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

MARÍA DE LOS MILAGROS CAMARA; BALOUZ, VIRGINIA; CENTENO CAMEÁN, CAMILA; CORI, CARMEN R.; KASHIWAGI, GUSTAVO A.; GIL, SANTIAGO A.; GUAIMAS, FRANCISCO; LOBO, MAITE MABEL; DE LEDERKREMER, ROSA M.; GALLO -RODRIGUEZ, CAROLA; BUSCAGLIA, CARLOS A.

CABA

Congreso; 3rd Argentinian Symposium on Glycobiology; 2019

GlycoAr

Chagas disease, caused by the protozoan Trypanosoma cruzi, is a life-long and debilitating neglected illness of major significance to Latin America public health, for which no vaccine or adequate drugs are yet available. In this scenario, identification of novel drug targets and/or strategies aimed at controlling parasite transmission are urgently needed. By using ex vivo binding assays together with different biochemical and genetic approaches, we herein show that Gp35/50 kDa mucins, the major T. cruzi epimastigote surface glycoproteins, specifically adhere to the internal cuticle of the rectal ampoule of the triatomine vector, a critical step leading to their differentiation into mammal-infective metacyclic forms. Ex vivo binding assays in the presence of chemically synthesized analogs allowed the identification of a solvent-exposed peptide and a branched, galactofuranose (Galf)-containing trisaccharide (Galfb1-4[Galpb1-6]GlcNAca) from their O-linked glycans as Gp35/50 kDa mucins adhesion determinants. Overall, these results provide novel insights into the mechanisms underlying the complex T. cruzi triatomine interplay. In addition, and since the presence of Galf based glycotopes on the O-glycans of 68 Gp35/50 kDa mucins isrestricted to certain parasite strains, they also indicate that the Galfb1-4[Galpb1- 6]GlcNAca motif may contribute to T. cruzi phenotypic variability. Most importantly, and taking into account that Galf residues are not found in mammals, we propose Gp35/50 kDa mucins and/or Galf biosynthesis as appealing and novel targets for the development of T. cruzi transmission-blockingstrategies.