Recent issues of the biochemistry and molecular biology of Trypanosoma cruzi

Abstract

Recent issues of the biochemistry and molecular biology of Trypanosoma cruzi investigated by prestigious Brazilian research groups and discussed in the present meeting in commemoration of the 90th anniversary of the recognition of Chagas disease, center on glycoconjugates, their structure and function; differential gene expression in developmental stages of the parasite; organization and expression of multigene families encoding virulence factors; and the epidemiology, biochemistry and evolution of different strains of the parasite using rRNA sequences.Almeida and coworkers have studied the complex structure of mucin-like glycoproteins from infective forms of T. cruzi and advanced in the knowledge of their immunological properties. These molecules are densely packed over the entire surface of trypomastigotes and contain O-glycosidically-linked oligosaccharides which are terminally substituted by numerous sialic acid units. Many of the biological properties of these GPIanchored mucins have been related to the presence of these acidic residues. Two major features of T. cruzi mucins emerged from studies by different groups: (a) in contrast with mammalian mucins, the O-linked oligosaccharide chains of T. cruzi mucins are bound via an internal unit of Nacetylglucosamine; (b) sialic acid units are added to the oligosaccharide chains via a trans-sialidase reaction which uses sialylated donors from the medium. Mucins from epimastigotes and metacyclic forms differ from those of cell culture trypomastigotes in their apparent molecular mass, susceptibility to proteolysis and fine glycosidic structure. They also show peculiar characteristics in the lipidic moiety of the GPI anchors which are related with some of their immunological properties. A striking feature of the infective trypomastigote mucins is the presence of terminal α-galactopyranosyl units in their oligosaccharides which are targets of lytic antibodies isolated from patients with chronic Chagas disease. It is highly relevant that the successful chemotherapy in some chagasic patients can be monitored by the gradual decrease in the lytic antibody titers. These antibodies are now being detected by extremely sensitive chemiluminescent Elisa using very small amounts of purified trypomastigote mucins. Recent studies showed that trypomastigote mucins, but not those from epimastigotes or metacyclic forms potently induce the synthesis by stimulated macrophages of proinflammatory cytokines (IL-12 and TNF-α) and of nitric oxide. Since these effects are obtained using extremely reduced amounts of mucins they appear to have physiological relevance in vivo especially since mucins may be shed into the medium by T. cruzi infective forms. A most careful study is presently being carried out by Almeida et al. to correlate minimum structural requirements with immunobiological activity using powerful methods of purification and characterization of the mucins and their GPI moieties. The precise role of these components of T. cruzi in the pathophysiology of experimental and human inf...