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Trypanosoma cruzi Trans-Sialidase: Structural Features and Biological Implications

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Proteins and Proteomics of Leishmania and Trypanosoma

Abstract

Trypanosoma cruzi trans-sialidase (TcTS) has intrigued researchers all over the world since it was shown that T. cruzi incorporates sialic acid through a mechanism independent of sialyltransferases. The enzyme has being involved in a vast myriad of functions in the biology of the parasite and in the pathology of Chagas’ disease. At the structural level experiments trapping the intermediate with fluorosugars followed by peptide mapping, X-ray crystallography, molecular modeling and magnetic nuclear resonance have opened up a three-dimensional understanding of the way this enzyme works. Herein we review the multiple biological roles of TcTS and the structural studies that are slowly revealing the secrets underlining an efficient sugar transfer activity rather than simple hydrolysis by TcTS.

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Abbreviations

4-MUNeu5Ac:

4-methylumbelliferyl-N-acetyl neuraminic acid

Galf :

Galactofuranose

Galp :

Galactopyranose

GlcNAc:

N-acetylglucosamine

Neu5Ac:

N-acetylneuraminic

Neu5Gc:

N-glycolylneuraminic acid

NGF:

Nerve growth factor receptor

pNPNeu5Ac:

p-nitrophenyl-N-acetyl-neuraminic acid

SAPA:

Shed acute phase antigen

Sias:

Sialic acids

Siglecs:

Sia-binding Ig-like lectin

TcTS:

Trypanosoma cruzi trans-sialidase

TSs:

Trans-sialidase family

UTR:

Untranslated regions

References

  • Agrellos OA, Jones C, Todeschini AR et al (2003) A novel sialylated and galactofuranose-containing O-linked glycan, Neu5Acalpha2-3Galpbeta1-6(Galfbeta1-4)GlcNAc, is expressed on the sialoglycoprotein of Trypanosoma cruzi Dm28c. Mol Biochem Parasitol 126:93–96

    CAS  PubMed  Google Scholar 

  • Agusti R, Couto AS, Campetella OE et al (1997) The trans-sialidase of Trypanosoma cruzi is anchored by two different lipids. Glycobiology 7:731–735

    CAS  PubMed  Google Scholar 

  • Agusti R, Couto AS, Campetella O et al (1998) Mol Biochem Parasitol 9:123–131

    Google Scholar 

  • Agustí R, Paris G, Ratier L et al (2004) Lactose derivatives are inhibitors of Trypanosoma cruzi trans-sialidase activity toward conventional substrates in vitro and in vivo. Glycobiology 14:659–670

    PubMed  Google Scholar 

  • Agustí R, Giorgi ME, de Lederkremer RM (2007) The trans-sialidase from Trypanosoma cruzi efficiently transfers alpha-(2,3)-linked N-glycolylneuraminic acid to terminal beta-galactosyl units. Carbohydr Res 342:2465–2469

    PubMed  Google Scholar 

  • Almeida IC, Ferguson MA, Schenkman S, Travassos LR (1994) Lytic anti-alpha-galactosyl antibodies from patients with chronic Chagas’ disease recognize novel O-linked oligosaccharides on mucin-like glycosyl-phosphatidylinositol-anchored glycoproteins of Trypanosoma cruzi. Biochem J 304:793–802

    CAS  PubMed  Google Scholar 

  • Amaya MF, Watts AG, Damager I et al (2004) Structural insights into the catalytic mechanism of Trypanosoma cruzi trans-sialidase. Structure 12:775–784

    CAS  PubMed  Google Scholar 

  • Amith SR, Jayanth P, Franchuk S et al (2010) Neu1 desialylation of sialyl alpha-2,3-linked beta-galactosyl residues of TOLL-like receptor 4 is essential for receptor activation and cellular signaling. Cell Signal 22:314–324

    CAS  PubMed  Google Scholar 

  • Andrade LO, Andrews NW (2004) Lysosomal fusion is essential for the retention of Trypanosoma cruzi inside host cells. J Exp Med 200:1135–1143

    Google Scholar 

  • Andrews NW (2002) Lysosomes and the plasma membrane: trypanosomes reveal a secret relationship. J Cell Biol 158:389–394

    CAS  PubMed  Google Scholar 

  • Andrews NW, Abrams CK, Slatin SL, Griffiths GA (1990) T. Cruzi-secreted protein immunologically related to the complement component C9: evidence for membrane pore-forming activity at low pH. Cell 61:1277–1287

    CAS  PubMed  Google Scholar 

  • Araújo-Jorge TC, De Souza W (1988) Interaction of Trypanosoma cruzi with macrophages. Involvement of surface galactose and N-acetyl-D-galactosamine residues on the recognition process. Acta Trop 45:127–136

    PubMed  Google Scholar 

  • Aridgides D, Salvador R, Pereiraperrin M (2013) Trypanosoma cruzi coaxes cardiac fibroblasts into preventing cardiomyocyte death by activating nerve growth factor receptor TrkA. PLoS One 8:e57450

    CAS  PubMed  Google Scholar 

  • Bayer-Santos E, Gentil LG, Cordero EM et al (2012) Regulatory elements in the 3′ untranslated region of the GP82 glycoprotein are responsible for its stage-specific expression in Trypanosoma cruzi metacyclic trypomastigotes. Acta Trop 123:230–233

    CAS  PubMed  Google Scholar 

  • Belen-Carrillo M, Gao W, Herrera M et al (2000) Heterologous expression of Trypanosoma cruzi trans-sialidase in leishmania major enhances virulence. Infect Immun 68:2728–2734

    CAS  PubMed  Google Scholar 

  • Briones MR, Egima CM, Schenkman S (1995) Trypanosoma cruzi trans-sialidase gene lacking C-terminal repeats and expressed in epimastigote forms. Mol Biochem Parasitol 70:9–17

    CAS  PubMed  Google Scholar 

  • Buchini S, Buschiazzo A, Withers SG (2008) A new generation of specific Trypanosoma cruzi trans-sialidase inhibitors. Angew Chem Int Ed Engl 47:2700–2703

    CAS  PubMed  Google Scholar 

  • Buscaglia CA, Campetella O, Leguizamón MS, Frasch AC (1998) The repetitive domain of Trypanosoma cruzi trans-sialidase enhances the immune response against the catalytic domain. J Infect Dis 177:431–436

    CAS  PubMed  Google Scholar 

  • Buscaglia CA, Alfonso J, Campetella O, Frasch AC (1999) Tandem amino acid repeats from Trypanosoma cruzi shed antigens increase the half-life of proteins in blood. Blood 93:2025–2032

    CAS  PubMed  Google Scholar 

  • Buscaglia CA, Campo VA, Frasch AC, DiNoia JM (2006) Trypanosoma cruzi surface mucins: host-dependent coat diversity. Nat Rev Microbiol 4:229–236

    CAS  PubMed  Google Scholar 

  • Buschiazzo A, Tavares GA, Campetella O et al (2000) Structural basis of sialyltransferase activity in trypanosomal sialidases. EMBO J 19:16–24

    CAS  PubMed  Google Scholar 

  • Buschiazzo A, Amaya MF, Cremona ML et al (2002) The crystal structure and mode of action of trans-sialidase, a key enzyme in Trypanosoma cruzi pathogenesis. Mol Cell 10:757–768

    CAS  PubMed  Google Scholar 

  • Buschiazzo A, Muiá R, Larrieux N et al (2012) Trypanosoma cruzi trans-sialidase in complex with a neutralizing antibody: structure/function studies towards the rational design of inhibitors. PLoS Pathog 8:e1002474

    CAS  PubMed  Google Scholar 

  • Campetella OE, Uttaro AD, Parodi AJ, Frasch AC (1994) A recombinant Trypanosoma cruzi trans-sialidase lacking the amino acid repeats retains the enzymatic activity. Mol Biochem Parasitol 64:337–340

    CAS  PubMed  Google Scholar 

  • Campo VL, Sesti-Costa R, Carneiro ZA et al (2012) Design, synthesis and the effect of 1,2,3-triazole sialylmimetic neoglycoconjugates on Trypanosoma cruzi and its cell surface trans-sialidase. Bioorg Med Chem 20:145–156

    CAS  PubMed  Google Scholar 

  • Caradonna KL, Burleigh BA (2011) Mechanisms of host cell invasion by Trypanosoma cruzi. Adv Parasitol 76:33–61

    PubMed  Google Scholar 

  • Carvalho ST, Sola-Penna M, Oliveira IA et al (2010) A new class of mechanism-based inhibitors for Trypanosoma cruzi trans-sialidase and their influence on parasite virulence. Glycobiology 20:1034–1045

    CAS  PubMed  Google Scholar 

  • Cazzulo JJ, Frasch AC (1992) SAPA/trans-sialidase and cruzipain: two antigens from Trypanosoma cruzi contain immunodominant but enzymatically inactive domains. FASEB J 6:3259–3264

    CAS  PubMed  Google Scholar 

  • Chaves LB, Briones MR, Schenkman S (1993) Trans-sialidase from Trypanosoma cruzi epimastigotes is expressed at the stationary phase and is different from the enzyme expressed in trypomastigotes. Mol Biochem Parasitol 61:97–106

    CAS  PubMed  Google Scholar 

  • Chuenkova M, Pereira ME (1995) Trypanosoma cruzi trans-sialidase: enhancement of virulence in a murine model of Chagas’ disease. J Exp Med 181:1693–1703

    CAS  PubMed  Google Scholar 

  • Chuenkova M, Pereira M, Taylor G (1999) Trans-sialidase of Trypanosoma cruzi: location of galactose-binding site(s). Biochem Biophys Res Commun 262:549–556

    CAS  PubMed  Google Scholar 

  • Chuenkova MV, Pereira MA (2000) A trypanosomal protein synergizes with the cytokines ciliary neurotrophic factor and leukemia inhibitory factor to prevent apoptosis of neuronal cells. Mol Biol Cell 11:1487–1498

    CAS  PubMed  Google Scholar 

  • Chuenkova MV, Pereira MA (2003) PDNF, a human parasite-derived mimic of neurotrophic factors, prevents caspase activation, free radical formation, and death of dopaminergic cells exposed to the parkinsonism-inducing neurotoxin MPP+. Brain Res Mol Brain Res 119:50–61

    CAS  PubMed  Google Scholar 

  • Chuenkova MV, PereiraPerrin MA (2005) Synthetic peptide modeled on PDNF, Chagas’ disease parasite neurotrophic factor, promotes survival and differentiation of neuronal cells through TrkA receptor. Biochemistry 44:15685–15694

    CAS  PubMed  Google Scholar 

  • Chuenkova MV, Pereiraperrin M (2011) Neurodegeneration and neuroregeneration in Chagas disease. Adv Parasitol 76:195–233

    PubMed  Google Scholar 

  • Ciavaglia MC, de Carvalho TU, de Souza W (1993) Interaction of Trypanosoma cruzi with cells with altered glycosylation patterns. Biochem Biophys Res Commun 193:718–721

    CAS  Google Scholar 

  • Cortez C, Yoshida N, Bahia D, Sobreira TJ (2012a) Structural basis of the interaction of a Trypanosoma cruzi surface molecule implicated in oral infection with host cells and gastric mucin. PLoS One 7:e42153

    CAS  PubMed  Google Scholar 

  • Cortez C, Martins RM, Alves RM et al (2012b) Differential infectivity by the oral route of Trypanosoma cruzi lineages derived from Y strain. PLoS Negl Trop Dis 6:e1804

    CAS  PubMed  Google Scholar 

  • Cremona ML, Sánchez DO, Frasch AC, Campetella OA (1995) Single tyrosine differentiates active and inactive Trypanosoma cruzi trans-sialidases. Gene 160:123–128

    CAS  PubMed  Google Scholar 

  • Cremona ML, Campetella O, Sánchez DO, Frasch AC (1999) Enzymically inactive members of the trans-sialidase family from Trypanosoma cruzi display beta-galactose binding activity. Glycobiology 9:581–587

    CAS  PubMed  Google Scholar 

  • de Melo-Jorge M, PereiraPerrin M (2007) The Chagas’ disease parasite Trypanosoma cruzi exploits nerve growth factor receptor TrkA to infect mammalian hosts. Cell Host Microbe 1:251–261

    PubMed  Google Scholar 

  • Damager I, Buchini S, Amaya MF et al (2008) Kinetic and mechanistic analysis of Trypanosoma cruzi trans-sialidase reveals a classical ping-pong mechanism with acid/base catalysis. Biochemistry 47:3507–3512

    CAS  PubMed  Google Scholar 

  • Demir O, Roitberg AE (2009) Modulation of catalytic function by differential plasticity of the active site: case study of Trypanosoma cruzi trans-sialidase and Trypanosoma rangeli sialidase. Biochemistry 48:3398–3406

    CAS  PubMed  Google Scholar 

  • De Pablos LM, Osuna A (2012) Multigene families in Trypanosoma cruzi and their role in infectivity. Infect Immun 80:2258–2264

    PubMed  Google Scholar 

  • De Titto EH, Araújo FG (1988) Serum neuraminidase activity and hematological alterations in acute human Chagas’ disease. Clin Immunol Immunopathol 46:157–161

    PubMed  Google Scholar 

  • Dias WB, Fajardo FD, Graça-Souza AV et al (2008) Endothelial cell signalling induced by trans-sialidase from Trypanosoma cruzi. Cell Microbiol 10:88–99

    CAS  PubMed  Google Scholar 

  • Di Noia JM, D’Orso I, S’anchez DO, Frasch AC (2000) AU-rich elements in the 3’-untranslated region of a new mucin-type gene family of Trypanosoma cruzi confers mRNA instability and modulates translation efficiency. J Biol Chem 275:10218–10227

    PubMed  Google Scholar 

  • dC-Rubin SSC, Schenkman S (2011) Trypanosoma cruzi trans-sialidase as a multifunctional enzyme in Chagas’ disease. Cell Microbiol 14:1522–1530

    Google Scholar 

  • El-Sayed NM et al (2005a) Comparative genomics of trypanosomatid parasitic protozoa. Science 309:404–409

    CAS  PubMed  Google Scholar 

  • El-Sayed NM et al (2005b) The genome sequence of Trypanosoma cruzi, etiologic agent of chagas disease. Science 309:409–415

    CAS  PubMed  Google Scholar 

  • Erdmann H, Steeg C, Koch-Nolte F et al (2009) Sialylated ligands on pathogenic Trypanosoma cruzi interact with Siglec-E (sialic acid-binding Ig-like lectin-E). Cell Microbiol 11:1600–1611

    CAS  PubMed  Google Scholar 

  • Frasch AC (2000) Functional diversity in the trans-sialidase and mucin families in Trypanosoma cruzi. Parasitol Today 16:282–286

    CAS  PubMed  Google Scholar 

  • Freire-de-Lima L, Alisson-Silva F, Carvalho ST et al (2010) Trypanosoma cruzi subverts host cell sialylation and may compromise antigen-specific CD8+ T cell responses. J Biol Chem 285:13388–13396

    CAS  PubMed  Google Scholar 

  • Freire-de-Lima L, Oliveira IA, Neves JL et al (2012) Sialic acid: a sweet swing between mammalian host and Trypanosoma cruzi. Front Immunol 3:356

    CAS  PubMed  Google Scholar 

  • Freitas LM, dos Santos SL, Rodrigues-Luiz GF et al (2011) Genomic analyses, gene expression and antigenic profile of the trans-sialidase superfamily of Trypanosoma cruzi reveal an undetected level of complexity. PLoS One 6:e25914

    CAS  PubMed  Google Scholar 

  • Gao W, Wortis HH, Pereira MA (2002) The Trypanosoma cruzi trans-sialidase is a T cell-independent B cell mitogen and an inducer of non-specific Ig secretion. Int Immunol 14:299–308

    CAS  PubMed  Google Scholar 

  • García GA, Arnaiz MR, Esteva MI et al (2008) Evaluation of immune responses raised against Tc13 antigens of Trypanosoma cruzi in the outcome of murine experimental infection. Parasitology 135:347–357

    PubMed  Google Scholar 

  • Gaskell A, Crennell S, Taylor G (1995) The three domains of a bacterial sialidase: a beta-propeller, an immunoglobulin module and a galactose-binding jelly-roll. Structure 3:1197–1205

    CAS  PubMed  Google Scholar 

  • Gil J, Cimino R, López Quiroga I et al (2011) Reactivity of GST-SAPA antigen of Trypanosoma cruzi against sera from patients with chagas disease and leishmaniasis. Med (B Aires) 71:113–119

    Google Scholar 

  • Giordano R, Chammas R, Veiga SS et al (1994) Trypanosoma cruzi binds to laminin in a carbohydrate-independent way. Braz J Med Biol Res 27:2315–2318

    CAS  PubMed  Google Scholar 

  • Hall BF (1993) Trypanosoma cruzi: mechanisms for entry into host cells. Semin Cell Biol 4:323–333

    CAS  PubMed  Google Scholar 

  • Hall BF, Joiner KA (1991) Strategies of obligate intracellular parasites for evading host defences. Immunol Today 12:A22–A27

    CAS  PubMed  Google Scholar 

  • Hall BF, Joiner KA (1993) Developmentally-regulated virulence factors of Trypanosoma cruzi and their relationship to evasion of host defences. J Eukaryot Microbiol 40:207–213

    Google Scholar 

  • Hall BF, Webster P, Ma AK et al (1992) Desialylation of lysosomal membrane glycoproteins by Trypanosoma cruzi: a role for the surface neuraminidase in facilitating parasite entry into the host cell cytoplasm. J Exp Med 176:313–325

    Google Scholar 

  • Harrison JA, Kartha K, Fournier EJ et al (2011) Probing the acceptor substrate binding site of Trypanosoma cruzi trans-sialidase with systematically modified substrates and glycoside libraries. Org Biomol Chem 9:1653–1660

    CAS  PubMed  Google Scholar 

  • Harrison JA, Kartha KP, Turnbull WB et al (2001) Hydrolase and sialyltransferase activities of Trypanosoma cruzi trans-sialidase towards NeuAc-alpha-2,3-gal-Gal-beta-O-PNP. Bioorg Med Chem Lett 11:141–144

    Google Scholar 

  • Haselhorst T, Wilson JC, Liakatos A et al (2004) NMR spectroscopic and molecular modeling investigations of the trans-sialidase from Trypanosoma cruzi. Glycobiology 14:895–907

    CAS  PubMed  Google Scholar 

  • Jacobs T, Erdmann H, Fleischer B (2010) Molecular interaction of siglecs (sialic acid-binding Ig-like lectins) with sialylated ligands on Trypanosoma cruzi. Eur J Cell Biol 89:113–116

    CAS  PubMed  Google Scholar 

  • Jager AV, De Gaudenzi JG, Cassola A et al (2007) MRNA maturation by two-step trans-splicing/polyadenylation processing in trypanosomes. Proc Natl Acad Sci USA 104:2035–2042

    PubMed  Google Scholar 

  • Jäger AV, Muiá RP, Campetella O (2008) Stage-specific expression of Trypanosoma cruzi trans-sialidase involves highly conserved 3’ untranslated regions. FEMS Microbiol Lett 283:182–188

    Google Scholar 

  • Jones C, Todeschini AR, Agrellos OA et al (2004) Heterogeneity in the biosynthesis of mucin O-glycans from Trypanosoma cruzi tulahuen strain with the expression of novel galactofuranosyl-containing oligosaccharides. Biochemistry 43:11889–11897

    CAS  PubMed  Google Scholar 

  • Kim JH, Resende R, Wennekes T et al (2013) Mechanism-based covalent neuraminidase inhibitors with broad spectrum influenza antiviral activity. Science 340(6128):71–75. doi:10.1126/science.1232552

    CAS  PubMed  Google Scholar 

  • Leguizamón MS, Mocetti E, García Rivello H et al (1999) Trans-sialidase from Trypanosoma cruzi induces apoptosis in cells from the immune system in vivo. J Infect Dis 180:1398–1402

    PubMed  Google Scholar 

  • Lieke T, Gröbe D, Blanchard V et al (2011) Invasion of Trypanosoma cruzi into host cells is impaired by N-propionylmannosamine and other N-acylmannosamines. Glycoconj J 28:31–37

    CAS  PubMed  Google Scholar 

  • Lopez M, Huynh C, Andrade LO, Pypaert M, Andrews NW (2002) Role for sialic acid in the formation of tight lysosome-derived vacuoles during Trypanosoma cruzi invasion. Mol Biochem Parasitol 119:141–145

    CAS  PubMed  Google Scholar 

  • Magdesian MH, Giordano R, Ulrich H et al (2001) Infection by Trypanosoma cruzi. Identification of a parasite ligand and its host cell receptor. J Biol Chem 276:19382–19389

    CAS  PubMed  Google Scholar 

  • Mallimaci MC, Sosa-Estani S, Russomando G (2010) Early diagnosis of congenital Trypanosoma cruzi infection, using shed acute phase antigen, in ushuaia, tierra del fuego, Argentina. Am J Trop Med Hyg 82:55–59

    PubMed  Google Scholar 

  • Mathieu-Daudé F, Lafay B, Touzet O et al (2008) Exploring the FL-160-CRP gene family through sequence variability of the complement regulatory protein (CRP) expressed by the trypomastigote stage of Trypanosoma cruzi. Infect Genet Evol 8:258–266

    PubMed  Google Scholar 

  • Melo-Jorge M, PereiraPerrin M (2004) The Chagas’ disease parasite Trypanosoma cruzi exploits nerve growth factor receptor TrkA to infect mammalian hosts. Cell Host Microbes 1:251–261

    Google Scholar 

  • Mendonça-Previato L, Todeschini AR, Heise N (2008) Chemical structure of major glycoconjugates from parasites. Curr Org Chem 12:926–939

    Google Scholar 

  • Mendonça-Previato L, Todeschini AR, Freire-de-Lima L, Previato JO (2010) The trans-sialidase from Trypanosoma cruzi a putative target for trypanocidal agents. Open Parasitol J 4:111–115

    Google Scholar 

  • Mendonça-Previato L, Penha L, Garcez TC (2013) Addition of α-O-GlcNAc to threonine residues define the post-translational modification of mucin-like molecules in Trypanosoma cruzi. Glycoconj J. doi: 10.1007/s10719-013-9469-7

  • Mitchell FL, Miles SM, Neres J (2010) Tryptophan as a molecular shovel in the glycosyl transfer activity of Trypanosoma cruzi trans-sialidase. Biophys J 98:L38–40

    CAS  PubMed  Google Scholar 

  • Ming M, Chuenkova M, Ortega-Barria E, Pereira ME (1993) Mediation of Trypanosoma cruzi invasion by sialic acid on the host cell and trans-sialidase on the trypanosome. Mol Biochem Parasitol 59:243–252

    CAS  PubMed  Google Scholar 

  • Minoprio P (2001) Parasite polyclonal activators: new targets for vaccination approaches? Int J Parasitol 31:588–591

    CAS  PubMed  Google Scholar 

  • Moraes Barros RR, Marini MM, Antônio CR et al (2012) Anatomy and evolution of telomeric and subtelomeric regions in the human protozoan parasite Trypanosoma cruzi. BMC Genomics 13:229

    PubMed  Google Scholar 

  • Mucci J, Risso MG, Leguizamón MS et al (2006) The trans-sialidase from Trypanosoma cruzi triggers apoptosis by target cell sialylation. Cell Microbiol 8:1086–1095

    CAS  PubMed  Google Scholar 

  • Muiá RP, Yu H, Prescher JA, Hellman U et al (2010) Identification of glycoproteins targeted by Trypanosoma cruzi trans-sialidase, a virulence factor that disturbs lymphocyte glycosylation. Glycobiology 20:833–842

    PubMed  Google Scholar 

  • Neira I, Silva FA, Cortez M, Yoshida N (2003) Involvement of Trypanosoma cruzi metacyclic trypomastigote surface molecule gp82 in adhesion to gastric mucin and invasion of epithelial cells. Infect Immun 71:557–561

    CAS  PubMed  Google Scholar 

  • Nesmelova IV, Ermakova E, Daragan VA et al (2010) Lactose binding to galectin-1 modulates structural dynamics, increases conformational entropy, and occurs with apparent negative cooperativity. J Mol Biol 397:1209–1230

    CAS  PubMed  Google Scholar 

  • Nozaki T, Cross GA (1995) Effects of 3’ untranslated and intergenic regions on gene expression in Trypanosoma cruzi. Mol Biochem Parasitol 75:55–67

    CAS  PubMed  Google Scholar 

  • Ouaissi A, Cornette J, Taibi A et al (1988) Major surface immunogens of Trypanosoma cruzi trypomastigotes. Mem Inst Oswaldo Cruz 83(Suppl 1):502

    PubMed  Google Scholar 

  • Parodi AJ, Pollevick GD, Mautner M et al (1992) Identification of the gene(s) coding for the trans-sialidase of Trypanosoma cruzi. EMBO J 11:1705–1710

    CAS  PubMed  Google Scholar 

  • Paris G, Cremona ML, Amaya MF et al (2001) Probing molecular function of trypanosomal sialidases: single point mutations can change substrate specificity and increase hydrolytic activity. Glycobiology 11:305–311

    CAS  PubMed  Google Scholar 

  • Pereira-Chioccola VL, Acosta-Serrano A, Correia de Almeida I et al (2000) Mucin-like molecules form a negatively charged coat that protects Trypanosoma cruzi trypomastigotes from killing by human anti-alpha-galactosyl antibodies. J Cell Sci 113:1299–1307

    CAS  PubMed  Google Scholar 

  • Pierdominici-Sottile G, Roitberg AE (2011) Proton transfer facilitated by ligand binding. An energetic analysis of the catalytic mechanism of Trypanosoma cruzi trans-sialidase. Biochemistry 50:836–842

    CAS  PubMed  Google Scholar 

  • Pierdominici-Sottile G, Horenstein NA, Roitberg AE (2011) Free energy study of the catalytic mechanism of Trypanosoma cruzi trans-sialidase. From the michaelis complex to the covalent intermediate. Biochemistry 50:10150–10158

    CAS  PubMed  Google Scholar 

  • Piras MM, Henríquez D, Piras R (1987) The effect of fetuin and other sialoglycoproteins on the in vitro penetration of Trypanosoma cruzi trypomastigotes into fibroblastic cells. Mol Biochem Parasitol 22:135–143

    CAS  PubMed  Google Scholar 

  • Pitcovsky TA, Buscaglia CA, Mucci J, Campetella O (2002) A functional network of intramolecular cross-reacting epitopes delays the elicitation of neutralizing antibodies to Trypanosoma cruzi trans-sialidase. J Infect Dis 186:397–404

    CAS  PubMed  Google Scholar 

  • Pollevick GD, Affranchino JL, Frasch AC, Sanchez DO (1991) The complete sequence of a shed acute-phase antigen of Trypanosoma cruzi. Mol Biochem Parasitol 47:247–250

    CAS  PubMed  Google Scholar 

  • Previato JO, Andrade AF, Pessolani MC, Mendonça-Previato L (1985) Incorporation of sialic acid into Trypanosoma cruzi macromolecules. A proposal for a new metabolic route. Mol Biochem Parasitol 16:85–96

    CAS  PubMed  Google Scholar 

  • Previato JO, Jones C, Gonçalves LP et al (1994) O-glycosidically linked N-acetylglucosamine-boundoligosaccharides from glycoproteins of Trypanosoma cruzi. Biochem J 301:151–159

    CAS  PubMed  Google Scholar 

  • Previato JO, Jones C, Xavier MT et al (1995) Structural characterization of the major glycosylphosphatidylinositol membrane-anchored glycoprotein from epimastigote forms of Trypanosoma cruzi Y-strain. J Biol Chem 270:7241–7250

    CAS  PubMed  Google Scholar 

  • Priatel JJ, Chui D, Hiraoka N et al (2000) The ST3Gal-I sialyltransferase controls CD8+ T lymphocyte homeostasis by modulating O-glycan biosynthesis. Immunity 12:273–283

    CAS  PubMed  Google Scholar 

  • Reina-San-Martin B, Cosson A, Minoprio P (2000) Lymphocyte polyclonal activation: a pitfall for vaccine design against infectious agents. Parasitol Today 16:62–67

    CAS  PubMed  Google Scholar 

  • Ribeirão M, Pereira-Chioccola VL, Eichinger D et al (1997) Temperature differences for trans-glycosylation and hydrolysis reaction reveal an acceptor binding site in the catalytic mechanism of Trypanosoma cruzi trans-sialidase. Glycobiology 7:1237–1246

    PubMed  Google Scholar 

  • Risso MG, Pitcovsky TA, Caccuri RL et al (2007) Immune system pathogenesis is prevented by the neutralization of the systemic trans-sialidase from Trypanosoma cruzi during severe infections. Parasitology 134:503–510

    CAS  PubMed  Google Scholar 

  • Roggentin P, Rothe B, Kaper JB et al (1989) Conserved sequences in bacterial and viral sialidases. Glycoconj J 6:349–353

    Google Scholar 

  • Rosenberg I, Prioli RP, Ortega-Barria E, Pereira ME (1991) Stage-specific phospholipase C-mediated release of Trypanosoma cruzi neuraminidase. Mol Biochem Parasitol 46:303–305

    CAS  PubMed  Google Scholar 

  • Rubin-de-Celis SS, Uemura H, Yoshida N, Schenkman S (2006) Expression of trypomastigote trans-sialidase in metacyclic forms of Trypanosoma cruzi increases parasite escape from its parasitophorous vacuole. Cell Microbiol 8:1888–1898

    PubMed  Google Scholar 

  • Santana JM, Grellier P, Schrével J, Teixeira AR (1997) A Trypanosoma cruzi secreted 80 kDa proteinase with specificity for human collagen types I and IV. Biochem J 325:129–137

    CAS  PubMed  Google Scholar 

  • Sartor PA, Agusti R, Leguizamón MS et al (2010) Continuous nonradioactive method for screening trypanosomal trans-sialidase activity and its inhibitors. Glycobiology 20:982–990

    CAS  PubMed  Google Scholar 

  • Schauer R, Kamerling JP (2011) The chemistry and biology of trypanosomal trans-sialidases: virulence factors in chagas disease and sleeping sickness. Chembiochem 12:2246–2264

    CAS  PubMed  Google Scholar 

  • Schenkman S, Jiang MS, Hart GW, Nussenzweig V (1991) A novel cell surface trans-sialidase of Trypanosoma cruzi generates a stage-specific epitope required for invasion of mammalian cells. Cell 65:1117–1125

    CAS  PubMed  Google Scholar 

  • Schenkman S, Pontes-de-Carvalho L, Nussenzweig V (1992) Trypanosoma cruzi trans-sialidase and neuraminidase activities can be mediated by the same enzymes. J Exp Med 175:567–575

    CAS  PubMed  Google Scholar 

  • Scudder P, Doom JP, Chuenkova M et al (1993) Enzymatic characterization of beta-D-galactoside alpha 2,3-trans-sialidase from Trypanosoma cruzi. J Biol Chem 268:9886–9891

    CAS  PubMed  Google Scholar 

  • Sørensen AL, Rumjantseva V, Nayeb-Hashemi S et al (2009) Role of sialic acid for platelet life span: exposure of beta-galactose results in the rapid clearance of platelets from the circulation by asialoglycoprotein receptor-expressing liver macrophages and hepatocytes. Blood 114:1645–1654

    PubMed  Google Scholar 

  • Souza W, Carvalho TM, Barrias ES (2010) Review on Trypanosoma cruzi: host cell interaction. Int J Cell Biol 2010:1–18

    Google Scholar 

  • Staquicini DI, Martins RM, Macedo S et al (2010) Role of GP82 in the selective binding to gastric mucin during oral infection with Trypanosoma cruzi. PLoS Negl Trop Dis 4(3):e613

    PubMed  Google Scholar 

  • Taylor G (1996) Sialidases: structures, biological significance and therapeutic potential. Curr Opin Struct Biol 6:830–837

    CAS  PubMed  Google Scholar 

  • Todeschini AR, Mendonça-Previato L, Previato JO et al (2000) Trans-sialidase from Trypanosoma cruzi catalyzes sialoside hydrolysis with retention of configuration. Glycobiology 10:213–221

    CAS  PubMed  Google Scholar 

  • Todeschini AR, da-Silveira EX, Jones C et al (2001) Structure of O-glycosidically linked oligosaccharides from glycoproteins of Trypanosoma cruzi CL-brener strain: evidence for the presence of O-linked sialyl-oligosaccharides. Glycobiology 11:47–55

    CAS  PubMed  Google Scholar 

  • Todeschini AR, Girard MF, Wieruszeski JM et al (2002a) Trans-sialidase from Trypanosoma cruzi binds host T-lymphocytes in a lectin manner. J Biol Chem 277:45962–45968

    CAS  PubMed  Google Scholar 

  • Todeschini AR, Nunes MP, Pires RS et al (2002b) Costimulation of host T lymphocytes by a trypanosomal trans-sialidase: involvement of CD43 signaling. J Immunol 168:5192–5188

    CAS  PubMed  Google Scholar 

  • Todeschini AR, Dias WB, Girard MF et al (2004) Enzymatically inactive trans-sialidase from Trypanosoma cruzi binds sialyl and beta-galactopyranosyl residues in a sequential ordered mechanism. J Biol Chem 279:5323–5328

    CAS  PubMed  Google Scholar 

  • Todeschini AR, de Almeida EG, Agrellos OA et al (2009) Alpha-N -acetylglucosamine- linked O-glycans of sialoglycoproteins (Tc-mucins) from Trypanosoma cruzi colombiana strain. Mem Inst Oswaldo Cruz 104:270–274

    CAS  PubMed  Google Scholar 

  • Tomlinson S, Pontes-de-Carvalho LC, Vandekerckhove F, Nussenzweig V (1994) Role of sialic acid in the resistance of Trypanosoma cruzi trypomastigotes to complement. J Immunol 153:3141–3147

    CAS  PubMed  Google Scholar 

  • Tribulatti MV, Mucci J, Van Rooijen N et al (2005) The trans-sialidase from Trypanosoma cruzi induces thrombocytopenia during acute Chagas’ disease by reducing the platelet sialic acid contents. Infect Immun 73:201–207

    CAS  PubMed  Google Scholar 

  • Vandekerckhove F, Schenkman S, Pontes-de-Carvalho L et al (1992) Substrate specificity of the Trypanosoma cruzi trans-sialidase. Glycobiology 2:541–548

    CAS  PubMed  Google Scholar 

  • Varki A (2006) Nothing in glycobiology makes sense, except in the light of evolution. Cell 126:841–845

    CAS  PubMed  Google Scholar 

  • Varki A, Gagneux P (2012) Multifarious roles of sialic acids in immunity. Ann NY Acad Sci 1253:16–36

    CAS  PubMed  Google Scholar 

  • Vavricka CJ, Liu Y, Kiyota H et al (2013) Influenza neuraminidase operates via a nucleophilic mechanism and can be targeted by covalent inhibitors. Nat Commun 4:1491

    PubMed  Google Scholar 

  • Velge P, Ouaissi MA, Cornette J et al (1988) Identification and isolation of Trypanosoma cruzi trypomastigote collagen-binding proteins: possible role in cell-parasite interaction. Parasitology 97:255–268

    CAS  PubMed  Google Scholar 

  • Watts AG, Damager I, Amaya ML et al (2003) Trypanosoma cruzi trans-sialidase operates through a covalent sialyl-enzyme intermediate: tyrosine is the catalytic nucleophile. J Am Chem Soc 125:7532–7533

    CAS  PubMed  Google Scholar 

  • Weston D, La Flamme AC, Van Voorhis WC (1999) Expression of Trypanosoma cruzi surface antigen FL-160 is controlled by elements in the 3’ untranslated, the 3’ intergenic, and the coding regions. Mol Biochem Parasitol 102:53–66

    CAS  PubMed  Google Scholar 

  • Woronowicz A, De Vusser K, Laroy W et al (2004) Trypanosome trans-sialidase targets TrkA tyrosine kinase receptor and induces receptor internalization and activation. Glycobiology 14:987–998

    CAS  PubMed  Google Scholar 

  • Woronowicz A, Amith SR, Davis VW et al (2007) Trypanosome trans-sialidase mediates neuroprotection against oxidative stress, serum/glucose deprivation, and hypoxia-induced neurite retraction in Trk-expressing PC12 cells. Glycobiology 17:725–734

    CAS  PubMed  Google Scholar 

  • Yoshida N, Dorta ML, Ferreira AT et al (1997) Removal of sialic acid from mucin-like surface molecules of Trypanosoma cruzi metacyclic trypomastigotes enhances parasite-host cell interaction. Mol Biochem Parasitol 84:57–67

    CAS  PubMed  Google Scholar 

  • Yoshida N (2008) Trypanosoma cruzi infection by oral route: how the interplay between parasite and host components modulates infectivity. Parasitol Int 57:105–109

    CAS  PubMed  Google Scholar 

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Acknowledgments

The study was financially supported by Conselho Nacional de Desenvolvimento e Tecnologia (CNPq) Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior and the National Institute for Science and Technology in Vaccines (CNPq 573547/2008-4).

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Correspondence to Adriane R. Todeschini .

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Oliveira, I.A., Freire-de-Lima, L., Penha, L.L., Dias, W.B., Todeschini, A.R. (2014). Trypanosoma cruzi Trans-Sialidase: Structural Features and Biological Implications. In: Santos, A., Branquinha, M., d’Avila-Levy, C., Kneipp, L., Sodré, C. (eds) Proteins and Proteomics of Leishmania and Trypanosoma. Subcellular Biochemistry, vol 74. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7305-9_8

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