Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of Schistosoma mansoni cercariae using genomic DNA as an indirect reference for identifying gender associated transcripts in morphologically identical but chromosomally distinct cercariae

ABSTRACT: Use of genomic DNA as an indirect reference for identifying gender associated transcripts in morphologically identical, but chromosomally distinct, Schistosoma mansoni cercariae

ORGANISM(S): Schistosoma mansoni

SUBMITTER: Jennifer Fitzpatrick

PROVIDER: E-MEXP-1259 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Background: Treatment and morbidity control of schistosomiasis relies on a single drug, praziquantel. Therefore, there is a pressing need to explore the effects of PZQ on the parasites at the molecular level and to pursue alternative and/or or synergistic drugs against schistosomiasis. Methodology: We used a custom-designed Schistosoma mansoni oligo-microarray to explore the effects of a sublethal dose of praziquantel on S. mansoni adult worms’ gene expression. We used functional analysis of gene interaction networks to identify differentially expressed genes that are known targets of other drugs already tested in humans for diverse disease conditions. Omeprazole, a proton pump inhibitor drug that is widely prescribed, was tested in combination with praziquantel. We comparatively assessed the efficacy of praziquantel or omeprazole alone and in combination against S. mansoni adult worms in vitro over a period of 120 hours. Principal Findings: We identified sets of genes that were affected by praziquantel on both paired and unpaired females, however with opposite gene expression patterns (up-regulated in paired and down-regulated in unpaired females), indicating that the transcriptomics changes induced by praziquantel are heavily influenced by the mating status. We also identified genes that were similarly affected by praziquantel in males and females. The use of sublethal doses of praziquantel together with omeprazole showed a significantly enhanced worm mortality in vitro compared to praziquantel alone, thus evidencing a synergic effect. Conclusions: Functional analysis of gene interaction networks is an important approach to identify genes whose expression is affected by one drug and that are at the same time known targets of other drugs already tested in humans for diverse disease conditions, thus pointing the latter as possible synergic drugs. Combined treatment with omeprazol increases the efficacy of praziquantel against S. mansoni adult worms in vitro, and additional in vivo studies are warranted. Two-condition experiment, PZQ-treated vs. untreated . Biological replicates: 2 with dye-swap

Project description:Protein variation in blood-dwelling schistosome worms generated by differential splicing of micro-exon gene transcripts. The infective schistosome cercaria develops from an undifferentiated germ ball within the daughter sporocyst in the molluscan host, during which considerable morphological development and synthesis of proteins essential for infection occurs. The free-living, non-feeding cercaria is notable for its swimming and host location behaviour. On contact with host skin it rapidly penetrates, replaces its tegument surface membranes, and begins body remodelling, before crossing the dermis to exit the skin via a blood vessel. Such a ‘violent’ transition from snail to fresh water to mammalian host should be accompanied by remarkable changes in the patterns of gene expression. All gene models from version E of the S. mansoni genome (www.GeneDB.org) were incorporated into a 350K feature Roche-NimbleGen, high-density oligonucleotide array. From a map-ordered list, every 13th 50mer was chosen as a probe. Double-stranded cDNA from three biological replicates each of germ balls, cercariae, and day 3 schistosomula was hybridised to the array without amplification. Statistical analysis was carried out using programmes from the Bioconductor suite (Gentleman et al. 2004 Genome Biol 5(10):R80). More than 1000 loci were shown to be differentially expressed in each of the comparisons between the three life cycle stages. Gene ontology (GO) analysis was then carried out to discover the categories enriched in each stage. In addition custom categories based on biological function (e.g. stress response) or parasite tissue (e.g. tegument) were analysed. Three biological replicates each of germ balls, cercariae, day 3 in vitro cultured schistosomula, and eggs were used. No technical replicates were included. This is the first genome-wide microarray platform for S. mansoni. It was used to investigate the gene expression patterns of the above lifecycle stages. The first three are the stages before, during and after penetration of mammalian host skin.

Dataset Information

Transcription profiling of Schistosoma mansoni cercariae using genomic DNA as an indirect reference for identifying gender associated transcripts in morphologically identical but chromosomally distinct cercariae

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