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Infect Immun. Sep 1996; 64(9): 3884–3892.
PMCID: PMC174307

Invasive phenotype of Trypanosoma cruzi restricted to a population expressing trans-sialidase.


Trypanosoma cruzi expresses a developmentally regulated trans-sialidase implicated in the pathogenesis of Chagas' disease. On inhabitation of the extracellular milieu of cultured cells by infective trypomastigotes, the enzyme is restricted to a small (20 to 30%) population of parasites. The biological significance of trans-sialidase expression on this subset, termed TS+, and not on the majority (70 to 80%) of morphologically similar trypanosomes, named TS-, is unknown. To determine the roles of the TS+ and TS- subsets in T. cruzi invasion, we prepared pure populations of TS- and TS+ trypanosomes using magnetic beads coated with a monoclonal antibody specific for the tandem repeat unit of the trans-sialidase C terminus. After removal of nonadherent TS- trypomastigotes, the TS+ trypomastigotes were isolated from the beads by specific elusion with a synthetic peptide epitope of the trans-sialidase monoclonal antibody. Confirmation of TS+ and TS- phenotypes was obtained by immunofluorescence, immunoblotting, and sialidase or sialyl transferase activity measurements. The TS+ trypanosomes were highly invasive, as they attached to, penetrated, and thrived in cultured mammalian cells much more efficiently than did unfractionated parasites. The critical role of the trans-sialidase in invasion was underscored by the observation that infection was neutralized by human antibodies to transsialidase. What's more, the TS- parasites, in sharp contrast to their TS+ counterparts, were extremely inefficient in invading epithelial cells and fibroblasts. Further, introduction of small amounts of exogenous trans-sialidase into suspensions of nonpenetrating TS- parasites converted them to a highly invasive phenotype indistinguishable from that of the TS+ population. Rescue of the invasive phenotype was specific for the T. cruzi enzyme, for it didn't happen with bacterial and viral sialidases. The in vitro results were confirmed in the murine model of Chagas' disease, as TS- trypomastigotes were relatively avirulent while TS+ trypomastigotes were more virulent than unfractionated parasites.

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Selected References

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  • Bjerke T, Nielsen S, Helgestad J, Nielsen BW, Schiøtz PO. Purification of human blood basophils by negative selection using immunomagnetic beads. J Immunol Methods. 1993 Jan 4;157(1-2):49–56. [PubMed]
  • Burleigh BA, Andrews NW. The mechanisms of Trypanosoma cruzi invasion of mammalian cells. Annu Rev Microbiol. 1995;49:175–200. [PubMed]
  • Cavallesco R, Pereira ME. Antibody to Trypanosoma cruzi neuraminidase enhances infection in vitro and identifies a subpopulation of trypomastigotes. J Immunol. 1988 Jan 15;140(2):617–625. [PubMed]
  • Chuenkova M, Pereira ME. Trypanosoma cruzi trans-sialidase: enhancement of virulence in a murine model of Chagas' disease. J Exp Med. 1995 May 1;181(5):1693–1703. [PMC free article] [PubMed]
  • de Titto EH, Israelski D, Araujo FG. Circulating Trypanosoma cruzi from the same cloned population show differences in the ability to infect cells and to cause lethal infection in mice. Experientia. 1987 Dec 1;43(11-12):1227–1229. [PubMed]
  • Geng JG, Bevilacqua MP, Moore KL, McIntyre TM, Prescott SM, Kim JM, Bliss GA, Zimmerman GA, McEver RP. Rapid neutrophil adhesion to activated endothelium mediated by GMP-140. Nature. 1990 Feb 22;343(6260):757–760. [PubMed]
  • Grabel LB, Rosen SD, Martin GR. Teratocarcinoma stem cells have a cell surface carbohydrate-binding component implicated in cell-cell adhesion. Cell. 1979 Jul;17(3):477–484. [PubMed]
  • Herrera EM, Ming M, Ortega-Barria E, Pereira ME. Mediation of Trypanosoma cruzi invasion by heparan sulfate receptors on host cells and penetrin counter-receptors on the trypanosomes. Mol Biochem Parasitol. 1994 May;65(1):73–83. [PubMed]
  • Jackson CJ, Garbett PK, Nissen B, Schrieber L. Binding of human endothelium to Ulex europaeus I-coated Dynabeads: application to the isolation of microvascular endothelium. J Cell Sci. 1990 Jun;96(Pt 2):257–262. [PubMed]
  • Manyonda IT, Soltys AJ, Hay FC. A critical evaluation of the magnetic cell sorter and its use in the positive and negative selection of CD45RO+ cells. J Immunol Methods. 1992 Apr 27;149(1):1–10. [PubMed]
  • Marlin SD, Staunton DE, Springer TA, Stratowa C, Sommergruber W, Merluzzi VJ. A soluble form of intercellular adhesion molecule-1 inhibits rhinovirus infection. Nature. 1990 Mar 1;344(6261):70–72. [PubMed]
  • Ming M, Chuenkova M, Ortega-Barria E, Pereira ME. Mediation of Trypanosoma cruzi invasion by sialic acid on the host cell and trans-sialidase on the trypanosome. Mol Biochem Parasitol. 1993 Jun;59(2):243–252. [PubMed]
  • Ming M, Ewen ME, Pereira ME. Trypanosome invasion of mammalian cells requires activation of the TGF beta signaling pathway. Cell. 1995 Jul 28;82(2):287–296. [PubMed]
  • Ortega-Barria E, Pereira ME. A novel T. cruzi heparin-binding protein promotes fibroblast adhesion and penetration of engineered bacteria and trypanosomes into mammalian cells. Cell. 1991 Oct 18;67(2):411–421. [PubMed]
  • Parodi AJ, Pollevick GD, Mautner M, Buschiazzo A, Sanchez DO, Frasch AC. Identification of the gene(s) coding for the trans-sialidase of Trypanosoma cruzi. EMBO J. 1992 May;11(5):1705–1710. [PMC free article] [PubMed]
  • Pereira ME. A developmentally regulated neuraminidase activity in Trypanosoma cruzi. Science. 1983 Mar 25;219(4591):1444–1446. [PubMed]
  • Pereira ME, Mejia JS, Ortega-Barria E, Matzilevich D, Prioli RP. The Trypanosoma cruzi neuraminidase contains sequences similar to bacterial neuraminidases, YWTD repeats of the low density lipoprotein receptor, and type III modules of fibronectin. J Exp Med. 1991 Jul 1;174(1):179–191. [PMC free article] [PubMed]
  • Prioli RP, Mejia JS, Pereira ME. Monoclonal antibodies against Trypanosoma cruzi neuraminidase reveal enzyme polymorphism, recognize a subset of trypomastigotes, and enhance infection in vitro. J Immunol. 1990 Jun 1;144(11):4384–4391. [PubMed]
  • Prioli RP, Ortega-Barria E, Mejia JS, Pereira ME. Mapping of a B-cell epitope present in the neuraminidase of Trypanosoma cruzi. Mol Biochem Parasitol. 1992 May;52(1):85–96. [PubMed]
  • Rosenberg IA, Prioli RP, Mejia JS, Pereira ME. Differential expression of Trypanosoma cruzi neuraminidase in intra- and extracellular trypomastigotes. Infect Immun. 1991 Jan;59(1):464–466. [PMC free article] [PubMed]
  • Schenkman S, Eichinger D, Pereira ME, Nussenzweig V. Structural and functional properties of Trypanosoma trans-sialidase. Annu Rev Microbiol. 1994;48:499–523. [PubMed]
  • Schenkman S, Jiang MS, Hart GW, Nussenzweig V. A novel cell surface trans-sialidase of Trypanosoma cruzi generates a stage-specific epitope required for invasion of mammalian cells. Cell. 1991 Jun 28;65(7):1117–1125. [PubMed]
  • Schenkman S, Pontes de Carvalho L, Nussenzweig V. Trypanosoma cruzi trans-sialidase and neuraminidase activities can be mediated by the same enzymes. J Exp Med. 1992 Feb 1;175(2):567–575. [PMC free article] [PubMed]
  • Scudder P, Doom JP, Chuenkova M, Manger ID, Pereira ME. Enzymatic characterization of beta-D-galactoside alpha 2,3-trans-sialidase from Trypanosoma cruzi. J Biol Chem. 1993 May 5;268(13):9886–9891. [PubMed]
  • Tardieux I, Webster P, Ravesloot J, Boron W, Lunn JA, Heuser JE, Andrews NW. Lysosome recruitment and fusion are early events required for trypanosome invasion of mammalian cells. Cell. 1992 Dec 24;71(7):1117–1130. [PubMed]
  • Vremec D, Zorbas M, Scollay R, Saunders DJ, Ardavin CF, Wu L, Shortman K. The surface phenotype of dendritic cells purified from mouse thymus and spleen: investigation of the CD8 expression by a subpopulation of dendritic cells. J Exp Med. 1992 Jul 1;176(1):47–58. [PMC free article] [PubMed]

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