Project description:Background: The parasitic trematode Schistosoma mansoni is one of the major causative agents of human schistosomiasis, which afflicts 200 million people worldwide. Praziquantel is still the only drug used for schistosomiasis treatment and reduction in drug efficiency has prompting the search for new therapeutic compounds against this disease. Our group has demonstrated that heme crystallization into hemozoin (Hz) within S. mansoni gut is a major heme detoxification route involving lipid droplets in this process and acting as a potential chemotherapeutical target. In the present work, we investigated the effects of the antimalarial quinine (QN) in a murine schistosomiasis model by using a combination of biochemical, cell biology and molecular biology approaches. Methodology/Principal Findings: Treatment of S. mansoni-infected female Swiss mice with daily intraperitoneal injections of QN (75mg/kg/day) from 11th to 17th day after infection decreased not only total, males and females worm burden (46.2 %-51.0 %), eggs production, but also the granulomatous reaction to parasite eggs trapped in the liver. These effects correlated with a significant impairment of Hz production (40%) specifically in S. mansoni females, being parallel to remarkable ultrastructural changes in female worms, particularly in the gut epithelium. Microarray gene expression analysis indicated that QN treatment increased the expression of transcripts related to musculature, protein synthesis and repair mechanisms. Conclusions: The overall significant reduction in several disease burden parameters by QN treatment indicates that interference of Hz formation in S. mansoni is a valid chemotherapeutical target for development of new antischistosomal drugs.
Project description:Schistosomiasis affects over 250 million people worldwide and is caused by trematodes of the genus Schistosoma including the species Schistosoma mansoni. Praziquantel (PZQ) is the most widely available and implemented drug for this disease, and is produced as an racematic mixture composed of the enantiomers, R-PZQ and S-PZQ. In this study we examined the gene expression profiles of 49 day male S. mansoni after 18 hour treatment with R-PZQ, S-PZQ or control (1% DMSO). These results provide insight into the effect of PZQ enantiomers against male S. mansoni.
Project description:We distrupted the expression of the Schistosoma mansoni zfp-1-1 gene using RNA interference and examined the transcriptional effects by illumina sequencing
Project description:Transcriptional profiling using two subsequent developmental stages of Schistosoma mansoni (Egg vs. Miracidium; Cercaria vs. 7-days-old Schistosomulum; 7-days-old Schistosomulum vs. Adult worms
Project description:Schistosoma mansoni is the causative agent of schistosomiasis, an endemic neglected tropical disease that affects the human population. Recently, newer versions of the genome and transcriptome have been published, with the Sanger Institute leading both the original publication of the genome as well as the further upgrade. However, little is known about the regulatory elements found in the genome, i.e. promoters. Identification of these elements is key for the understanding of mechanisms of regulation of gene expression in this parasitic helminth.
