Frontiers of Medicine in China

, Volume 4, Issue 2, pp 157–165

Systems biomedical analysis of Schistosoma japonicum



Human schistosomiasis, caused mainly by three principal species including Schistosoma japonicum, S. mansoni, and S. hematobium, remains a major public health concern worldwide. S. japonicum is prevalent in southern China, being a major disease risk for 66 million people. The blood fluke has a complex life cycle for survival: as a free-living form in fresh water and as a parasite in the snail intermediate and vertebrate definitive hosts. Systems-based biomedical analyses, including genomic, transcriptomic, proteomic and metabonomic approaches, have been performed on the schistosome. These comprehensive investigations have not only characterized the genomic features but also chartered gene and protein expression profiles across genders and developmental stages. The integration of the huge information will lay a global and solid foundation for the molecular architecture of the biology, pathogenesis, and host-parasite interactions of the human blood fluke, which will facilitate the development of a new antischistosomal vaccine and drugs as well as diagnostic markers for the treatment and control of schistosomiasis.


Schistosoma japonicum systems biomedical analysis 


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  1. 1.
    Engels D, Chitsulo L, Montresor A, Savioli L. The global epidemiological situation of schistosomiasis and new approaches to control and research. Acta Trop, 2002, 82(2): 139–146CrossRefPubMedGoogle Scholar
  2. 2.
    Gryseels B, Polman K, Clerinx J, Kestens L. Human schistosomiasis. Lancet, 2006, 368(9541): 1106–1118CrossRefPubMedGoogle Scholar
  3. 3.
    Haas W, Diekhoff D, Koch K, Schmalfuss G, Loy C. Schistosoma mansoni cercariae: stimulation of acetabular gland secretion is adapted to the chemical composition of mammalian skin. J Parasitol, 1997, 83(6): 1079–1085CrossRefPubMedGoogle Scholar
  4. 4.
    Haas W, Schmitt R. Characterization of chemical stimuli for the penetration of Schistosoma mansoni cercariae. I. Effective substances, host specificity. Z Parasitenkd, 1982, 66(3): 293–307CrossRefPubMedGoogle Scholar
  5. 5.
    Abath F G C, Morais C N L, Montenegro C E L, Wynn T A, Montenegro S M L. Immunopathogenic mechanisms in schistosomiasis: What can be learnt from human studies? Trends Parasitol, 2006, 22(2): 85–91CrossRefPubMedGoogle Scholar
  6. 6.
    Amiri P, Locksley R M, Parslow T G, Sadick M, Rector E, Ritter D, McKerrow J H. Tumor necrosis factor alpha restores granulomas and induces parasite egg-laying in schistosome-infected SCID mice. Nature, 1992, 356(6370): 604–607CrossRefPubMedGoogle Scholar
  7. 7.
    Davies S J, Grogan J L, Blank R B, Lim K C, Locksley R M, McKerrow J H. Modulation of blood fluke development in the liver by hepatic CD4+ lymphocytes. Science, 2001, 294(5545): 1358–1361CrossRefPubMedGoogle Scholar
  8. 8.
    de Mendonça R L, Escrivá H, Bouton D, Laudet V, Pierce R J. Hormones and nuclear receptors in schistosome development. Parasitol Today, 2000, 16(6): 233–240CrossRefPubMedGoogle Scholar
  9. 9.
    Ravindran B. Are inflammation and immunological hyperactivity needed for filarial parasite development? Trends Parasitol, 2001, 17(2): 70–73CrossRefPubMedGoogle Scholar
  10. 10.
    Escobedo G, Roberts C W, Carrero J C, Morales-Montor J. Parasite regulation by host hormones: an old mechanism of host exploitation? Trends Parasitol, 2005, 21(12): 588–593CrossRefPubMedGoogle Scholar
  11. 11.
    Schistosoma japonicum Genome Sequencing and Functional Analysis Consortium. The Schistosoma japonicum genome reveals features of host-parasite interplay. Nature, 2009, 460(7253): 345–351Google Scholar
  12. 12.
    Hu W, Yan Q, Shen D K, Liu F, Zhu Z D, Song H D, Xu X R, Wang Z J, Rong Y P, Zeng L C, Wu J, Zhang X, Wang J J, Xu X N, Wang S Y, Fu G, Zhang X L, Wang Z Q, Brindley P J, McManus D P, Xue C L, Feng Z, Chen Z, Han Z G. Evolutionary and biomedical implications of a Schistosoma japonicum complementary DNA resource. Nat Genet, 2003, 35(2): 139–147CrossRefPubMedGoogle Scholar
  13. 13.
    Liu F, Lu J, Hu W, Wang S Y, Cui S J, Chi M, Yan Q, Wang X R, Song H D, Xu X N, Wang J J, Zhang X L, Zhang X, Wang Z Q, Xue C L, Brindley P J, McManus D P, Yang P Y, Feng Z, Chen Z, Han Z G. New perspectives on host-parasite interplay by comparative transcriptomic and proteomic analyses of Schistosoma japonicum. PLoS Pathog, 2006, 2(4): e29CrossRefPubMedGoogle Scholar
  14. 14.
    Liu F, Hu W, Cui S J, Chi M, Fang C Y, Wang Z Q, Yang P Y, Han Z G. Insight into the host-parasite interplay by proteomic study of host proteins copurified with the human parasite, Schistosoma japonicum. Proteomics, 2007, 7(3): 450–462CrossRefPubMedGoogle Scholar
  15. 15.
    Liu F, Cui S J, Hu W, Feng Z, Wang Z Q, Han Z G. Excretory/secretory proteome of the adult developmental stage of human blood fluke, Schistosoma japonicum. Mol Cell Proteomics, 2009, 8(6): 1236–1251CrossRefPubMedGoogle Scholar
  16. 16.
    Huang J, Hao P, Chen H, Hu W, Yan Q, Liu F, Han Z G. Genome-wide identification of Schistosoma japonicum microRNAs using a deep-sequencing approach. PLoS One, 2009, 4(12): e8206CrossRefPubMedGoogle Scholar
  17. 17.
    Berriman M, Haas B J, LoVerde P T, Wilson R A, Dillon G P, Cerqueira G C, Mashiyama S T, Al-Lazikani B, Andrade L F, Ashton P D, Aslett M A, Bartholomeu D C, Blandin G, Caffrey C R, Coghlan A, Coulson R, Day T A, Delcher A, DeMarco R, Djikeng A, Eyre T, Gamble J A, Ghedin E, Gu Y, Hertz-Fowler C, Hirai H, Hirai Y, Houston R, Ivens A, Johnston D A, Lacerda D, Macedo C D, McVeigh P, Ning Z, Oliveira G, Overington J P, Parkhill J, Pertea M, Pierce R J, Protasio A V, Quail M A, Rajandream M A, Rogers J, Sajid M, Salzberg S L, Stanke M, Tivey A R, White O, Williams D L, Wortman J, Wu W, Zamanian M, Zerlotini A, Fraser-Liggett C M, Barrell B G, El-Sayed N M. The genome of the blood fluke Schistosoma mansoni. Nature, 2009, 460(7253): 352–358CrossRefPubMedGoogle Scholar
  18. 18.
    Verjovski-Almeida S, DeMarco R, Martins E A, Guimarães P E, Ojopi E P, Paquola A C, Piazza J P, Nishiyama M Y Jr, Kitajima J P, Adamson R E, Ashton P D, Bonaldo M F, Coulson P S, Dillon G P, Farias L P, Gregorio S P, Ho P L, Leite R A, Malaquias L C, Marques R C, Miyasato P A, Nascimento A L, Ohlweiler F P, Reis E M, Ribeiro M A, Sá R G, Stukart G C, Soares M B, Gargioni C, Kawano T, Rodrigues V, Madeira A M, Wilson R A, Menck C F, Setubal J C, Leite L C, Dias-Neto E. Transcriptome analysis of the acoelomate human parasite Schistosoma mansoni. Nat Genet, 2003, 35(2): 148–157CrossRefPubMedGoogle Scholar
  19. 19.
    Han Z G, Brindley P J, Wang S Y, Chen Z. Schistosoma genomics: new perspectives on schistosome biology and host-parasite interaction. Annu Rev Genomics Hum Genet, 2009, 10: 211–240CrossRefPubMedGoogle Scholar
  20. 20.
    Brindley P J, Mitreva M, Ghedin E, Lustigman S. Helminth genomics: The implications for human health. PLoS Negl Trop Dis, 2009, 3(10): e538CrossRefPubMedGoogle Scholar
  21. 21.
    Hu W, Brindley P J, McManus D P, Feng Z, Han Z G. Schistosome transcriptomes: new insights into the parasite and schistosomiasis. Trends Mol Med, 2004, 10(5): 217–225CrossRefPubMedGoogle Scholar
  22. 22.
    Simpson A J, Sher A, McCutchan T F. The genome of Schistosoma mansoni: isolation of DNA, its size, bases and repetitive sequences. Mol Biochem Parasitol, 1982, 6(2): 125–137CrossRefPubMedGoogle Scholar
  23. 23.
    Johnston D A, Blaxter M L, Degrave W M, Foster J, Ivens A C, Melville S E. Genomics and the biology of parasites. Bioessays, 1999, 21(2): 131–147CrossRefPubMedGoogle Scholar
  24. 24.
    Franco G R, Valadão A F, Azevedo V, Rabelo E M. The Schistosoma gene discovery program: state of the art. Int J Parasitol, 2000, 30(4): 453–463CrossRefPubMedGoogle Scholar
  25. 25.
    Shrivastava J, Qian B Z, Mcvean G, Webster J P. An insight into the genetic variation of Schistosoma japonicum in mainland China using DNA microsatellite markers. Mol Ecol, 2005, 14(3): 839–849CrossRefPubMedGoogle Scholar
  26. 26.
    Hokke C H, Fitzpatrick J M, Hoffmann K F. Integrating transcriptome, proteome and glycome analyses of Schistosoma biology. Trends Parasitol, 2007, 23(4): 165–174CrossRefPubMedGoogle Scholar
  27. 27.
    van Hellemond J J, van Balkom B W, Tielens A G. Schistosome biology and proteomics: progress and challenges. Exp Parasitol, 2007, 117(3): 267–274CrossRefPubMedGoogle Scholar
  28. 28.
    Wilson R A, Ashton P D, Braschi S, Dillon G P, Berriman M, Ivens A. ’Oming in on schistosomes: prospects and limitations for post-genomics. Trends Parasitol, 2007, 23(1): 14–20CrossRefPubMedGoogle Scholar
  29. 29.
    Cheng G F, Lin J J, Feng X G, Fu Z Q, Jin Y M, Yuan C X, Zhou Y C, Cai Y M. Proteomic analysis of differentially expressed proteins between the male and female worm of Schistosoma japonicum after pairing. Proteomics, 2005, 5(2): 511–521CrossRefPubMedGoogle Scholar
  30. 30.
    McLaren D J, Hockley D J. Blood flukes have a double outer membrane. Nature, 1977, 269(5624): 147–149CrossRefPubMedGoogle Scholar
  31. 31.
    Jenkins S J, Hewitson J P, Jenkins G R, Mountford A P. Modulation of the host’s immune response by schistosome larvae. Parasite Immunol, 2005, 27(10–11): 385–393CrossRefPubMedGoogle Scholar
  32. 32.
    Lightowlers M W, Rickard M D. Excretory-secretory products of helminth parasites: effects on host immune responses. Parasitology, 1988, 96(Suppl): S123–166PubMedGoogle Scholar
  33. 33.
    Nicholson J K, Lindon J C. Systems biology — metabonomics. Nature, 2008, 455(7216): 1054–1056CrossRefPubMedGoogle Scholar
  34. 34.
    Wang Y, Holmes E, Nicholson J K, Cloarec O, Chollet J, Tanner M, Singer B H, Utzinger J. Metabonomic investigations in mice infected with Schistosoma mansoni: an approach for biomarker identification. Proc Natl Acad Sci USA, 2004, 101(34): 12676–12681CrossRefPubMedGoogle Scholar
  35. 35.
    Wang Y, Utzinger J, Xiao S H, Xue J, Nicholson J K, Tanner M, Singer B H, Holmes E. System level metabolic effects of a Schistosoma japonicum infection in the Syrian hamster. Mol Biochem Parasitol, 2006, 146(1): 1–9CrossRefPubMedGoogle Scholar
  36. 36.
    Wu J F, Holmes E, Xue J, Xiao S H, Singer B H, Tang H R, Utzinger J, Wang Y L. Metabolic alterations in the hamster co-infected with Schistosoma japonicum and Necator americanus. Int J Parasitol, 2010, 40(6): 695–703CrossRefPubMedGoogle Scholar
  37. 37.
    Skelly P J, Kim J W, Cunningham J, Shoemaker C B. Cloning, characterization, and functional expression of cDNAs encoding glucose transporter proteins from the human parasite Schistosoma mansoni. J Biol Chem, 1994, 269(6): 4247–4253PubMedGoogle Scholar
  38. 38.
    Skelly P J, Shoemaker C B. Rapid appearance and asymmetric distribution of glucose transporter SGTP4 at the apical surface of intramammalian-stage Schistosoma mansoni. Proc Natl Acad Sci U S A, 1996, 93(8): 3642–3646CrossRefPubMedGoogle Scholar
  39. 39.
    Cohen L M, Neimark H, Eveland L K. Schistosoma mansoni: response of cercariae to a thermal gradient. J Parasitol, 1980, 66(2): 362–364CrossRefPubMedGoogle Scholar
  40. 40.
    Maizels R M, Bundy D A, Selkirk M E, Smith D F, Anderson R M. Immunological modulation and evasion by helminth parasites in human populations. Nature, 1993, 365(6449): 797–805CrossRefPubMedGoogle Scholar
  41. 41.
    McKerrow J H. Cytokine induction and exploitation in schistosome infections. Parasitology, 1997, 115(Suppl): 107–112CrossRefGoogle Scholar
  42. 42.
    Dvorák J, Mashiyama S T, Braschi S, Sajid M, Knudsen G M, Hansell E, Lim K C, Hsieh I, Bahgat M, Mackenzie B, Medzihradszky K F, Babbitt P C, Caffrey C R, McKerrow J H. Differential use of protease families for invasion by schistosome cercariae. Biochimie, 2008, 90(2): 345–358CrossRefPubMedGoogle Scholar
  43. 43.
    Koehler J W, Morales M E, Shelby B D, Brindley P J. Aspartic protease activities of schistosomes cleave mammalian hemoglobins in a host-specific manner. Mem Inst Oswaldo Cruz, 2007, 102(1): 83–85CrossRefPubMedGoogle Scholar
  44. 44.
    Zhou X N, Wang L Y, Chen M G, Wu X H, Jiang Q W, Chen X Y, Zheng J, Utzinger J. The public health significance and control of schistosomiasis in China- then and now. Acta Trop, 2005, 96(2–3): 97–105CrossRefPubMedGoogle Scholar
  45. 45.
    Utzinger J, Zhou X N, Chen M G, Bergquist R. Conquering schistosomiasis in China: the long march. Acta Trop, 2005, 96(2–3): 69–96PubMedGoogle Scholar
  46. 46.
    Li Y S, Raso G, Zhao Z Y, He Y K, Ellis M K, McManus D P. Large water management projects and schistosomiasis control, Dongting Lake region, China. Emerg Infect Dis, 2007, 13(7): 973–979PubMedGoogle Scholar
  47. 47.
    Bergquist R, Utzinger J, McManus D P. Trick or treat: the role of vaccines in integrated schistosomiasis control. PLoS Negl Trop Dis, 2008, 2(6): e244CrossRefPubMedGoogle Scholar
  48. 48.
    Ismail M, Botros S, Metwally A, William S, Farghally A, Tao L F, Day T A, Bennett J L. Resistance to praziquantel: direct evidence from Schistosoma mansoni isolated from Egyptian villagers. Am J Trop Med Hyg, 1999, 60(6): 932–935PubMedGoogle Scholar
  49. 49.
    Stelma F F, Talla I, Sow S, Kongs A, Niang M, Polman K, Deelder A M, Gryseels B. Efficacy and side effects of praziquantel in an epidemic focus of Schistosoma mansoni. Am J Trop Med Hyg, 1995, 53(2): 167–170PubMedGoogle Scholar
  50. 50.
    Doenhoff M J, Cioli D, Utzinger J. Praziquantel: mechanisms of action, resistance and new derivatives for schistosomiasis. Curr Opin Infect Dis, 2008, 21(6): 659–667CrossRefPubMedGoogle Scholar
  51. 51.
    Gourlay L J, Angelucci F, Baiocco P, Boumis G, Brunori M, Bellelli A, Miele A E. The three-dimensional structure of two redox states of cyclophilin A from Schistosoma mansoni. Evidence for redox regulation of peptidyl-prolyl cis-trans isomerase activity. J Biol Chem, 2007, 282(34): 24851–24857CrossRefPubMedGoogle Scholar
  52. 52.
    Sayed A A, Simeonov A, Thomas C J, Inglese J, Austin C P, Williams D L. Identification of oxadiazoles as new drug leads for the control of schistosomiasis. Nat Med, 2008, 14(4): 407–412CrossRefPubMedGoogle Scholar
  53. 53.
    Kuntz A N, Davioud-Charvet E, Sayed A A, Califf L L, Dessolin J, Arnér E S, Williams D L. Thioredoxin glutathione reductase from Schistosoma mansoni: an essential parasite enzyme and a key drug target. PLoS Med, 2007, 4(6): e206CrossRefPubMedGoogle Scholar
  54. 54.
    Wu W, Niles E G, Hirai H, LoVerde P T. Evolution of a novel subfamily of nuclear receptors with members that each contain two DNA binding domains. BMC Evol Biol, 2007, 7: 27CrossRefPubMedGoogle Scholar
  55. 55.
    Freitas T C, Jung E, Pearce E J. TGF-beta signaling controls embryo development in the parasitic flatworm Schistosoma mansoni. PLoS Pathog, 2007, 3(4): e52CrossRefPubMedGoogle Scholar
  56. 56.
    Osman A, Niles E G, Verjovski-Almeida S, LoVerde P T. Schistosoma mansoni TGF-beta receptor II: role in host ligandinduced regulation of a schistosome target gene. PLoS Pathog, 2006, 2(6): e54CrossRefPubMedGoogle Scholar
  57. 57.
    Morales M E, Rinaldi G, Gobert G N, Kines K J, Tort J F, Brindley P J. RNA interference of Schistosoma mansoni cathepsin D, the apical enzyme of the hemoglobin proteolysis cascade. Mol Biochem Parasitol, 2008, 157(2): 160–168CrossRefPubMedGoogle Scholar
  58. 58.
    Correnti J M, Brindley P J, Pearce E J. Long-term suppression of cathepsin B levels by RNA interference retards schistosome growth. Mol Biochem Parasitol, 2005, 143(2): 209–215CrossRefPubMedGoogle Scholar
  59. 59.
    McManus D P, Loukas A. The current status of vaccines for schistosomiasis. Clin Microbiol Rev, 2008, 21(1): 225–242CrossRefPubMedGoogle Scholar
  60. 60.
    Loukas A, Tran M, Pearson M S. Schistosome membrane proteins as vaccines. Int J Parasitol, 2007, 37(3–4): 257–263CrossRefPubMedGoogle Scholar
  61. 61.
    Tran M H, Pearson M S, Bethony J M, Smyth D J, Jones M K, Duke M, Don T A, McManus D P, Correa-Oliveira R, Loukas A. Tetraspanins on the surface of Schistosoma mansoni are protective antigens against schistosomiasis. Nat Med, 2006, 12(7): 835–840CrossRefPubMedGoogle Scholar
  62. 62.
    Hotez P J, Molyneux D H, Fenwick A, Kumaresan J, Sachs S E, Sachs J D, Savioli L. Control of neglected tropical diseases. N Engl J Med, 2007, 357(10): 1018–1027CrossRefPubMedGoogle Scholar
  63. 63.
    Wang L D, Chen H G, Guo J G, Zeng X J, Hong X L, Xiong J J, Wu X H, Wang X H, Wang L Y, Xia G, Hao Y, Chin D P, Zhou X N. A strategy to control transmission of Schistosoma japonicum in China. N Engl J Med, 2009, 360(2): 121–128CrossRefPubMedGoogle Scholar
  64. 64.
    Bergquist R, Johansen M V, Utzinger J. Diagnostic dilemmas in helminthology: what tools to use and when? Trends Parasitol, 2009, 25(4): 151–156CrossRefPubMedGoogle Scholar

Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  1. 1.Shanghai-MOST Key Laboratory for Disease and Health GenomicsChinese National Human Genome Center at ShanghaiShanghaiChina
  2. 2.Rui-Jin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

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