title: 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.
  
  
  RESULTS
  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.
authors.affiliation: Division of Infectious Diseases, Queensland Institute of Medical Research, Queensland, Australia.
authors.forename: Geoffrey N
authors.initials: GN
authors.lastname: Gobert
authors.forename: Mai H
authors.initials: MH
authors.lastname: Tran
authors.forename: Luke
authors.initials: L
authors.lastname: Moertel
authors.forename: Jason
authors.initials: J
authors.lastname: Mulvenna
authors.forename: Malcolm K
authors.initials: MK
authors.lastname: Jones
authors.forename: Donald P
authors.initials: DP
authors.lastname: McManus
authors.forename: Alex
authors.initials: A
authors.lastname: Loukas
mesh_terms: D000818:Animals; D004912:Erythrocytes / Q000469:parasitology*; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D006801:Humans; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D012550:Schistosoma mansoni / Q000235:genetics* / Q000254:growth & development*; D015854:Up-Regulation