1. The Transcriptome Analysis of Strongyloides stercoralis L3i Larvae Reveals Targets for Intervention in a Neglected Disease.
- Author
-
Marcilla, Antonio, Garg, Gagan, Bernal, Dolores, Ranganathan, Shoba, Forment, Javier, Ortiz, Javier, Muñoz-Antolí, Carla, Dominguez, M. Victoria, Pedrola, Laia, Martinez-Blanch, Juan, Sotillo, Javier, Trelis, Maria, Toledo, Rafael, and Esteban, J. Guillermo
- Subjects
NEMATODE infections ,NEGLECTED diseases ,NUCLEOTIDE sequencing ,MOLECULAR biology ,TRANSCRIPTOMES ,ENDEMIC diseases - Abstract
Background: Strongyloidiasis is one of the most neglected diseases distributed worldwide with endemic areas in developed countries, where chronic infections are life threatening. Despite its impact, very little is known about the molecular biology of the parasite involved and its interplay with its hosts. Next generation sequencing technologies now provide unique opportunities to rapidly address these questions. Principal Findings: Here we present the first transcriptome of the third larval stage of S. stercoralis using 454 sequencing coupled with semi-automated bioinformatic analyses. 253,266 raw sequence reads were assembled into 11,250 contiguous sequences, most of which were novel. 8037 putative proteins were characterized based on homology, gene ontology and/or biochemical pathways. Comparison of the transcriptome of S. strongyloides with those of other nematodes, including S. ratti, revealed similarities in transcription of molecules inferred to have key roles in parasite-host interactions. Enzymatic proteins, like kinases and proteases, were abundant. 1213 putative excretory/secretory proteins were compiled using a new pipeline which included non-classical secretory proteins. Potential drug targets were also identified. Conclusions: Overall, the present dataset should provide a solid foundation for future fundamental genomic, proteomic and metabolomic explorations of S. stercoralis, as well as a basis for applied outcomes, such as the development of novel methods of intervention against this neglected parasite. Author Summary: Strongyloides stercoralis (Nematoda) is an important parasite of humans, causing Strongyloidiasis, considered as one of the most neglected diseases, affecting more than 100 million people worldwide. Chronic infections in endemic areas can be maintained for decades through the autoinfective cycle with the L3 filariform larvae. In these areas, misdiagnosis, inadequate treatment and the facilitation of hyperinfection syndrome by immunosupression are frequent and contribute to a high mortality rate. Among the affected areas, chronic patients have been described in the Valencian Mediterranean coastal region of Spain. Despite its serious impact, very little is known about this parasite and its relationship with its hosts at the molecular level, and more effective diagnostic tests and treatments are needed. Next generation sequencing technologies now provide unique opportunities to rapidly advance in these areas. In this study, we present the first transcriptome of S. stercoralis L3i using 454 sequencing followed by semi-automated bioinformatic analyses. Our study identifies 8037 putative proteins based on homology, gene ontology, and/or biochemical pathways, including putative excretory/secretory proteins as well as potential drug targets. The present dataset provides a useful resource and adds greatly to our understanding of a human parasite affecting both developed and developing countries. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF