Mucin-like molecules form a negatively charged coat that protects Trypanosoma cruzi trypomastigotes from killing by human anti-alpha-galactosyl antibodies

Mucin-like molecules form a negatively charged coat that protects Trypanosoma cruzi trypomastigotes from killing by human anti-alpha-galactosyl antibodies

Author Pereira-Chioccola, V. L. Google Scholar
Acosta-Serrano, A. Google Scholar
Almeida, I. C. de Google Scholar
Ferguson, MAJ Google Scholar
Souto-Padron, T. Google Scholar
Rodrigues, Mauricio Martins Autor UNIFESP Google Scholar
Travassos, Luiz Rodolpho Autor UNIFESP Google Scholar
Schenkman, Sergio Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Inst Dante Pazzanese Cardiol Estado Sao Paulo
Johns Hopkins Univ
Univ Dundee
Universidade Federal do Rio de Janeiro (UFRJ)
Abstract In the presence of sialic acid donors Trypanosoma cruzi acquires up to 10(7) sialic acid residues on its surface, in a reaction catalyzed by its unique trans-sialidase. Most of these sialic acid residues are incorporated into mucin-like glycoproteins. To further understand the biological role of parasite sialylation, we have measured the amount of mucin in this parasite, We found that both epimastigote and trypomastigote forms have the same number of mucin molecules per surface area, although trypomastigotes have less than 10% of the amount of glycoinositol phospholipids, the other major surface glycoconjugate of T. cruzi, Based on the estimated surface area of each mucin, we calculated that these molecules form a coat covering the entire trypomastigote cell, The presence of the surface coat is shown by transmission electron microscopy of Ruthenium Red-stained parasites, The coat was revealed by binding of antibodies isolated from Chagasic patients that react with high affinity to a-galactosyl epitopes present in the mucin molecule, When added to the trypomastigote, these antibodies cause an extensive structural perturbation of the parasite coat with formation of large blebs, ultimately leading to parasite lysis, Interestingly, lysis is decreased if the mucin coat is heavily sialylated, Furthermore, addition of MgCl2 reverses the protective effect of sialylation, suggesting that the sialic acid negative charges stabilize the surface coat, Inhibition of sialylation by anti-trans-sialidase antibodies, found in immunized animals, or human Chagasic sera, also increase killing by anti-a-galactosyl antibodies, Therefore, the large amounts of sialylated mucins, forming a surface coat on infective trypomastigote forms, have an important structural and protective role.
Keywords Trypanosoma cruzi
trans-sialidase
surface coat
antibodies
alpha-galactosyl
Language English
Date 2000-04-01
Published in Journal Of Cell Science. Cambridge: Company Of Biologists Ltd, v. 113, n. 7, p. 1299-1307, 2000.
ISSN 0021-9533 (Sherpa/Romeo, impact factor)
Publisher Company Of Biologists Ltd
Extent 1299-1307
Origin http://jcs.biologists.org/content/113/7/1299
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000086855400020
URI http://repositorio.unifesp.br/11600/44232

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