New Perspectives on Host-Parasite Interplay by Comparative Transcriptomic and Proteomic Analyses of Schistosoma japonicum

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Abstract
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. Schistosomiasis remains a major public health problem in the developing world. Schistosoma japonicum, the Oriental blood fluke, causes intestinal schistosomiasis in China and the Philippines. Knowledge of the genome and proteome of this worm should improve understanding of biomedical aspects of schistosomiasis. This study represents the first major attempt to characterize the majority of the expressed genes and proteins of a human blood fluke through rigorous, high-throughput genomic and proteomic methodologies. The findings of this study provide a unique resource of numerous schistosome genes and information on protein profiles of the different developmental stages of S. japonicum. Many of the newly discovered proteins are localized on the surface of the worm and its eggs, and they are likely to be involved in the pathogenesis of schistosomiasis. Furthermore, genetic variants found in many of these new genes likely reflect the ability of this important human pathogen to adapt and respond to environmental pressures and the capacity of the parasite to respond to anti-schistosomal therapies. Comparison of these S. japonicum genes with those from mammals and other organisms will facilitate advances in the understanding of blood fluke biology and evolution.