Role of the gp85/Trans-Sialidase Superfamily of Glycoproteins in the Interaction of Trypanosoma cruzi with Host Structures

Part of the Subcellular Biochemistry book series (SCBI, volume 47)


Invasion of mammalian cells by T. cruzi trypomastigotes is a multi-step and complex process involving several adhesion molecules, signaling events and proteolytic activities. From the blood to the cell target in different tissues the parasite has to interact with different cells and the extracellular matrix (ECM). The review focus on the role of the gp85/trans-sialidase superfamily members in the interaction of the parasite with the host cell, particularly with ECM components, with emphasis on the significant variability among the ligands and receptors involved. Use of the SELEX technique to evolve nuclease-resistant RNA aptamers for receptor identification is briefly discussed.


Sialic Acid Heparan Sulfate Trypanosoma Cruzi Host Structure Parasitophorous Vacuole 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Chagas C. Nova tripanosomiaze humana. Mem Inst Oswaldo Cruz 1909; I(II):159.Google Scholar
  2. 2.
    Hoare CA. The Trypanosomes of Mammals. Oxford: Blackwell Scientific Publications, 1972.Google Scholar
  3. 3.
    De Souza W. Basic cell biology of Trypanosoma cruzi. Curr Pharm Des 2002; 8(4):269–285.PubMedCrossRefGoogle Scholar
  4. 4.
    Almeida-de-Faria M, Freymuller E, Colli W et al. Trypanosoma cruzi: Characterization of an intracellular epimastigote-like form. Exp Parasitol 1999; 92(4):263–274.PubMedCrossRefGoogle Scholar
  5. 5.
    Tyler KM, Engman DM. The life cycle of Trypanosoma cruzi revisited. Int J Parasitol 2001; 31(5–6):472–481.PubMedCrossRefGoogle Scholar
  6. 6.
    Tonelli RR, Silber AM, Almeida-de-Faria M et al. L-proline is essential for the intracellular differentiation of Trypanosoma cruzi. Cell Microbiol 2004; 6(8):733–741.PubMedCrossRefGoogle Scholar
  7. 7.
    WHO. Technical Report Series: WHO Publications, 2002.Google Scholar
  8. 8.
    Williams-Blangero S, VandeBerg JL, Blangero J et al. Genetic epidemiology of Trypanosoma cruzi infection and Chagas’ disease. Front Biosci 2003; 8:e337–345.PubMedCrossRefGoogle Scholar
  9. 9.
    Buscaglia CA, Di Noia JM. Trypanosoma cruzi clonal diversity and the epidemiology of Chagas’ disease. Microbes Infect 2003; 5(5):419–427.PubMedCrossRefGoogle Scholar
  10. 10.
    Macedo AM, Machado CR, Oliveira RP et al. Trypanosoma cruzi: Genetic structure of populations and relevance of genetic variability to the pathogenesis of chagas disease. Mem Inst Oswaldo Cruz 2004; 99(1):1–12.PubMedCrossRefGoogle Scholar
  11. 11.
    Prata A. Clinical and epidemiological aspects of Chagas disease. Lancet Infect Dis 2001; 1:92–100.PubMedCrossRefGoogle Scholar
  12. 12.
    Mortara RA, Andreoli WK, Taniwaki NN et al. Mammalian cell invasion and intracellular trafficking by Trypanosoma cruzi infective forms. An Acad Bras Cienc 2005; 77(1):77–94.PubMedGoogle Scholar
  13. 13.
    Lima MT, Lenzi HL, Gattass CR. Negative tissue parasitism in mice injected with a noninfective clone of Trypanosoma cruzi. Parasitol Res 1995; 81(1):6–12.PubMedCrossRefGoogle Scholar
  14. 14.
    Lenzi HL, Oliveira DN, Lima MT et al. Trypanosoma cruzi: Paninfectivity of CL strain during murine acute infection. Exp Parasitol 1996; 84(1):16–27.PubMedCrossRefGoogle Scholar
  15. 15.
    Schenkman S, Mortara RA. HeLa cells extend and internalize pseudopodia during active invasion by Trypanosoma cruzi trypomastigotes. J Cell Sci 1992; 101 (Pt 4):895–905.PubMedGoogle Scholar
  16. 16.
    Freitas JM, Lages-Silva E, Crema E et al. Real time PCR strategy for the identification of major lineages of Trypanosoma cruzi directly in chronically infected human tissues. Int J Parasitol 2005; 35(4):411–417.PubMedCrossRefGoogle Scholar
  17. 17.
    Taliaferro H, Pizzi T. Connective tissue reaction in normal and immunized mice to a reticulotropic strains of Trypanosoma cruzi. J Infect Dis 1955; 96:199–226.PubMedGoogle Scholar
  18. 18.
    Bice D, Zeledon R. Comparison of infectivity of strains of Trypanosoma cruzi (Chagas 1909). J Parasitol 1970; 56:663–670.PubMedCrossRefGoogle Scholar
  19. 19.
    Melo RaB Z. Tissue tropism of different T. cruzi strains. J Parasitol 1978; 64:475–482.CrossRefGoogle Scholar
  20. 20.
    Schoemaker J, Hoffman JR, Hoffman DG. Trypanosoma cruzi: Preference for brown adipose tissue in mice by the Tulahuen strain. Exp Parasitol 1970; 27:403–407.CrossRefGoogle Scholar
  21. 21.
    Buckner FS, Wilson AJ, Van Voorhis WC. Detection of live Trypanosoma cruzi in tissues of infected mice by using histochemical stain for beta-galactosidase. Infect Immun 1999; 67(1):403–409.PubMedGoogle Scholar
  22. 22.
    Burleigh BA, Andrews NW. The mechanisms of Trypanosoma cruzi invasion of mammalian cells. Annu Rev Microbiol 1995; 49:175–200.PubMedCrossRefGoogle Scholar
  23. 23.
    Burleigh BA, Woolsey AM. Cell signalling and Trypanosoma cruzi invasion. Cell Microbiol 2002; 4(11):701–711.PubMedCrossRefGoogle Scholar
  24. 24.
    Yoshida N. Molecular basis of mammalian cell invasion by Trypanosoma cruzi. Anais da Academia Brasileira de Ciencias 2005; 77(3):1–25.Google Scholar
  25. 25.
    Barbosa HS, Meirelles MN. Evidence of participation of cytoskeleton of heart muscle cells during the invasion of Trypanosoma cruzi. Cell Struct Funct 1995; 20(4):275–284.PubMedCrossRefGoogle Scholar
  26. 26.
    Mortara RA. Trypanosoma cruzi: Amastigotes and trypomastigotes interact with different structures on the surface of HeLa cells. Exp Parasitol 1991; 73(1):1–14.PubMedCrossRefGoogle Scholar
  27. 27.
    Ley V, Robbins ES, Nussenzweig V et al. The exit of Trypanosoma cruzi from the phagosome is inhibited by raising the pH of acidic compartments. J Exp Med 1990; 171(2):401–413.PubMedCrossRefGoogle Scholar
  28. 28.
    Andrade LO, Andrews NW. The Trypanosoma cruzi-host-cell interplay: Location, invasion, retention. Nat Rev Microbiol 2005; 3(10):819–823.PubMedCrossRefGoogle Scholar
  29. 29.
    Burleigh BA. Host cell signaling and Trypanosoma cruzi invasion: Do all roads lead to lysosomes? Sci STKE 2005; 2005(293):pe36.PubMedCrossRefGoogle Scholar
  30. 30.
    Wilkowsky SE, Barbieri MA, Stahl PD et al. Regulation of Trypanosoma cruzi invasion of nonphagocytic cells by the endocytically active GTPases dynamin, Rab5, and Rab7. Biochem Biophys Res Commun 2002; 291(3):516–521.PubMedCrossRefGoogle Scholar
  31. 31.
    Andrade LO, Andrews NW. Lysosomal fusion is essential for the retention of Trypanosoma cruzi inside host cells. J Exp Med 2004; 200(9):1135–1143.PubMedCrossRefGoogle Scholar
  32. 32.
    Woolsey AM, Sunwoo L, Petersen CA et al. Novel PI 3-kinase-dependent mechanisms of trypanosome invasion and vacuole maturation. J Cell Sci 2003; 116 (Pt 17):3611–3622.PubMedCrossRefGoogle Scholar
  33. 33.
    Schenkman S, Robbins ES, Nussenzweig V. Attachment of Trypanosoma cruzi to mammalian cells requires parasite energy, and invasion can be independent of the target cell cytoskeleton. Infect Immun 1991; 59(2):645–654.PubMedGoogle Scholar
  34. 34.
    Burleigh BA, Andrews NW. Signaling and host cell invasion by Trypanosoma cruzi. Curr Opin Microbiol 1998; 1(4):461–465.PubMedCrossRefGoogle Scholar
  35. 35.
    DosReis GA, Freirede-Lima CG, Nunes MP et al. The importance of aberrant T-cell responses in Chagas disease. Trends Parasitol 2005; 21(5):237–243.PubMedCrossRefGoogle Scholar
  36. 36.
    Colli W. Trans-sialidase: A unique enzyme activity discovered in the protozoan Trypanosoma cruzi. FASEB J 1993; 7(13):1257–1264.PubMedGoogle Scholar
  37. 37.
    El-Sayed NM, Myler PJ, Bartholomeu DC et al. The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease. Science 2005; 309(5733):409–415.PubMedCrossRefGoogle Scholar
  38. 38.
    Schenkman S, Eichinger D, Pereira ME et al. Structural and functional properties of Trypanosoma trans-sialidase. Annu Rev Microbiol 1994; 48:499–523.PubMedCrossRefGoogle Scholar
  39. 39.
    Frasch AC. Functional diversity in the trans-sialidase and mucin families in Trypanosoma cruzi. Parasitol Today 2000; 16(7):282–286.PubMedCrossRefGoogle Scholar
  40. 40.
    Cross GA, Takle GB. The surface trans-sialidase family of Trypanosoma cruzi. Annu Rev Microbiol 1993; 47:385–411.PubMedCrossRefGoogle Scholar
  41. 41.
    Giordano R, Fouts DL, Tewari D et al. Cloning of a surface membrane glycoprotein specific for the infective form of Trypanosoma cruzi having adhesive properties to laminin. J Biol Chem 1999; 274(6):3461–3468.PubMedCrossRefGoogle Scholar
  42. 42.
    El-Sayed NM, Myler PJ, Blandin G et al. Comparative genomics of trypanosomatid parasitic protozoa. Science 2005; 309(5733):404–409.PubMedCrossRefGoogle Scholar
  43. 43.
    Campo V, Di Noia JM, Buscaglia CA et al. Differential accumulation of mutations localized in particular domains of the mucin genes expressed in the vertebrate host stage of Trypanosoma cruzi. Mol Biochem Parasitol 2004; 133(1):81–91.PubMedCrossRefGoogle Scholar
  44. 44.
    Katzin AM, Colli W. Lectin receptors in Trypanosoma cruzi. An N-acetyl-D-glucosamine-containing surface glycoprotein specific for the trypomastigote stage. Biochim Biophys Acta 1983; 727(2):403–411.PubMedCrossRefGoogle Scholar
  45. 45.
    Ruiz RC, Favoreto Jr S, Dorta ML et al. Infectivity of Trypanosoma cruzi strains is associated with differential expression of surface glycoproteins with differential Ca2+ signalling activity. Biochem J 1998; 330 (Pt l):505–511.PubMedGoogle Scholar
  46. 46.
    Kahn SJ, Nguyen D, Norsen J et al. Trypanosoma cruzi: Monoclonal antibodies to the surface glycoprotein superfamily differentiate subsets of the 85-kDa surface glycoproteins and confirm simultaneous expression of variant 85-kDa surface glycoproteins. Exp Parasitol 1999; 92(1):48–56.PubMedCrossRefGoogle Scholar
  47. 47.
    Fouts DL, Ruef BJ, Ridley PT et al. Nucleotide sequence and transcription of a trypomastigote surface antigen gene of Trypanosoma cruzi. Mol Biochem Parasitol 1991; 46(2):189–200.PubMedCrossRefGoogle Scholar
  48. 48.
    Franco FR, Paranhos-Bacalla GS, Yamauchi LM et al. Characterization of a cDNA clone encoding the carboxy-terminal domain of a 90-kilodalton surface antigen of Trypanosoma cruzi metacyclic trypomastigotes. Infect Immun 1993; 61(10):4196–4201.PubMedGoogle Scholar
  49. 49.
    Goncalves MF, Umezawa ES, Katzin AM et al. Trypanosoma cruzi: Shedding of surface antigens as membrane vesicles. Exp Parasitol 1991; 72(1):43–53.PubMedCrossRefGoogle Scholar
  50. 50.
    Schenkman S, Jiang MS, Hart GW et al. A novel cell surface trans-sialidase of Trypanosoma cruzi generates a stage-specific epitope required for invasion of mammalian cells. Cell 1991; 65(7):1117–1125.PubMedCrossRefGoogle Scholar
  51. 51.
    Schenkman S, Eichinger D. Trypanosoma cruzi trans-sialidase and cell invasion. Parasitol Today 1993; 9(6):218–222.PubMedCrossRefGoogle Scholar
  52. 52.
    Tomlinson S, Pontes de Carvalho LC, Vandekerckhove F et al. Role of sialic acid in the resistance of Trypanosoma cruzi trypomastigotes to complement. J Immunol 1994; 153(7):3141–3147.PubMedGoogle Scholar
  53. 53.
    Gao W, Wortis HH, Pereira MA. The Trypanosoma cruzi trans-sialidase is a T cell-independent B cell mitogen and an inducer of nonspecific Ig secretion. Int Immunol 2002; 14(3):299–308.PubMedCrossRefGoogle Scholar
  54. 54.
    Ming M, Chuenkova M, Ortega-Barria E et al. Mediation of Trypanosoma cruzi invasion by sialic acid on the host cell and trans-sialidase on the trypanosome. Mol Biochem Parasitol 1993; 59(2):243–252.PubMedCrossRefGoogle Scholar
  55. 55.
    Todeschini AR, Dias WB, Girard MF et al. Enzymatically inactive trans-sialidase from Trypanosoma cruzi binds sialyl and beta-galactopyranosyl residues in a sequential ordered mechanism. J Biol Chem 2004; 279(7):5323–5328.PubMedCrossRefGoogle Scholar
  56. 56.
    Ciavaglia Mdo C, de Carvalho TU, de Souza W. Interaction of Trypanosoma cruzi with cells with altered glycosylation patterns. Biochem Biophys Res Commun 1993; 193(2):718–721.PubMedCrossRefGoogle Scholar
  57. 57.
    Lopez M, Huynh C, Andrade LO et al. Role for sialic acid in the formation of tight lysosome-derived vacuoles during Trypanosoma cruzi invasion. Mol Biochem Parasitol 2002; 119(1):141–145.PubMedCrossRefGoogle Scholar
  58. 58.
    Hohenester E, Engel J. Domain structure and organisation in extracellular matrix proteins. Matrix Biol 2002; 21(2):115–128.PubMedCrossRefGoogle Scholar
  59. 59.
    Giordano R, Chammas R, Veiga SS et al. Trypanosoma cruzi binds to laminin in a carbohydrate-independent way. Braz J Med Biol Res 1994; 27(9):2315–2318.PubMedGoogle Scholar
  60. 60.
    Giordano R, Chammas R, Veiga SS et al. An acidic component of the heterogeneous Tc-85 protein family from the surface of Trypanosoma cruzi is a laminin binding glycoprotein. Mol Biochem Parasitol 1994; 65(1):85–94.PubMedCrossRefGoogle Scholar
  61. 61.
    Ulrich H, Magdesian MH, Alves MJ et al. In vitro selection of RNA aptamers that bind to cell adhesion receptors of Trypanosoma cruzi and inhibit cell invasion. J Biol Chem 2002; 277(23):20756–20762.PubMedCrossRefGoogle Scholar
  62. 62.
    Marroquin-Quelopana M, Oyama Jr S, Aguiar Pertinhez T et al. Modeling the Trypanosoma cruzi Tc85-11 protein and mapping the laminin-binding site. Biochem Biophys Res Commun 2004; 325(2):612–618.PubMedCrossRefGoogle Scholar
  63. 63.
    Velge P, Ouaissi MA, Cornette J et al. Identification and isolation of Trypanosoma cruzi trypomastigote collagen-binding proteins: Possible role in cell-parasite interaction. Parasitology 1988; 97 (Pt 2):255–268.PubMedCrossRefGoogle Scholar
  64. 64.
    Calvet CM, Meuser M, Almeida D et al. Trypanosoma cruzi-cardiomyocyte interaction: Role of fibronectin in the recognition process and extracellular matrix expression in vitro and in vivo. Exp Parasitol 2004; 107(1–2):20–30.PubMedCrossRefGoogle Scholar
  65. 65.
    Herrera EM, Ming M, Ortega-Barria E et al. Mediation of Trypanosoma cruzi invasion by heparan sulfate receptors on host cells and penetrin counter-receptors on the trypanosomes. Mol Biochem Parasitol 1994; 65(1):73–83.PubMedCrossRefGoogle Scholar
  66. 66.
    Calvet CM, Toma L, De Souza FR et al. Heparan sulfate proteoglycans mediate the invasion of cardiomyocytes by Trypanosoma cruzi. J Eukaryot Microbiol 2003; 50(2):97–103.PubMedCrossRefGoogle Scholar
  67. 67.
    Ouaissi MA, Cornette J, Capron A. Trypanosoma cruzi: Modulation of parasite-cell interaction by plasma fibronectin. Eur J Immunol 1985; 15(11):1096–1101.PubMedCrossRefGoogle Scholar
  68. 68.
    Ouaissi MA, Afchain D, Capron A et al. Fibronectin receptors on Trypanosoma cruzi trypomastigptes and their biological function. Nature 1984; 308(5957):380–382.PubMedCrossRefGoogle Scholar
  69. 69.
    Fernandez MA, Munoz-Fernandez MA, Fresno M. Involvement of beta 1 integrins in the binding and entry of Trypanosoma cruzi into human macrophages. Eur J Immunol 1993; 23(2):552–557.PubMedCrossRefGoogle Scholar
  70. 70.
    Ouaissi MA. Role of the RGD sequence in parasite adhesion to host cells. Parasitol Today 1988; 4(6):169–173.PubMedCrossRefGoogle Scholar
  71. 71.
    Ruoslahti E. The RGD story: A personal account. Matrix Biol 2003; 22(6):459–465.PubMedCrossRefGoogle Scholar
  72. 72.
    Vray B, Camby I, Vercruysse V et al. Up-regulation of galectin-3 and its ligands by Trypanosoma cruzi infection with modulation of adhesion and migration of murine dendritic cells. Glycobiology 2004; 14(7):647–657.PubMedCrossRefGoogle Scholar
  73. 73.
    Magdesian MH, Giordano R, Ulrich H et al. Infection by Trypanosoma cruzi. Identification of a parasite ligand and its host cell receptor. J Biol Chem 2001; 276(22):19382–19389.PubMedCrossRefGoogle Scholar
  74. 74.
    Masocha W, Robertson B, Rottenberg ME et al. Cerebral vessel laminins and IFN-gamma define Trypanosoma brucei brucei penetration of the blood-brain barrier. J Clin Invest 2004; H4(5):689–694.Google Scholar
  75. 75.
    Andrade SG, Grimaud JA, Stocker-Guerret S. Sequential changes of the connective matrix components of the myocardium (fibronectin and laminin) and evolution of cardiac fibrosis in mice infected with Trypanosoma cruzi. Am J Trop Med Hyg 1989; 40(3):252–260.PubMedGoogle Scholar
  76. 76.
    Pinho RT, Vannier-Santos MA, Alves CR et al. Effect of Trypanosoma cruzi released antigens binding to noninfected cells on anti-parasite antibody recognition and expression of extracellular matrix components. Acta Trop 2002; 83(2):103–115.PubMedCrossRefGoogle Scholar
  77. 77.
    Zuniga E, Gruppi A, Hirabayashi J et al. Regulated expression and effect of galectin-1 on Trypanosoma cruzi-infected macrophages: Modulation of microbicidal activity and survival. Infect Immun 2001; 69(11):6804–6812.PubMedCrossRefGoogle Scholar
  78. 78.
    Ramirez MI, Ruiz Rde C, Araya JE et al. Involvement of the stage-specific 82-kilodalton adhesion molecule of Trypanosoma cruzi metacyclic trypomastigotes in host cell invasion. Infect Immun 1993; 61(9):3636–3641.PubMedGoogle Scholar
  79. 79.
    Ellington AD, Szostak JW. In vitro selection of RNA molecules that bind specific ligands. Nature 1990; 346(6287):818–822.PubMedCrossRefGoogle Scholar
  80. 80.
    Tuerk C, Gold L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 1990; 249(4968):505–510.PubMedCrossRefGoogle Scholar
  81. 81.
    Ulrich H, Alves MJ, Colli W. RNA and DNA aptamers as potential tools to prevent cell adhesion in disease. Braz J Med Biol Res 2001; 34(3):295–300.PubMedCrossRefGoogle Scholar
  82. 82.
    Turner CW, Lima MF, Villalta F. Trypanosoma cruzi uses a 45-kDa mucin for adhesion to mammalian cells. Biochem Biophys Res Commun 2002; 290(1):29–34.PubMedCrossRefGoogle Scholar
  83. 83.
    Marcipar IS, Welchen E, Roodveldt C et al. Purification of the 67-kDa lectin-like glycoprotein of Trypanosoma cruzi, LLGP-67, and its evaluation as a relevant antigen for the diagnosis of human infection. FEMS Microbiol Lett 2003; 220(1):149–154.PubMedCrossRefGoogle Scholar
  84. 84.
    Scharfstein J, Schmitz V, Morandi V et al. Host cell invasion by Trypanosoma cruzi is potentiated by activation of bradykinin B(2) receptors. J Exp Med 2000; 192(9):1289–1300.PubMedCrossRefGoogle Scholar
  85. 85.
    Ming M, Ewen ME, Pereira ME. Trypanosome invasion of mammalian cells requires activation of the TGF beta signaling pathway. Cell 1995; 82(2):287–296.PubMedCrossRefGoogle Scholar
  86. 86.
    Aparicio IM, Scharfstein J, Lima AP. A new cruzipain-mediated pathway of human cell invasion by Trypanosoma cruzi requires trypomastigote membranes. Infect Immun 2004; 72(10):5892–5902.PubMedCrossRefGoogle Scholar
  87. 87.
    Moro A, Ruiz-Cabello F, Fernandez-Cano A et al. Secretion by Trypanosoma cruzi of a peptidyl-prolyl cis-trans isomerase involved in cell infection. EMBO J 1995; 14(11):2483–2490.PubMedGoogle Scholar
  88. 88.
    Cuevas IC, Cazzulo JJ, Sanchez DO. gp63 homologues in Trypanosoma cruzi: Surface antigens with metalloprotease activity and a possible role in host cell infection. Infect Immun 2003; 71(10):5739–5749.PubMedCrossRefGoogle Scholar
  89. 89.
    Santana JM, Grellier P, Schrevel J et al. A Trypanosoma cruzi-secreted 80 kDa proteinase with specificity for human collagen types I and IV. Biochem J 1997; 325 (Pt 1):129–137.PubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2008

Authors and Affiliations

  1. 1.Departamento de Bioquímica, Instituto de QuímicaUniversidade de São PauloSao PauloBrazil

Personalised recommendations