Mediation of Trypanosoma cruzi invasion by sialic acid on the host cell and trans-sialidase on the trypanosome

Mao, Ming; Chuenkova, Marina V.; Ortega-Barrı́a, Eduardo; Pereira, M. E. A.

doi:10.1016/0166-6851(93)90222-j

Cited by 107 publications

(82 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Alternatively, the enzyme may sialylate host cell glycomolecules to generate receptors used by the trypanosome for adherence to and penetration of target cells. Results with sialic acid-deficient mutants of Chinese hamster ovary cells support this hypothesis (7)(8)(9). Sialic acid-deficient cells are less infected than wild type cells, suggesting that recognition of sialyl residues on Chinese hamster ovary cells is necessary during T. cruzi invasion.…”

mentioning

confidence: 89%

Enzymatically Inactive trans-Sialidase from Trypanosoma cruzi Binds Sialyl and β-Galactopyranosyl Residues in a Sequential Ordered Mechanism

Todeschini

Dias

Girard

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

Host/parasite interaction mediated by carbohydrate/ lectin recognition results in the attachment to and invasion of host cells and immunoregulation, enabling parasite replication and establishment of infection. Trypanosoma cruzi, the protozoan responsible for Chagas disease, expresses on its surface a family of enzymatically active and inactive trans-sialidases. The parasite uses the active trans-sialidase for glycoprotein sialylation in an unusual trans-glycosylation reaction. Inactive trans-sialidase is a sialic acid-binding lectin that costimulates host T cells through leucosialin (CD43) engagement. The co-mitogenic effect of trans-sialidase can be selectively abrogated by N-acetyllactosamine, suggesting the presence of an additional carbohydrate binding domain for galactosides, in addition to that for sialic acid. Here we investigated the interaction of inactive trans-sialidase in the presence of ␤-galactosides. By using NMR spectroscopy, we demonstrate that inactive trans-sialidase has a ␤-galactoside recognition site formed following a conformational switch induced by sialoside binding. Thus prior positioning of a sialyl residue is required for the ␤-galactoside interaction. When an appropriate sialic acid-containing molecule is available, both sialoside and ␤-galactoside are simultaneously accommodated in the inactive trans-sialidase binding pocket. This is the first report of a lectin recognizing two distinct ligands by a sequential ordered mechanism. This uncommon binding behavior may play an important role in several biological aspects of T. cruzi/host cell interaction and could shed more light into the catalytic mechanism of the sialic acid transfer reaction of enzymatically active trans-sialidase.Trypanosoma cruzi is the etiologic agent of Chagas disease or American trypanosomiasis that affects ϳ18 million people in Central and South America. Another 100 million people are at risk of infection (1). Mammalian cell invasion is crucial for T. cruzi survival (2). Elucidation of molecular components regulating the initiation of the parasitic infection is critical for understanding the pathogenesis of Chagas disease and will enable the development of novel, effective, and selective treatments.Initial communication between T. cruzi trypomastigotes and mammalian cells requires contact of soluble or membranebound parasite molecules with host ligands. T. cruzi expresses on its surface a family of glycosylphosphatidylinositol-anchored active and inactive trans-sialidase (TS) 1 proteins (3-5), which contain a Tyr or a His residue, respectively, at position 342 (4). The parasite uses active TS to sialylate its surface glycoproteins by a trans-sialidase reaction (6). Thus, TS activity is capable of extensively remodeling the T. cruzi cell surface by using host glycoconjugates as sialyl donor. Alternatively, the enzyme may sialylate host cell glycomolecules to generate receptors used by the trypanosome for adherence to and penetration of target cells. Results with sialic acid-deficient mutants of Chinese hamster ov...

show abstract

mentioning

confidence: 89%

Enzymatically Inactive trans-Sialidase from Trypanosoma cruzi Binds Sialyl and β-Galactopyranosyl Residues in a Sequential Ordered Mechanism

Todeschini

Dias

Girard

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…TS is present both on the T. cruzi outer membrane and in the extracellular milieu as a soluble factor and, thus, is strategically located to promote trypanosome-host-cell interaction (28,29), cytokine secretion, and cell survival. Indeed, TS as well as its recombinant catalytic domain cTS (residues 33-666 of TS sequence, GenBank accession no.…”

Section: Ts Through Cts Is a Specific Survival Factor For Schwann Cmentioning

confidence: 99%

Trypanosoma cruzitrans-sialidase: A potent and specific survival factor for human Schwann cells by means of phosphatidylinositol 3-kinase/Akt signaling

Chuenkova

Furnari

Cavenee

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…These surface antigens are a highly polymorphic family of proteins with molecular masses ranging from 85 to 200 kDa. Many of these proteins have been implicated in a number of biological processes important for T. cruzi interaction with host cells and extra-cellular matrix proteins (6)(7)(8)(9)(10)(11). One group of these proteins are enzymes denominated transsialidase (TS) that catalyze the transfer of sialic acid to ß-galactosyl residues of mucinlike glycoproteins that are present on the surface of T. cruzi trypomastigotes and epimastigotes (12,13).…”

Section: Structure Of the Trans-sialidasementioning

confidence: 99%

“…However, there are suggestions that the transfer of sialic acid present on the surface of the host cell to the parasite may help trypomastigote adhesion and penetration into nonphagocytic cells (9,14). Sialic acid also provides a strongly negatively charged cover that protects parasites against human lytic antibodies specific for a-galactosyl residues which are abundant on the trypomastigote surface (Pereira-Chiccola VL, Acosta-Serrano A, Almeida I, Rodrigues MM, Travassos LR and Schenkman S, unpublished results).…”

Section: Structure Of the Trans-sialidasementioning

confidence: 99%

Trans-sialidase delivered as a naked DNA vaccine elicits an immunological response similar to a Trypanosoma cruzi infection

Costa

Pereira-Chioccola

Ribeirão

et al. 1999

Braz J Med Biol Res

View full text Add to dashboard Cite

Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, does not synthesize sialic acid, but expresses a trans-sialidase (TS) that catalyzes the transfer of sialic acid from host glycoconjugates to the parasite surface. Here, we review studies that characterize the immune response to the catalytic domain of the enzyme in humans during Chagas disease or in mice following immunization with the TS gene. In both cases, there are antibodies that strongly inhibit the enzymatic activity and generation of interferon-g-producing T cells.

show abstract

Mediation of Trypanosoma cruzi invasion by sialic acid on the host cell and trans-sialidase on the trypanosome

Cited by 107 publications

References 19 publications

Enzymatically Inactive trans-Sialidase from Trypanosoma cruzi Binds Sialyl and β-Galactopyranosyl Residues in a Sequential Ordered Mechanism

Enzymatically Inactive trans-Sialidase from Trypanosoma cruzi Binds Sialyl and β-Galactopyranosyl Residues in a Sequential Ordered Mechanism

Trypanosoma cruzitrans-sialidase: A potent and specific survival factor for human Schwann cells by means of phosphatidylinositol 3-kinase/Akt signaling

Trans-sialidase delivered as a naked DNA vaccine elicits an immunological response similar to a Trypanosoma cruzi infection

Contact Info

Product

Resources

About