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

Gobert, Geoffrey N., Tran, Mai H., Moertel, Luke, Mulvenna, Jason, Jones, Malcolm K., McManus, Donald P., and Loukas, Alex (2010) Transcriptional changes in Schistosoma mansoni during early schistosomula development and in the presence of erythrocytes. PLoS Neglected Tropical Disease, 4 (2). e600. pp. 1-13.

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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.

Item ID: 28638
Item Type: Article (Research - C1)
ISSN: 1935-2735
Keywords: complementary DNA; messenger RNA; serine proteinase inhibitor; tetraspanin; article; bone development; cell adhesion; cercaria (trematode larva); controlled study; DNA microarray; erythrocyte; fatty acid transport; gene identification; gene silencing; genetic transcription; integument; iron metabolism; nonhuman; nucleotide sequence; polymerase chain reaction; protein degradation; Schistosoma mansoni; Schistosomulum; stress; sugar transport; upregulation; animal; comparative study; gene; gene expression regulation; genetics; growth, development and aging; human; mouse; parasitology; animals; erythrocytes; gene expression regulation, developmental; genes; helminth; humans; mice; oligonucleotide array sequence analysis; Schistosoma mansoni; up-regulation
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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: 496600 and 290247
Date Deposited: 19 Aug 2013 02:55
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110803 Medical Parasitology @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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