The Glycan Structure of T. cruzi mucins Depends on the Host. Insights on the Chameleonic Galactose

Abstract

Trypanosoma cruzi, the protozoa that causes Chagas disease in humans, is transmitted by insects from the Reduviidae family. The parasite has developed the ability to change the structure of the surface molecules, depending on the host. Among them, the mucins are the most abundant glycoproteins. Structural studies have focused on the epimastigotes and metacyclic trypomastigotes that colonize the insect, and on the mammal trypomastigotes. The carbohydrate in the mucins fulfills crucial functions, the most important of which being the accepting of sialic acid from the host, a process catalyzed by the unique parasite trans-sialidase. The sialylation of the parasite influences the immune response on infection. The O-linked sugars have characteristics that differentiate them from human mucins. One of them is the linkage to the polypeptide chain by the hexosamine, GlcNAc, instead of GalNAc. The main monosaccharide in the mucins oligosaccharides is galactose, and this may be present in three configurations. Whereas β-d-galactopyranose (β-Galp) was found in the insect and the human stages of Trypanosoma cruzi, β-d-galactofuranose (β-Galf) is present only in the mucins of some strains of epimastigotes and α-d-galactopyranose (α-Galp) characterizes the mucins of the bloodstream trypomastigotes. The two last configurations confer high antigenic properties. In this review we discuss the different structures found and we pose the questions that still need investigation on the exchange of the configurations of galactose.

Overview of paratransgenesis as a strategy to control pathogen transmission by insect vectors

“…Regarding recombinant β-glucanase as an effector molecule in paratransgenesis, the surface of T. cruzi is covered in a layer of mucin-like glycoproteins that are probably essential for the in vivo development of the parasite by mediating its binding to the triatomine midgut and hindgut cells [ 258 , 259 ]. Jose et al [ 256 ] concluded that disruption of the surface glycocalyx of T. cruzi would therefore inhibit the development of the parasite.…”

Specific Recognition of β-Galactofuranose-Containing Glycans of Synthetic Neoglycoproteins by Sera of Chronic Chagas Disease Patients

“…Previous studies have shown that the sera of CCD patients contain not only anti-α-Gal Abs, but also anti-β-Galf Abs [18,20,32]. The major molecular targets of anti-β-Galf Abs in CD are most likely protein-free GIPLs and β-Galf -containing O-glycans on GPI-anchored glycoproteins (e.g., mucins) of the infective insect-vector-derived metacyclic trypomastigote (Meta) and mammal-dwelling TCT forms [20,26,27,[33][34][35]. Moreover, given that all T. cruzi glycoprotein GPI moieties and GIPLs described so far are based on the (Manα1,2)Manα1,2Manα1,6Manα1,4GlcNα1,6PI structure [25][26][27]29,34,[36][37][38][39], one of several possible TCT-derived GPI-anchor structures is proposed in Figure 1.…”

Interaction With the Extracellular Matrix Triggers Calcium Signaling in Trypanosoma cruzi Prior to Cell Invasion

“…The invasion of host mammalian cells by T. cruzi trypomastigotes is a complex process which requires distinct surface molecules, and the activation of multiple signaling pathways in the parasites, as well as in the host cells ( De Souza et al., 2010 ; Caradonna and Burleigh, 2011 ; Maeda et al., 2012 ; Giorgi and de Lederkremer, 2020 ; Nájera et al., 2021 ). Molecules from the parasite surface, such as members of the gp85/Transialidase glycoproteins coded by a multigenic family, bind to the ECM components, as a first step of the invasion process ( Alves and Colli, 2008 ; De Souza et al., 2010 ; Nde et al., 2012 ), which triggers relevant changes in phosphorylation, S-nitrosylation, and nitration levels of proteins in T. cruzi trypomastigotes, Y strain, which elicit a reprogramming of the parasite metabolism ( Mattos et al., 2019 ) or modification of the DNA binding profile of nitrated histones ( Magalhães et al., 2020 ).…”