Schistosoma mansoni is a parasitic worm that lives in the blood vessels of its host. We mapped the S. mansoni tegumental outer-surface structure proteome by 1D SDS-PAGE and LC-MS/MS and an EST-database from the ongoing genome-sequencing project. We identified 740 proteins of which 43 were tegument-specific. Many of these proteins show no homology to any nonschistosomal protein, demonstrating that the schistosomal outer-surface comprises specific and unique proteins, likely to be critical for parasite survival.
"To better understand some of these mechanisms, modern analytical approaches, e.g. chromatographic techniques combined with MS, have been employed for chemical characterisation of adult schistosomes and PZQ metabolites in the host (Meier and Blaschke, 2000, 2001; van Balkom et al., 2005). More recently, MALDI-MS has been applied as the main analytical tool (Frank et al., 2012). "
[Show abstract][Hide abstract] ABSTRACT: Finding specific molecular targets and the mechanism of action of praziquantel in the treatment of schistosomiasis remains a challenging task. Our efforts were focused on obtaining further information
on worm composition before and after exposure to praziquantel in the treatment of schistosomiasis to
elucidate the potential sites of action of this drug. Evidence indicates that the lipid bilayer is changed
by treatment with praziquantel. Following this rationale, we employed a mass spectrometry 31
imaging-based approach that helped to characterise lipids in specific locations, which are directly 32
involved in the biochemical pathways of the BH strain of Schistosoma mansoni, as well as differentiating
the molecular response that each worm sex presents in vivo. Our findings demonstrated significant differences between the chemical markers found in adult worms before and after praziquantel exposure,
especially in phospholipids, which were predominantly identified as chemical markers in all samples.
Results also indicate that distinct molecular pathways in both male and female worms could be differentially affected by praziquantel treatment. These data shine new light on the mechanism of action of praziquantel, taking a further step towards its full understanding.
International Journal for Parasitology 03/2015; · 3.87 Impact Factor
"Based on the purpose of proteomics researches, schistosomal samples ought to be prepared in different ways. So far, schistosomal proteomics has been applied to the investigation and comparison of protein compositions in various developmental stages (Curwen et al., 2004; Liu et al., 2006) or between different genders (Cheng et al., 2005; Liu et al., 2006) and the worm proteins might be pre-fractioned accordingly, e.g., soluble membrane protein (Curwen et al., 2004; Cheng et al., 2005), tegumental fractions (Van Balkom et al., 2005; Braschi et al., 2006; Braschi and Wilson, 2006; Liu et al., 2006; Mulvenna et al., 2010; Castro-Borges et al., 2011), secreted antigens (Knudsen et al., 2005; Curwen et al., 2006; Liu et al., 2009), gut contents (Delcroix et al., 2007), etc. "
[Show abstract][Hide abstract] ABSTRACT: Schistosomiasis, caused by dioecious flatworms in the genus Schistosoma, is torturing people from many developing countries nowadays and frequently leads to severe morbidity and mortality of the patients. Praziquantel based chemotherapy and morbidity control for this disease adopted currently necessitate viable and efficient diagnostic technologies. Fortunately, those "-omics" researches, which rely on high-throughput experimental technologies to produce massive amounts of informative data, have substantially contributed to the exploitation and innovation of diagnostic tools of schistosomiasis. In its first section, this review provides a concise conclusion on the progresses pertaining to schistosomal "-omics" researches to date, followed by a comprehensive section on the diagnostic methods of schistosomiasis, especially those innovative ones based on the detection of antibodies, antigens, nucleic acids, and metabolites with a focus on those achievements inspired by "-omics" researches. Finally, suggestions about the design of future diagnostic tools of schistosomiasis are proposed, in order to better harness those data produced by "-omics" studies.
Frontiers in Microbiology 06/2014; 5:313. DOI:10.3389/fmicb.2014.00313 · 3.99 Impact Factor
"SmAP is a ∼62 kDa glycosylphosphatidylinositol (GPI) anchored protein that is expressed in the tegument and internal tissues of the adult worms (Bhardwaj & Skelly, 2011; Cesari, 1974; Dusanic, 1959; Levi-Schaffer et al., 1984; Morris & Threadgold, 1968; Pujol et al., 1990). The protein can be cleaved from cultured schistosomula (Espinoza et al., 1988) and from adult worms (Castro-Borges et al., 2011) by the phosphatidylinositol-cleaving enzyme—phosphatidylinositol-specific phospholipase C. Tegumental proteomic analysis confirms that SmAP is found in the schistosome surface membranes (Braschi et al., 2006; van Balkom et al., 2005) and is available for surface biotinylation (Braschi & Wilson, 2006). "
[Show abstract][Hide abstract] ABSTRACT: Schistosomes are parasitic worms that can survive in the hostile environment of the human bloodstream where they appear refractory to both immune elimination and thrombus formation. We hypothesize that parasite migration in the bloodstream can stress the vascular endothelium causing this tissue to release chemicals alerting responsive host cells to the stress. Such chemicals are called damage associated molecular patterns (DAMPs) and among the most potent is the proinflammatory mediator, adenosine triphosphate (ATP). Furthermore, the ATP derivative ADP is a pro-thrombotic molecule that acts as a strong activator of platelets. Schistosomes are reported to possess at their host interactive tegumental surface a series of enzymes that could, like their homologs in mammals, degrade extracellular ATP and ADP. These are alkaline phosphatase (SmAP), phosphodiesterase (SmNPP-5) and ATP diphosphohydrolase (SmATPDase1). In this work we employ RNAi to knock down expression of the genes encoding these enzymes in the intravascular life stages of the parasite. We then compare the abilities of these parasites to degrade exogenously added ATP and ADP. We find that only SmATPDase1-suppressed parasites are significantly impaired in their ability to degrade these nucleotides. Suppression of SmAP or SmNPP-5 does not appreciably affect the worms' ability to catabolize ATP or ADP. These findings are confirmed by the functional characterization of the enzymatically active, full-length recombinant SmATPDase1 expressed in CHO-S cells. The enzyme is a true apyrase; SmATPDase1 degrades ATP and ADP in a cation dependent manner. Optimal activity is seen at alkaline pH. The Km of SmATPDase1 for ATP is 0.4 ± 0.02 mM and for ADP, 0.252 ± 0.02 mM. The results confirm the role of tegumental SmATPDase1 in the degradation of the exogenous pro-inflammatory and pro-thrombotic nucleotides ATP and ADP by live intravascular stages of the parasite. By degrading host inflammatory signals like ATP, and pro-thrombotic signals like ADP, these parasite enzymes may minimize host immune responses, inhibit blood coagulation and promote schistosome survival.
Louise Jank, Magda Targa Martins, Juliana Bazzan Arsand, Rodrigo Barcellos Hoff, Fabiano Barreto, Tânia Mara Pizzolato
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