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Antiprotozoal Agents

Antiprotozoal Agents

Leishmaniasis is a widespread parasitic disease caused by several Leishmania species. It affects millions of people each year and remains a major public health problem in endemic regions. First-line treatment relies on pentavalent antimonials, including meglumine antimoniate and sodium stibogluconate. Even so, how these drugs work has not been fully clear, especially their interaction with parasite-specific biochemical pathways. One key target is trypanothione reductase (TR), an enzyme that...

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Methods to Investigate the Regulatory Role of Small RNAs and Ribosomal Occupancy of Plasmodium falciparum

Methods to Investigate the Regulatory Role of Small RNAs and Ribosomal Occupancy of Plasmodium falciparum

Published on: December 4, 2015

Anti-schistosomal intervention targets identified by lifecycle transcriptomic analyses.

Jennifer M Fitzpatrick¹, Emily Peak, Samirah Perally

¹Department of Pathology, University of Cambridge, Cambridge, United Kingdom.

Plos Neglected Tropical Diseases

|November 4, 2009

Summary

This study used bioinformatics to analyze schistosome gene expression across development, identifying potential new drug targets for schistosomiasis control. The approach combined statistical and network analyses to reveal key transcriptional programs essential for parasite survival.

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Area of Science:

Parasitology
Bioinformatics
Molecular Biology

Background:

Novel anthelmintic drug and vaccine targets are crucial for combating parasitic diseases like schistosomiasis, which often rely on limited control strategies.
Understanding helminth development at the transcriptional level is key to identifying essential molecules for parasite-host interactions.

Purpose of the Study:

To develop and apply a combinatorial, bioinformatics-led approach using statistical and network analyses of transcriptomic data.
To identify novel immunoprophylactic and therapeutic lead targets against schistosomiasis.

Main Methods:

Utilized a Schistosoma mansoni oligonucleotide DNA microarray with 37,632 elements for gene expression profiling across 15 lifecycle stages.
Employed statistical analyses to identify differentially expressed genes and network analyses coupled with Gene Ontology enrichment for higher-order relationship discovery.

Main Results:

Identified 973 differentially expressed gene products related to asexual and sexual development, and sexual dimorphism.
Discovered 338 constitutively expressed gene products essential for lifecycle progression, including 41 with no known similarity outside Platyhelminthes.
Network analysis revealed 387 clusters with novel developmentally regulated classes, including 294 unique transcripts, undetectable by statistical methods alone.

Conclusions:

Combined statistical and network analyses provide a comprehensive characterization of schistosome development.
Highlighted key transcriptional programs essential for parasite lifecycle progression.
Identified numerous anti-schistosomal candidate molecules, including G-protein coupled receptors, tetraspanins, and the netrin/netrin receptor complex.