Trends in Parasitology
The molecular biology of schistosomes
Section snippets
Tropical scourge
As many people today are affected by schistosomiasis as were 50 years ago, although where these infected people live has changed during these five decades, following changes in socioeconomic and political events; residents of sub-Saharan Africa endure the heaviest burden [1]. Moreover, a recent meta-analysis indicates that the burden of schistosomiasis is far greater than previously estimated, in terms of anaemia, chronic pain, diarrhoea, exercise intolerance and undernourishment (in addition
Genome and transcriptome
Schistosome species that infect humans include Schistosoma mansoni, Schistosoma haematobium, Schistosoma japonicum and, to a lesser extent, Schistosoma intercalatum and Schistosoma mekongi. Of these, the African blood fluke S. mansoni and the Asian blood fluke S. japonicum have been characterized reasonably well at the genomic level. Schistosomes have comparatively large genomes, estimated to be ∼270 Mb for the haploid genome of S. mansoni, arrayed on seven pairs of autosomes and one pair of sex
Mobile genetic elements, other repetitive sequences and schistosome phylogeny
Between 40% and 60% of the schistosome genome seems to consist of repetitive sequences. Much of this repetitive component comprises mobile genetic elements that include the Merlin transposon, the SM-α SINE-like elements, long terminal repeat (LTR) retrotransposons such as Boudicca, and non-LTR retrotransposons, including SR2 and pido 14, 15, 16, 17, 18. As with other species, these mobile sequences have had a substantial influence on the evolution of the schistosome genome [19]. In addition,
Mitochondrial genome
Mitochondria accomplish the respiratory metabolism of eukaryote cells. The mitochondrial genomes of S. japonicum and S. mansoni have been sequenced, as have most of the mitochondrial genomes of Schistosoma malayensis, S. mekongi and S. haematobium, and sequences of informative loci from the mitochondrial genomes of several other flatworms are known [23]. The studies determining the sequences confirmed that the schistosome mitochondrial genome is small, circular and haploid, conforming to the
Signal transduction
In addition to functions predicted from transcriptomics analyses [8], many schistosome genes and proteins have been functionally characterized, including components of signal-transduction pathways. Much of the motivation for progress in research into signalling and the molecular biology of reproduction has been the understanding that female parasite development and reproduction are dependent on the presence of the male schistosome [24]. Genes that encode tegument-localized signal-transduction
Motility
Jones et al. [34] have reviewed the cytoskeleton and motor proteins at the surface of the human schistosomes, and their roles in surface maintenance and host–parasite interactions. Several genes and proteins associated with motility functions in schistosomes have been characterized in detail, including myosin, paramyosin, tropomyosin, actin, troponins and dynein light chains. Maule and co-workers have characterized neuropeptides that are central to signal transduction in the schistosome nervous
Nutrition
Schistosomes use amino acids from the digestion of host haemoglobin from ingested blood for growth, development and reproduction. Genes encoding haemoglobin-degrading hydrolases – including cathepsins B, C, D and L, and leucine aminopeptidase – and their recombinant forms and substrate preferences have been characterized 36, 37. Schistosome cells move amino acids and glucose across their surface membranes with the aid of transporter proteins that are localized in the parasite tegument 38, 39.
Molecular and cellular manipulation tools
Since Carter and Colley first reported on the availability of phage cDNA libraries [3], many other gene- and genome-manipulation tools for schistosome molecular genetics have been developed or deployed. These include bacterial artificial chromosome libraries containing manifold genome equivalents [43], gene microarrays [44], reporter systems for gene regulatory element analysis 45, 46, transcription factor analysis – including investigation of a Y-box-binding protein from S. mansoni [47] –
Drugs, vaccines and concluding remarks
Praziquantel (PZQ) is the drug of choice for treating all forms of schistosomiasis. Although PZQ was first used ∼25 years ago, the molecular basis of its antischistosomal action has not been elucidated fully. Greenberg et al. have characterized schistosome voltage-gated calcium channels and compared their molecular structures with homologous channels from other eukaryotes. These channels seem to have a key role in the action of PZQ [56]. The artemisinin derivative artemether also offers promise
Acknowledgements
I am a recipient of a Burroughs Wellcome Fund scholar award in molecular parasitology. Support from NIH/NIAID award number P50 AI39461–06A1 is gratefully acknowledged.
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2011, Experimental ParasitologyCitation Excerpt :Schistosome eggs across endothelial and mucosal barriers towards to the intestinal lumen, so that viable mature eggs can reach the outside environment with the host’s feces. Molecules secreted from eggs (Ashton et al., 2001) induce cytokine production (Brindley, 2005) and local inflammation, where inflammatory cells sustain egg passage (Doenhoff et al., 1978, 1986; Damian, 1987; Lenzi et al., 1987; Doenhoff, 1998; Brindley, 2005; Andrade, 2009). The lack of insulin in the diabetic mice might therefore have caused a lowering in the Th2 response, which is necessary for the peri-ovular granulomatous reactions (Kaplan et al., 1998) facilitating the passage of eggs through the intestine tissue.
Schistosome biology and proteomics: Progress and challenges
2007, Experimental ParasitologyCitation Excerpt :Third, schistosomes are multi-cellular eukaryotes containing distinct tissues, such as reproductive organs, secretory glands, etc., each containing a specific set of diverse cell types, for all of which a cell line is lacking that can be cultivated in vitro. Multiple methods have been developed for various schistosomal life-cycle stages to manipulate gene expression, such as recombinant expression, RNA interference and gene ablation (Wippersteg et al., 2002; Correnti et al., 2005; Brindley, 2005; Grevelding, 2006; Kines et al., 2006). However, the above mentioned experimental limitations seriously hamper the application of these genetic manipulation techniques in schistosomes and it has not been possible to produce stable transfected mutants producing transgenic offspring yet.
Genetic manipulation of schistosomes
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2006, LancetCitation Excerpt :A definitive solution to the schistosomiasis problem, finally, can be achieved only by eliminating its main underlying cause—poverty. The literature research for this Seminar started from standard works and recent reviews.1–10 We also used our own collections and the library holdings of the Antwerp Institute of Tropical Medicine, and searched PubMed and MEDLINE over the past 10 years for the main topics of this paper with the key words “schistosomes OR schistosomiasis OR schistosoma” PLUS “epidemiology”, “transmission”, “pathology”, “morbidity”, “mortality”, “immunology”, “vaccine”, “treatment”, “praziquantel”, “diagnosis”, “control”, “disease burden”, and “genital”.
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2006, Molecular and Biochemical Parasitology