The Schistosoma japonicum genome reveals features of host–parasite interplay (original) (raw)
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PLoS Pathogens, 2006
Schistosomiasis remains a serious public health problem with an estimated 200 million people infected in 76 countries. Here we isolated ; 8,400 potential protein-encoding cDNA contigs from Schistosoma japonicum after sequencing circa 84,000 expressed sequence tags. In tandem, we undertook a high-throughput proteomics approach to characterize the protein expression profiles of a number of developmental stages (cercariae, hepatic schistosomula, female and male adults, eggs, and miracidia) and tissues at the host-parasite interface (eggshell and tegument) by interrogating the protein database deduced from the contigs. Comparative analysis of these transcriptomic and proteomic data, the latter including 3,260 proteins with putative identities, revealed differential expression of genes among the various developmental stages and sexes of S. japonicum and localization of putative secretory and membrane antigens, enzymes, and other gene products on the adult tegument and eggshell, many of which displayed genetic polymorphisms. Numerous S. japonicum genes exhibited high levels of identity with those of their mammalian hosts, whereas many others appeared to be conserved only across the genus Schistosoma or Phylum Platyhelminthes. These findings are expected to provide new insights into the pathophysiology of schistosomiasis and for the development of improved interventions for disease control and will facilitate a more fundamental understanding of schistosome biology, evolution, and the host-parasite interplay. SJ, et al. (2006) New perspectives on host-parasite interplay by comparative transcriptomic and proteomic analyses of Schistosoma japonicum. PLoS Pathog 2(4): e29.
…, 2007
The tegument proteins of schistosome have attracted the most attention in studies of hostparasite interplay, while the host proteins acting at the host-parasite interface remained largely elusive. Here, we undertook a high-throughput proteomic approach to characterize the schistosome-adsorbed host proteins. Fifty five distinct host proteins were confidently identified in S. japonicum samples, including cercaria, schistosomula, adults, eggs, and miracidia, together with tegument and eggshell preparations, of which 23 and 38 host proteins were identified in adult worms and eggs, respectively. Among the schistosome-adsorbed host proteins, host neutrophil elastases were found in the granuloma initiated by schistosome egg deposition, implying that the host innate immune molecules could participate in the granuloma formation for fighting against schistosome invasion, except for the adaptive immune system. In addition, some host proteins, such as proteinase inhibitor and superoxide dismutase, might be utilized by schistosome to counteract or attenuate the host attacks. These parasite-adsorbed host proteins will provide new insights into the host immune responses against schistosome infection, the evasive behavior of the adult worms, and the granuloma formation, which could render an in-depth understanding for the host-parasite interplay.
Trends in Parasitology, 2011
Schistosoma genomes provide a comprehensive resource for identifying the molecular processes that shape parasite evolution and for discovering novel chemotherapeutic or immunoprophylactic targets. Here, we demonstrate how intra-and intergenus comparative genomics can be used to drive these investigations forward, illustrate the advantages and limitations of these approaches and review how post genomic technologies offer complementary strategies for genome characterisation. While sequencing and functional characterisation of other schistosome/ platyhelminth genomes continues to expedite anthelmintic discovery, we contend that future priorities should equally focus on improving assembly quality, and chromosomal assignment, of existing schistosome/platyhelminth genomes. Comparative genome basics July 2009 marked a seminal date in the history of parasite genomics, helminthology and evolutionary biology. After more than 20 years of collaborative research, both Schistosoma japonicum[1] and Schistosoma mansoni[2] draft genomes were elucidated using wholegenome shotgun sequencing (Glossary). Along with Schistosoma haematobium, these parasitic trematodes are responsible for most cases of human hepatosplenic (S. japonicum and S. mansoni) and urinary (S. haematobium) schistosomiasis[3], a chronic and morbid neglected tropical disease afflicting hundreds of millions of people in sub-Saharan Africa, Asia and South America[4]. Information contained in these genomes has fuelled optimism
Evolutionary and biomedical implications of a Schistosoma japonicum complementary DNA resource
Nature Genetics, 2003
Knowledge of the genome of this parasite should improve understanding of schistosome-host interactions, biomedical aspects of schistosomiasis and invertebrate evolution. We assigned 43,707 expressed sequence tags (ESTs) derived from adult S. japonicum and their eggs to 13,131 gene clusters. Of these, 35% shared no similarity with known genes and 75% had not been reported previously in schistosomes. Notably, S. japonicum encoded mammalian-like receptors for insulin, progesterone, cytokines and neuropeptides, suggesting that host hormones, or endogenous parasite homologs, could orchestrate schistosome development and maturation and that schistosomes modulate anti-parasite immune responses through inhibitors, molecular mimicry and other evasion strategies.
PLoS computational biology, 2014
Blood fluke proteases play pivotal roles in the processes of invasion, nutrition acquisition, immune evasion, and other host-parasite interactions. Hundreds of genes encoding putative proteases have been identified in the recently published schistosome genomes. However, the expression profiles of these proteases in Schistosoma species have not yet been systematically analyzed. We retrieved and culled the redundant protease sequences of Schistosoma japonicum, Schistosoma mansoni, Echinococcus multilocularis, and Clonorchis sinensis from public databases utilizing bioinformatic approaches. The degradomes of the four parasitic organisms and Homo sapiens were then comparatively analyzed. A total of 262 S. japonicum protease sequences were obtained and the expression profiles generated using whole-genome microarray. Four main clusters of protease genes with different expression patterns were identified: proteases up-regulated in hepatic schistosomula and adult worms, egg-specific or pred...
Transcriptome analysis of the acoelomate human parasite Schistosoma mansoni
Nature Genetics, 2003
We generated 163,000 expressed-sequence tags (ESTs) from normalized cDNA libraries from six selected developmental stages of the parasite, resulting in 31,000 assembled sequences and 92% sampling of an estimated 14,000 gene complement. By analyzing automated Gene Ontology assignments, we provide a detailed view of important S. mansoni biological systems, including characterization of metazoa-specific and eukarya-conserved genes. Phylogenetic analysis suggests an early divergence from other metazoa. The data set provides insights into the molecular mechanisms of tissue organization, development, signaling, sexual dimorphism, host interactions and immune evasion and identifies novel proteins to be investigated as vaccine candidates and potential drug targets.
A quantitative view of the transcriptome of Schistosoma mansoni adult-worms using SAGE
BMC Genomics, 2007
Background Five species of the genus Schistosoma, a parasitic trematode flatworm, are causative agents of Schistosomiasis, a disease that is endemic in a large number of developing countries, affecting millions of patients around the world. By using SAGE (Serial Analysis of Gene Expression) we describe here the first large-scale quantitative analysis of the Schistosoma mansoni transcriptome, one of the most epidemiologically relevant species of this genus. Results After extracting mRNA from pooled male and female adult-worms, a SAGE library was constructed and sequenced, generating 68,238 tags that covered more than 6,000 genes expressed in this developmental stage. An analysis of the ordered tag-list shows the genes of F10 eggshell protein, pol-polyprotein, HSP86, 14-3-3 and a transcript yet to be identified to be the five top most abundant genes in pooled adult worms. Whereas only 8% of the 100 most abundant tags found in adult worms of S. mansoni could not be assigned to transcri...
Developmental gene expression profiles of the human pathogen Schistosoma japonicum
BMC Genomics, 2009
Background: The schistosome blood flukes are complex trematodes and cause a chronic parasitic disease of significant public health importance worldwide, schistosomiasis. Their life cycle is characterised by distinct parasitic and free-living phases involving mammalian and snail hosts and freshwater. Microarray analysis was used to profile developmental gene expression in the Asian species, Schistosoma japonicum. Total RNAs were isolated from the three distinct environmental phases of the lifecycle-aquatic/snail (eggs, miracidia, sporocysts, cercariae), juvenile (lung schistosomula and paired but pre-egg laying adults) and adult (paired, mature males and eggproducing females, both examined separately). Advanced analyses including ANOVA, principal component analysis, and hierarchal clustering provided a global synopsis of gene expression relationships among the different developmental stages of the schistosome parasite. Results: Gene expression profiles were linked to the major environmental settings through which the developmental stages of the fluke have to adapt during the course of its life cycle. Gene ontologies of the differentially expressed genes revealed a wide range of functions and processes. In addition, stage-specific, differentially expressed genes were identified that were involved in numerous biological pathways and functions including calcium signalling, sphingolipid metabolism and parasite defence. Conclusion: The findings provide a comprehensive database of gene expression in an important human pathogen, including transcriptional changes in genes involved in evasion of the host immune response, nutrient acquisition, energy production, calcium signalling, sphingolipid metabolism, egg production and tegumental function during development. This resource should help facilitate the identification and prioritization of new anti-schistosome drug and vaccine targets for the control of schistosomiasis.
Schistosome genomes: a wealth of information
Trends in Parasitology, 2010
The blood flukes Schistosoma japonicum and Schistosoma mansoni are the first major human platyhelminth pathogens to have their genome sequences published. The work of two large international consortia offers draft sequence information and detailed analyses presenting a wealth of information addressing, in particular, metabolic and signalling pathways, hostparasite interactions and potential new drug targets. We comment on these breakthroughs and their potential applications in the study and control of schistosomes.