Parasite-host glycan interactions during Trypanosoma cruzi infection: trans-Sialidase rides the show

Abstract

Many important pathogen-host interactions rely on highly specific carbohydrate binding events. In the case of the protozoan Trypanosoma cruzi, the causative agent of Chagas disease, glycointeractions involving sialic acid (SA) residues are pivotal for parasite infectivity, escape from immune surveillance and pathogenesis. Though unable to synthesize SA de novo, T. cruzi displays a unique trans-Sialidase (TS) enzyme, which is able to cleave terminal SA residues from host donor glycoconjugates and transfer them onto parasite surface mucins, thus generating protective/adhesive structures. In addition, this parasite sheds TS into the bloodstream, as a way of modifying the surface SA signature, and thereby the signaling/functional properties of mammalian host target cells on its own advantage. Here, we discuss the pathogenic aspects of T. cruzi TS: its molecular adaptations, the multiplicity of interactions in which it is involved during infections, and the array of novel and appealing targets for intervention in Chagas disease provided by TS-remodeled sialoglycophenotypes.

Keywords: Chagas disease; Glycobiology of infection; Pathogenesis; Sialic acids; Trypanosoma cruzi; trans-Sialidase.

FIGURE 1:

Possible evolution of trans-Sialidase genes in T. cruzi.

FIGURE 2:. Structural and biological features of molecules belonging to the Group I of T. cruzi Gp85/trans-Sialidases.

Schematic representation of predicted TS molecules expressed by trypomastigote (TS and iTS, above) and epimastigote (eTS, below) forms of T. cruzi. For trypomastigote TS, identity of residue 342 discriminates between enzymatically active TS (Tyr) and inactive iTS (His) molecules. The position of predicted signal peptide, membrane-anchoring sequence, and typical bacterial sialidase motifs (Asp-boxes, FR[I/D]P tetrapeptide) is indicated. The sequences of the adhesive FLY motif (VTVxNVxLYNR, where x means any amino acid) and of a typical SAPA repeat (DSSAHGTPSTPV) are also shown. (?) means that the nature of the eTS membrane anchor has not been yet experimentally addressed. For trypomastigote TS molecules, the major biological effects of the N-terminal, catalytic region and of the SAPA repeats are indicated below. The structure of the catalytic region of TS, showing the presence of two independent domains (the catalytic one and a lectin-like one) connected by a α-helix is shown in the inset. GPI, glycosylphosphatidylinositol.