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

dc.contributor.authorPereira-Chioccola, V. L.
dc.contributor.authorAcosta-Serrano, A.
dc.contributor.authorAlmeida, I. C. de
dc.contributor.authorFerguson, MAJ
dc.contributor.authorSouto-Padron, T.
dc.contributor.authorRodrigues, Mauricio Martins [UNIFESP]
dc.contributor.authorTravassos, Luiz Rodolpho [UNIFESP]
dc.contributor.authorSchenkman, Sergio [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionInst Dante Pazzanese Cardiol Estado Sao Paulo
dc.contributor.institutionJohns Hopkins Univ
dc.contributor.institutionUniv Dundee
dc.contributor.institutionUniversidade Federal do Rio de Janeiro (UFRJ)
dc.description.abstractIn 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.en
dc.description.affiliationUNIFESP, Dept Microbiol Imunol & Parasitol, BR-04023062 Sao Paulo, Brazil
dc.description.affiliationInst Dante Pazzanese Cardiol Estado Sao Paulo, Lab Xenodiag, BR-0401280 Sao Paulo, Brazil
dc.description.affiliationJohns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA
dc.description.affiliationUniv Dundee, Dept Biochem, Dundee DD1 5EH, Scotland
dc.description.affiliationUFRJ, Inst Biofis, BR-21949900 Rio De Janeiro, Brazil
dc.description.affiliationUnifespUNIFESP, Dept Microbiol Imunol & Parasitol, BR-04023062 Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.identifier.citationJournal Of Cell Science. Cambridge: Company Of Biologists Ltd, v. 113, n. 7, p. 1299-1307, 2000.
dc.publisherCompany Of Biologists Ltd
dc.relation.ispartofJournal Of Cell Science
dc.rightsAcesso aberto
dc.subjectTrypanosoma cruzien
dc.subjectsurface coaten
dc.titleMucin-like molecules form a negatively charged coat that protects Trypanosoma cruzi trypomastigotes from killing by human anti-alpha-galactosyl antibodiesen