Developmental Regulation of Genes Encoding Universal Stress Proteins in Schistosoma mansoni

Abstract

The draft nuclear genome sequence of the snail-transmitted, dimorphic, parasitic, platyhelminth Schistosoma mansoni revealed eight genes encoding proteins that contain the Universal Stress Protein (USP) domain. Schistosoma mansoni is a causative agent of human schistosomiasis, a severe and debilitating Neglected Tropical Disease (NTD) of poverty, which is endemic in at least 76 countries. The availability of the genome sequences of Schistosoma species presents opportunities for bioinformatics and genomics analyses of associated gene families that could be targets for understanding schistosomiasis ecology, intervention, prevention and control. Proteins with the USP domain are known to provide bacteria, archaea, fungi, protists and plants with the ability to respond to diverse environmental stresses. In this research investigation, the functional annotations of the USP genes and predicted nucleotide and protein sequences were initially verified. Subsequently, sequence clusters and distinctive features of the sequences were determined. A total of twelve ligand binding sites were predicted based on alignment to the ATP-binding universal stress protein from Methanocaldococcus jannaschii. In addition, six USP sequences showed the presence of ATP-binding motif residues indicating that they may be regulated by ATP. Public domain gene expression data and RT-PCR assays confirmed that all the S. mansoni USP genes were transcribed in at least one of the developmental life cycle stages of the helminth. Six of these genes were up-regulated in the miracidium, a free-swimming stage that is critical for transmission to the snail intermediate host. It is possible that during the intra-snail stages, S. mansoni gene transcripts for universal stress proteins are low abundant and are induced to perform specialized functions triggered by environmental stressors such as oxidative stress due to hydrogen peroxide that is present in the snail hemocytes. This report serves to catalyze the formation of a network of researchers to understand the function and regulation of the universal stress proteins encoded in genomes of schistosomes and their snail intermediate hosts.

Inferences on the biochemical and environmental regulation of universal stress proteins from Schistosomiasis parasites

“…The developmental stage expression profiles of the selected Schistosoma USP genes were extracted from our previous publication12 for S. mansoni . In the case of S. japonicum , expression profiles were from the SjTPdb, an integrated transcriptome and proteome database and analysis platform for S. japonicum 55.…”

“…The USPs are known to function during unfavorable environmental conditions, including the life cycle developmental stages in Schistosoma spp 10–12. Though data on gene expression is available for genes encoding USPs (USP genes), their biochemical and environmental regulation are incompletely understood 10–19.…”

“…Genes encoding USPs have not been identified in the human genome, thus making them attractive as drug targets 21. In a previous report,12 we analyzed the developmental expression of eight USP genes predicted from the S. mansoni genome. In the case of S. japonicum , multiple research investigations have detected developmental stage expression of USP genes 10,11,16…”

“…A common aspect of these environment-inducing stresses is that they result in proteins with nonnative conformations 26. Inducible stress tolerance has increasingly been understood to result from numerous molecular mechanisms, such as heat shock proteins (Hsps) and USPs 12,27–31…”

Tandem repeat recombinant proteins as potential antigens for the sero-diagnosis of Schistosoma mansoni infection

“…TR genes were amplified using Hot start Ex Taq DNA polymerase (Takara). S. mansoni alphatubulin gene was used as a constitutively expressed positive control gene to access the PCR reaction; specific primers targeting a 200 basepair (bp) length of alpha-tubulin were used for the reaction [50]. Using cDNA from both adult worms and eggs as PCR templates, the amplified TR gene domains were separated on 1.5% agarose gel, the positive band corresponding to one or two periods of the tandem repeat were cut from the gel and purified using a QIAQuick gel extraction kit (Qiagen, Hombrechikon, Switzerland).…”