Trypanosoma cruzi surface mucins are involved in the attachment to the Triatoma infestans rectal ampoule

CÁMARA, MARÍA DE LOS MILAGROS; CORI, CR; GUAIMAS, F; GALLO-RODRÍGUEZ; CAMEAN, CAMILA CENTENO; GIL, S; DE LEDERKREMER, ROSA M.; BALOUZ VIRGINIA; KASHIWAGI, G; LOBO, MAITE; BUSCAGLIA, CARLOS A.

Simposio; 3rd Argentinian Symposium on Glycobiology (GlycoAR2019); 2019

UNSAM

Chagas disease, caused by the protozoan Trypanosoma cruzi, isa life-long and debilitating neglected illness of major significance toLatin America public health, for which no vaccine or adequatedrugs are yet available. In this scenario, identification of novel drugtargets and/or strategies aimed at controlling parasite transmissionare urgently needed. By using ex vivo binding assays together withdifferent biochemical and genetic approaches, we herein show thatGp35/50 kDa mucins, the major T. cruzi epimastigote surfaceglycoproteins, specifically adhere to the internal cuticle of the rectalampoule of the triatomine vector, a critical step leading to theirdifferentiation into mammal-infective metacyclic forms. Ex vivobinding assays in the presence of chemically synthesized analogsallowed the identification of a solvent-exposed peptide and abranched, galactofuranose (Galf)-containing trisaccharide (Galfβ1-4[Galpβ1-6]GlcNAcα) from their O-linked glycans as Gp35/50 kDamucins adhesion determinants. Overall, these results providenovel insights into the mechanisms underlying the complex T. cruzitriatomine interplay. In addition, and since the presence of Galfbased glycotopes on the O-glycans of 68 Gp35/50 kDa mucins isrestricted to certain parasite strains, they also indicate that theGalfβ1-4[Galpβ1- 6]GlcNAcα motif may contribute to T. cruziphenotypic variability. Most importantly, and taking into accountthat Galf residues are not found in mammals, we propose Gp35/50kDa mucins and/or Galf biosynthesis as appealing and noveltargets for the development of T. cruzi transmission-blockingstrategies.