Mass Spectrometric Analysis of the Schistosoma m ansoni Tegumental Sub-proteome
Department of Biochemistry and Cell Biology (DBC), Utrecht University, Utrecht, Utrecht, Netherlands Journal of Proteome Research
(Impact Factor: 4.25).
06/2005; 4(3):958-66. DOI: 10.1021/pr050036w
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.
Available from: Rosimeire Nunes De Oliveira
- "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). "
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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.
Available from: Terry W Spithill
- "j Young et al. (2011(based on transcriptome data only; confirmed sequences present in transcriptome). k vanBalkom et al. (2005). l Haçariz et al. (2012). "
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ABSTRACT: The development of a vaccine for Fasciola spp. in livestock is a challenge and would be advanced by harnessing our knowledge of acquired immune mechanisms expressed by resistant livestock against fluke infection. Antibody-dependent cell-mediated cytotoxicity directed to the surface tegument of juvenile/immature flukes is a host immune effector mechanism, suggesting that antigens on the surface of young flukes may represent prime candidates for a fluke vaccine. A Type 1 immune response shortly after fluke infection is associated with resistance to infection in resistant sheep, indicating that vaccine formulations should attempt to induce Type 1 responses to enhance vaccine efficacy. In cattle or sheep, an optimal fluke vaccine would need to reduce mean fluke burdens in a herd below the threshold of 30 - 54 flukes to ensure sustainable production benefits. Fluke infection intensity data suggest that vaccine efficacy of approximately 80% is required to reduce fluke burdens below this threshold in most countries. With the increased global prevalence of triclabendazole-resistant F. hepatica, it may be commercially feasible in the short term to introduce a fluke vaccine of reasonable efficacy that will provide economic benefits for producers in regions where chemical control of new drug-resistant fluke infections is not viable. Commercial partnerships will be needed to fast-track new candidate vaccines using acceptable adjuvants in relevant production animals, obviating the need to evaluate vaccine antigens in rodent models.
- "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. "
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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.
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