which PZQ binds nor the means by which it kills mature schistosomes is known. The overarching aim of this study was to understand the molecular basis of PZQ sensitivity in S. mansoni. We believe that juvenile worms survive PZQ treatment in vivo due to the induction of, as yet, unidentified protective molecular pathways. To address this hypothesis juvenile and adult PR1 S. mansoni were treated in vitro with sub-lethal concentrations of PZQ. mRNA was extracted from replicate samples, cRNA prepagreen and labeled with cyanine dyes for analysis using a 44K S. mansoni microarray. The data was then analyzed using Genespring. Our findings suggest that a number of genes associated with drug transport, iron homeostasis and apoptosis are induced in juvenile but not adult schistosomes and that this allows the juvenile worms to protect themselves against the lethal effects of PZQ long enough for the drug to be metabolized by the human host.
2011-05-27 | GSE29535 | GEO
Project description:Schistosomiasis, caused by infection with Schistosoma trematode parasites, is one of the deadliest neglected tropical diseases in the world. The Schistosoma lifecycle involves the miracidia infection of an intermediate molluscan host, such as Biomphalaria glabrata. Dispersing B. glabrata attractant chemicals has been considered a method of minimising host infections. The attractiveness of B. glabrata is known to be reduced following infection; however, it remained unclear how the duration of infection affects attractiveness. Identifying excretory-secretory proteins (ESPs) abundant in attractive snail conditioned water (SCW) may facilitate the identification of attractants. This study obtained SCW ESPs from naïve snails and at different time-points post-miracidia exposure (PME; 16h-, 1 week, 2 weeks and 3 weeks), to identify those ESPs mediating Schistosome mansoni miracidia behavioural changes. The ESPs were quantitatively identified from all SCW samples using a label-free proteomic method and genome-derived protein databases of B. glabrata and S. mansoni. We found that changes in miracidia behaviour were similar upon exposure to naïve and 3W-PME SCW, including increased circling and quantity of miracidia in the field of view. Of the ESPs identified, 21 were shared in SCW of naïve and 3W-PME, and considered attractant candidates, including acetylcholine-binding protein and immune-related proteins such as biomphalysins and thioester-containing protein 1. Some biological processes were exclusive to attractant candidates, including obsolete pathogenesis and transmembrane transport activity. This suggests that compromised production of these proteins may diminish host attractiveness to miracidia. Additionally, several immune proteins were identified exclusively at 16-PME and 1W-PME, providing further information into changing B. glabrata immune responses throughout infection. These findings provide a list of attractant candidates to potentially decrease B. glabrata infection and minimise schistosomiasis.
2022-10-03 | PXD031989 | Pride
Project description:The body’s defense against schistosome infection can take many forms. For example, upon developing acute schistosomiasis, patients often have fever coinciding with larval maturation, migration and early oviposition. As the infection becomes established, the parasite comes under oxidative stress generated by the host immune system. The most common treatment for schistosomiasis is the anti-helmenthic drug praziquantel. Its effectiveness, however, is limited due to its inability to kill schistosomes 2 - 4 weeks post-infection. Clearly there is a need for new anti-schistosomal drugs. We hypothesize that gene products expressed as part of a protective response against heat and/or oxidative stress are potential therapeutic targets for future drug development. Using a 12,166 element oligonucleotide microarray to characterize Schistosoma mansoni genes induced by heat and oxidative stress we found that 1,878 Schistosoma mansoni elements were significantly induced by heat stress. These included previously reported heat-shock genes expressing homologs of HSP40, HSP70 and HSP86. One thousand and one elements were induced by oxidative stress including those expressing homologs of superoxide dismutase, glutathione peroxidase and aldehyde dehydrogenase. Seventy-two elements were common to both stressors that could potentially be exploited in the development of novel anti-schistosomal therapeutics. Keywords: Stress response, time course
2008-08-25 | GSE11706 | GEO
Project description:Schistosomiasis affects over 250 million people worldwide and is caused by trematodes of the genus Schistosoma including the species Schistosoma mansoni. Praziquantel (PZQ) is the most widely available and implemented drug for this disease, and is produced as an racematic mixture composed of the enantiomers, R-PZQ and S-PZQ. In this study we examined the gene expression profiles of 49 day male S. mansoni after 18 hour treatment with R-PZQ, S-PZQ or control (1% DMSO). These results provide insight into the effect of PZQ enantiomers against male S. mansoni.
2023-04-22 | GSE114506 | GEO
Project description:The body’s defense against schistosome infection can take many forms. For example, upon developing acute schistosomiasis, patients often have fever coinciding with larval maturation, migration and early oviposition. As the infection becomes established, the parasite comes under oxidative stress generated by the host immune system. The most common treatment for schistosomiasis is the anti-helmenthic drug praziquantel. Its effectiveness, however, is limited due to its inability to kill schistosomes 2 - 4 weeks post-infection. Clearly there is a need for new anti-schistosomal drugs. We hypothesize that gene products expressed as part of a protective response against heat and/or oxidative stress are potential therapeutic targets for future drug development. Using a 12,166 element oligonucleotide microarray to characterize Schistosoma mansoni genes induced by heat and oxidative stress we found that 1,878 Schistosoma mansoni elements were significantly induced by heat stress. These included previously reported heat-shock genes expressing homologs of HSP40, HSP70 and HSP86. One thousand and one elements were induced by oxidative stress including those expressing homologs of superoxide dismutase, glutathione peroxidase and aldehyde dehydrogenase. Seventy-two elements were common to both stressors that could potentially be exploited in the development of novel anti-schistosomal therapeutics. Keywords: Stress response, time course Eight samples performed in duplicate for each temperature and oxidative stresses at time points 0, 30, 60, and 240 min over a common reference sample for each stress
2008-08-25 | E-GEOD-11706 | biostudies-arrayexpress