Preliminary 1H NMR investigation of sialic acid transfer by the trans-sialidase from Trypanosoma cruzi

Wilson, Jennifer C.; Kiefel, Milton J.; Albouz-Abo, Samia; Itzstein, Mark von

doi:10.1016/s0960-894x(00)00572-2

Cited by 10 publications

(2 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is accomplished by the trans ‐sialidase (TS), a unique enzyme of T. cruzi . This enzyme cleaves sialic acid from host glycoconjugates and transfers it to acceptor structures on the surface of the parasite (Vandekerckhove et al ., 1992; Colli, 1993; Schenkman et al ., 1994; Frasch, 2000; Wilson et al ., 2000; Buschiazzo et al ., 2002). Sialylation of T. cruzi was shown to confer resistance to human complement, which is a prerequisite for infection (Tomlinson et al ., 1994).…”

Section: Introductionmentioning

confidence: 99%

Sialylated ligands on pathogenicTrypanosoma cruziinteract with Siglec-E (sialic acid-binding Ig-like lectin-E)

Erdmann¹,

Steeg²,

Koch-Nolte³

et al. 2009

Cellular Microbiology

View full text Add to dashboard Cite

SummaryTrypanosoma cruzi causes a suppression of the immune system leading to persistence in host cells. The trans-sialidase expressed by T. cruzi is a major virulence factor and transfers sialic acid from host glycoconjugates to mucin-like molecules on the parasite. Here we demonstrate that these sialylated structures play a role in the immunosuppression. We used two T. cruzi strains, whose TS activity correlated with their pathogenicity. The Tulahuen strain, characterized by a high TS activity efficiently infected mice, whereas the Tehuantepec strain showing a reduced TS activity could not establish a patent parasitemia. In vitro analysis revealed that these two strains invaded phagocytic and non-phagocytic host cells at a comparable rate, but they exhibited different potentials to modulate dendritic cell function. In contrast to Tehuantepec, the Tulahuen strain suppressed the production of the proinflammatory cytokine IL-12 and subsequent T-cell activation. This inhibitory effect was absent upon desialylation of the parasite. Therefore, we analysed whether sialylated structures of T. cruzi interact with the inhibitory sialic acid-binding protein Siglec-E on DC. Indeed, Siglec-E interacted with the pathogenic Tulahuen strain, but showed a diminished binding to the Tehuantepec strain. Ligation of Siglec-E on DC using antibodies confirmed this inhibitory effect on DC function.

show abstract

Section: Introductionmentioning

confidence: 99%

Sialylated ligands on pathogenicTrypanosoma cruziinteract with Siglec-E (sialic acid-binding Ig-like lectin-E)

Erdmann¹,

Steeg²,

Koch-Nolte³

et al. 2009

Cellular Microbiology

View full text Add to dashboard Cite

show abstract

“…We have had a longstanding interest [1][2][3] in the sialic acid family of carbohydrates, as well as sialic acid recognising proteins (SARPS), particularly enzymes, that are involved in their biosynthesis and degradation, and NMR spectroscopic methods for the investigation of enzymecatalysed reactions [4,5]. It is well known that nucleotide synthetases are essential for the biosynthesis of activated carbohydrates, commonly referred to as glycosyl donors.…”

Section: Introductionmentioning

confidence: 99%

A 1H STD NMR spectroscopic investigation of sialylnucleoside mimetics as probes of CMP-Kdn synthetase

et al. 2006

Self Cite

View full text Add to dashboard Cite

CMP-Kdn synthetase catalyses the reaction of sialic acids (Sia) and CTP to the corresponding activated sugar nucleotide CMP-Sia and pyrophosphate PP( i ). Saturation Transfer Difference (STD) NMR spectroscopy has been employed to investigate the sub-structural requirements of the enzyme's binding domain. Sialylnucleoside mimetics, where the sialic acid moiety has been replaced by a carboxyl group and a hydrophobic moiety, have been used in NMR experiments, to probe the tolerance of the CMP-Kdn synthetase to such replacements. From our data it would appear that unlike another sialylnucleotide-recognising protein, the CMP-Neu5Ac transport protein, either a phosphate group or other functional groups on the sialic acid framework may play important roles in recognition by the synthetase.

show abstract

The Chemistry and Biology of Trypanosomal trans‐Sialidases: Virulence Factors in Chagas Disease and Sleeping Sickness

Schauer

Kamerling

2011

ChemBioChem

View full text Add to dashboard Cite

trans-Sialidases constitute a special group of the sialidase family. They occur in some trypanosome species and, in a unique reversible reaction, transfer sialic acids from one glycosidic linkage with galactose (donor) to another galactose (acceptor), to form (α2-3)-sialyl linkages. Trypanosomes cause such devastating human diseases as Chagas disease in South America (Trypanosoma cruzi) or sleeping sickness in Africa (Trypanosoma brucei). The trans-sialidases strongly contribute to the pathogenicity of the trypanosomes by scavenging sialic acids from the host or blood meal to coat the parasite surface; this aids their survival strategy in the insect's intestine, and in the blood circulation or cells of the host, and serves to compromise the immune system of the human or animal host. American and African trypanosomes express trans-sialidases at different stages of their vector/host development. They are transmitted to humans by insect vectors (tsetse fly or other insect "bug" species). trans-Sialidase activity with varying linkage specificity has also been found in a few bacteria species and in human serum. trans-Sialidases are of increasing practical importance for the chemo-enzymatic synthesis of sialylated glycans. The search for appropriate inhibitors of trans-sialidases and vaccination strategies is intensifying, as less toxic medicaments for the treatment of these widespread and often chronic tropical diseases are required.

show abstract

Preliminary 1H NMR investigation of sialic acid transfer by the trans-sialidase from Trypanosoma cruzi

Cited by 10 publications

References 23 publications

Sialylated ligands on pathogenicTrypanosoma cruziinteract with Siglec-E (sialic acid-binding Ig-like lectin-E)

Sialylated ligands on pathogenicTrypanosoma cruziinteract with Siglec-E (sialic acid-binding Ig-like lectin-E)

A 1H STD NMR spectroscopic investigation of sialylnucleoside mimetics as probes of CMP-Kdn synthetase

The Chemistry and Biology of Trypanosomal trans‐Sialidases: Virulence Factors in Chagas Disease and Sleeping Sickness

Contact Info

Product

Resources

About