Glycoproteins on T. cruzi’s Surface

In the parasite Trypanosoma cruzi, mucin‑like glycoproteins play an important role in the organism’s interaction with the surface of the mammalian cell during the invasion process (Di Noia, Sánchez, and Frasch 1995). Mucins are highly glycosylated proteins expressed by most secretory epithelial tissues in vertebrates; but recent research has shown that these geneencoding molecules have been detected in Leishmania major (Murray and Spithill 1991) and in Trypanosoma cruzi (Reyes, Pollevick, and Frasch 1994). These mucin‑like genes have a defined basic structure and sequence, which allows their inclusion in a gene family.

Trypanosoma cruzi has a family of putative mucin genes whose organization resembles the ones present in mammalian cells (Di Noia, Sánchez, and Frasch 1995). Different parasite isolates have different sets of genes, as defined by their central domain. Much work has been done on the biochemical and functional characterization of mucin‑like surface glycoconjugates (Schenkman et al. 1994). These heavily O‑glycosylated molecules are Thr‑, Ser‑, and Pro‑rich and are attached to a membrane by a glycophosphatidylinositol anchor (Schenkman et al. 1993). Mucins in T. cruzi are the major acceptors of sialic acid in a reaction catalyzed by trans‑sialidase. These molecules are involved in the cell‑invasion process, probably mediating adhesion of the parasite to the mammalian cell surface (Ruiz et al. 1993, Yoshida et al. 1989). A putative mucin gene in T. cruzi has been identified (Reyes et al. 1994), having a small size and encoding five repeat units with the consensus sequence T₈KP₂. In a later study, Di Noia, Sànchez, and Frasch (1995) establish that T. cruzi does in fact have a putative mucin gene family resembling the one present in vertebrate cells. Their members have a Thr/Ser/Pro‑rich central domain, which might or might not be organized in repetitive units, and highly conserved non‑repetitive flanking domains.

In earlier studies (e.g., Snary 1985:144‑48), the following glycoprotein or antigens have been found on T. cruzi’s surface. Lipopeptido phosphoglycan (LPPG) is a complex surface component found on the membrane of epimastigotes. This large complex molecule includes three glycoproteins with a molecular weight (MW) of 37,000, 31,000, and 24,000 (referred to as GP‑37, GP‑31, and GP‑24, respectively). Indirect evidence indicates that LPPG may also be found on amastigotes, because antibodies against LPPG have been found in the serum of patients with Chagas’ disease. Generally, epimastigotes are thought to occur only in insects and not in the vertebrate host, although this conclusion is not definitive. The presence of LPPG antibodies in hosts apparently indicates that this glycoprotein is also found on trypanosomes in the host. It is not clear why the current reasoning is that it is found on amastigotes alone and not also on trypomastigotes.

The function of LPPG in T. cruzi is not known, but it is postulated that it provides some protection for free‑living protozoa from the macroenvironment. Epimastigotes face an environment in the insect’s gut with many hostile components. LPPG, then, may be part of the baggage still carried by T. cruzi from among the characteristics displayed by free‑living ancestors of the parasite. Once the ancestors of American trypanosomes gave up their free‑living life‑style, perhaps they kept LPPG because it came in handy inside the insect’s gut. In other words, it was a pre‑adaptive feature allowing them to settle in what would otherwise be a hostile environment.

Glycoprotein (GP‑90) is another cell‑surface antigen found on all three life‑cycle forms‑trypomastigote, epimastigote, and amastigote. One parasite‑promoting function of GP‑90 is that it interferes with complement‑mediated lysis of the parasite. Antibodies to GP‑90 are found in all patients, and these antibodies do not cross‑react with leishmaniasis antigens. Consequently, GP90 shows great promise as a diagnostic tool to differentiate between Chagas’ disease and leishmaniasis in Bolivia, where patients are subject to infection from T. cruzi and from Leishmania sp. and where diagnostic testing frequently does not discriminate between them.

Another useful glycoprotein, GP‑72 (MW 72,000) is specific for epimastigote and metacyclic trypomastigote (infective parasites) insect stages, but it is not found on blood trypomastigotes or intracellular amastigotes. GP‑72 is very useful for isolating different strains (zymodemes) of T. cruzi, because each strain shows a different concentration ofGP‑72the higher the concentration of GP‑72, the more pathogenic the strain. Moreover, different strains of the parasite cause different clinical syndromes: some strains tend to megavisceralize and cause megasyndromes; others might concentrate in the heart and nerves.