Cestode genomics - progress and prospects for advancing basic and applied aspects of flatworm biology

Department of Zoology, The Natural History Museum, London, UK.
Parasite Immunology (Impact Factor: 1.85). 07/2012; 34(2-3):130-50. DOI: 10.1111/j.1365-3024.2011.01319.x
Source: PubMed

ABSTRACT Characterization of the first tapeworm genome, Echinococcus multilocularis, is now nearly complete, and genome assemblies of E. granulosus, Taenia solium and Hymenolepis microstoma are in advanced draft versions. These initiatives herald the beginning of a genomic era in cestodology and underpin a diverse set of research agendas targeting both basic and applied aspects of tapeworm biology. We discuss the progress in the genomics of these species, provide insights into the presence and composition of immunologically relevant gene families, including the antigen B- and EG95/45W families, and discuss chemogenomic approaches toward the development of novel chemotherapeutics against cestode diseases. In addition, we discuss the evolution of tapeworm parasites and introduce the research programmes linked to genome initiatives that are aimed at understanding signalling systems involved in basic host-parasite interactions and morphogenesis.

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Available from: Klaus Brehm, Aug 31, 2015
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    • "have contributed to some of the important differences in larval morphology and development found between these closely related species (Thompson 1986). These differences have long been considered puzzling, particularly since the gene complement of both species is almost identical and no notable differences in genome organization had been identified between them so far (Olson et al. 2012; Tsai et al. 2013). The genes showing transcriptional fusions to upstream solo-LTRs have a variety of roles in important biological pathways. "
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    ABSTRACT: Taeniid cestodes (including the human parasites Echinococcus spp. and Taenia solium) have very few mobile genetic elements (MGEs) in their genome, despite lacking a canonical PIWI pathway. The MGEs of these parasites are virtually unexplored, and nothing is known about their expression and silencing. In this work, we report the discovery of a novel family of small non-autonomous Long Terminal Repeat retrotransposons (also known as Terminal Repeat Retrotransposons in Miniature, TRIMs) which we have named ta-TRIM (taeniid TRIM). ta-TRIMs are only the second family of TRIM elements discovered in animals, and are likely the result of convergent reductive evolution in different taxonomic groups. These elements originated at the base of the taeniid tree and have expanded during taeniid diversification, including after the divergence of closely related species such as E. multilocularis and E. granulosus. They are massively expressed in larval stages, from a small proportion of full-length copies and from isolated terminal repeats that show transcriptional read-through into downstream regions, generating novel non-coding RNAs and transcriptional fusions to coding genes. In E. multilocularis, ta-TRIMs are specifically expressed in the germinative cells (the somatic stem cells) during asexual reproduction of metacestode larvae. This would provide a developmental mechanism for insertion of ta-TRIMs into cells that will eventually generate the adult germ line. Future studies of active and inactive ta-TRIM elements could give the first clues on MGE silencing mechanisms in cestodes. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
    Genome Biology and Evolution 07/2015; 7(8):2136. DOI:10.1093/gbe/evv126 · 4.53 Impact Factor
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    • "To date, discussions of the emergence of platyhelminth parasitism have focused on organismic and morphological traits—in other words, those character systems for which data have been historically available. However, principally because of their importance as human pathogens, genomic data are now available from all major lineages of Neodermata, including well-curated assemblies, annotation efforts, and experimental protocols for species such as Echinococcus multilocularis (Brehm, 2010; Olson et al., 2012; Tsai et al., 2013) and Schistosoma mansoni (Collins et al., 2013; Wang et al., 2013). With such data available, there has been much discussion of the genome-level adaptations to parasitism, with suggestions of many apparent losses, including several homeobox genes, vasa, tudor, and piwi orthologs, fatty and amino acid biosynthesis pathways, and peroxisome components; proposed gains include the evolution of a neodermatan-specific Argonaute subfamily and micro-exon gene organization (Tsai et al., 2013; Hahn et al., 2014). "
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    ABSTRACT: Flatworms number among the most diverse invertebrate phyla, and represent the most biomedically significant branch of the major bilaterian clade Spiralia, but to date, deep evolutionary relationships within this group have been studied using only a single locus (the rRNA operon), leaving the origins of many key clades unclear. Here, using a survey of genomes and transcriptomes representing all free-living flatworm orders, we provide resolution of platyhelminth interrelationships based on hundreds of nuclear protein-coding genes, exploring phylogenetic signal through concatenation as well as recently developed consensus approaches. These analyses robustly support a modern hypothesis of flatworm phylogeny, one which emphasizes the primacy of the often-overlooked 'microturbellarian' groups in understanding the major evolutionary transitions within Platyhelminthes: perhaps most notably, we propose a novel scenario for the interrelationships between free-living and vertebrate-parasitic flatworms, providing new opportunities to shed light on the origins and biological consequences of parasitism in these iconic invertebrates.
    eLife Sciences 03/2015; 4. DOI:10.7554/eLife.05503 · 8.52 Impact Factor
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    • "During recent years, we have developed several cultivation systems by which the developmental transitions of E. multilocularis larvae within the intermediate host can be mimicked in vitro[2,17-19]. These include systems for investigating proliferation and differentiation of metacestode vesicles under host cell free conditions [18] as well as a parasite stem cell cultivation system that closely mimics the metamorphic transition of the oncosphere towards the metacestode [19,20]. Using these systems we addressed, in the present study, questions on the influence of physiological concentrations of human insulin on parasite development, glucose uptake and the activation of Echinococcus insulin signalling pathways. "
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    ABSTRACT: The metacestode of the tapeworm Echinococcus multilocularis is the causative agent of alveolar echinococcosis, a lethal zoonosis. Infections are initiated through establishment of parasite larvae within the intermediate host's liver, where high concentrations of insulin are present, followed by tumour-like growth of the metacestode in host organs. The molecular mechanisms determining the organ tropism of E. multilocularis or influences of host hormones on parasite proliferation are poorly understood to date. Using in vitro cultivation systems for parasite larvae we show that physiological concentrations (10 nM) of human insulin significantly stimulate the formation of metacestode larvae from parasite stem cells and promote asexual growth of the metacestode. Addition of human insulin to parasite larvae led to increased glucose uptake and enhanced phosphorylation of Echinococcus insulin signalling components, including an insulin receptor-like kinase, EmIR1, for which we demonstrate predominant expression in the parasite's glycogen storage cells. We also characterized a second insulin receptor family member, EmIR2, and demonstrated interaction of its ligand binding domain with human insulin in the yeast two-hybrid system. Addition of an insulin receptor inhibitor resulted in metacestode killing, prevented metacestode development from parasite stem cells, and impaired the activation of insulin signalling pathways through host insulin. Our data indicate that host insulin acts as a stimulant for parasite development within the host liver and that E. multilocularis senses the host hormone through an evolutionarily conserved insulin signalling pathway. Hormonal host-parasite cross-communication, facilitated by the relatively close phylogenetic relationship between E. multilocularis and its mammalian hosts, thus appears to be important in the pathology of alveolar echinococcosis. This contributes to a closer understanding of organ tropism and parasite persistence in larval cestode infections. Furthermore, our data show that Echinococcus insulin signalling pathways are promising targets for the development of novel drugs.
    BMC Biology 01/2014; 12(1):5. DOI:10.1186/1741-7007-12-5 · 7.98 Impact Factor
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