Trypanosoma cruzi heparin-binding proteins and the nature of the host cell heparan sulfate-binding domain

• Published in: Microbial pathogenesis 2008-04, Vol.44 (4), p.329-338
• Main Authors: Oliveira, Francisco Odencio Rodrigues de, Alves, Carlos Roberto, Calvet, Cláudia Magalhães, Toma, Leny, Bouças, Rodrigo Ippolito, Nader, Helena Bociani, Castro Côrtes, Luzia Monteiro de, Krieger, Marco Aurélio, Meirelles, Maria de Nazareth S.L., Souza Pereira, Mirian Claudia de
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cardiomyocytes; Cells, Cultured; Cercopithecus aethiops; Chlorates - pharmacology; Chromatography; Chromatography, Affinity; Fundamental and applied biological sciences. Psychology; Glycosaminoglycans; Heparan Sulfate Proteoglycans - metabolism; Heparin - metabolism; Heparin - pharmacology; Life cycle. Host-agent relationship. Pathogenesis; Mice; Molecular Weight; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - parasitology; Protein Binding - drug effects; Protein Structure, Tertiary; Protozoa; Protozoan Proteins - chemistry; Protozoan Proteins - isolation & purification; Protozoan Proteins - metabolism; Recognition process; Trypanosoma cruzi; Trypanosoma cruzi - drug effects; Trypanosoma cruzi - metabolism; Vero Cells
• ISSN: 0882-4010; 1096-1208
• DOI: 10.1016/j.micpath.2007.10.003

Trypanosoma cruzi invasion is mediated by receptor–ligand recognition between the surfaces of both parasite and target cell. We have previously demonstrated the role of heparan sulfate proteoglycan in the attachment and invasion of T. cruzi in cardiomyocytes. Herein, we have isolated the T. cruzi heparin-binding proteins (HBP-Tc) and investigated the nature of cardiomyocyte heparan sulfate (HS)-binding site to the parasite surface ligand. Two major heparin-binding proteins with molecular masses of 65.8 and 59 kDa were observed in total extract of amastigote and trypomastigote forms of T. cruzi. Hydrophobic [S 35]methionine labeled proteins eluted from heparin–sepharose affinity chromatography also revealed both proteins in trypomastigotes but only the 59 kDa is strongly recognized by biotin-conjugated glycosaminoglycans. Competition assays were performed to analyze the role of sulfated proteoglycans, including heparin, keratan sulfate and both acetylated and highly sulfated domains of heparan sulfate, in the recognition and invasion process of T. cruzi. Significant inhibitions of 84% and 35% in the percentage of infection were revealed after treatment of the parasites with heparin and the N-acetylated/ N-sulfated heparan sulfate domain, respectively, suggesting the important role of the glycuronic acid and NS glucosamine domain of the HS chain in the recognition of the HBP-Tc during the T. cruzi–cardiomyocyte interaction.