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

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

PLOS NEGLECTED TROPICAL DISEASES

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2019 vol. 13 p. 1 - 23

1935-2735

Chagas disease, caused by the protozoan Trypanosoma cruzi, is a life-long and debilitatingneglected 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. Byusing 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 triatominevector, a critical step leading to their differentiation into mammal-infective metacyclicforms. Ex vivo binding assays in the presence of chemically synthesized analogs allowedthe identification of a solvent-exposed peptide and a branched, galactofuranose (Galf)-containing trisaccharide (Galfβ1?4[Galpβ1?6]GlcNAcα) as major Gp35/50 kDa mucinsadhesion determinants. Overall, these results provide novel insights into the mechanismsunderlying the complex T. cruzi-triatomine interplay. In addition, and since the presenceof Galf-based glycotopes on the O-glycans of Gp35/50 kDa mucins is restricted to certainparasite strains/clones, they also indicate that the Galfβ1?4[Galpβ1?6]GlcNAcα motifmay contribute to the well-established phenotypic variability among T. cruzi isolates.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 targetsfor the development of T. cruzi transmission-blocking strategies