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Transcriptional changes in Schistosoma mansoni during early schistosomula development and in the presence of erythrocytes.


ABSTRACT: BACKGROUND: Schistosomes cause more mortality and morbidity than any other human helminth, but control primarily relies on a single drug that kills adult worms. The newly transformed schistosomulum stage is susceptible to the immune response and is a target for vaccine development and rational drug design. METHODOLOGY/PRINCIPAL FINDINGS: To identify genes which are up-regulated during the maturation of Schistosoma mansoni schistosomula in vitro, we cultured newly transformed parasites for 3 h or 5 days with and without erythrocytes and compared their transcriptional profiles using cDNA microarrays. The most apparent changes were in the up-regulation of genes between 3 h and 5 day schistosomula involved in blood feeding, tegument and cytoskeletal development, cell adhesion, and stress responses. The most highly up-regulated genes included a tegument tetraspanin Sm-tsp-3 (1,600-fold up-regulation), a protein kinase, a novel serine protease and serine protease inhibitor, and intestinal proteases belonging to distinct mechanistic classes. The inclusion of erythrocytes in the culture medium resulted in a general but less pronounced increase in transcriptional activity, with the highest up-regulation of genes involved in iron metabolism, proteolysis, and transport of fatty acids and sugars. CONCLUSIONS: We have identified the genes that are up-regulated during the first 5 days of schistosomula development in vitro. Using a combination of gene silencing techniques and murine protection studies, some of these highly up-regulated transcripts can be targeted for future development of new vaccines and drugs.

SUBMITTER: Gobert GN 

PROVIDER: S-EPMC2817720 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Transcriptional changes in Schistosoma mansoni during early schistosomula development and in the presence of erythrocytes.

Gobert Geoffrey N GN   Tran Mai H MH   Moertel Luke L   Mulvenna Jason J   Jones Malcolm K MK   McManus Donald P DP   Loukas Alex A  

PLoS neglected tropical diseases 20100209 2


<h4>Background</h4>Schistosomes cause more mortality and morbidity than any other human helminth, but control primarily relies on a single drug that kills adult worms. The newly transformed schistosomulum stage is susceptible to the immune response and is a target for vaccine development and rational drug design.<h4>Methodology/principal findings</h4>To identify genes which are up-regulated during the maturation of Schistosoma mansoni schistosomula in vitro, we cultured newly transformed parasit  ...[more]

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