FUNCTIONAL CHARACTERIZATION OF T. CRUZI MUCINS IN THE INFECTION OF THE INSECT

CAMARA MARIA DE LOS MILAGROS; CAMILA CENTENO CAMEAN; BALOUZ, VIRGINIA; LOBO MAITE MABEL; BUSCAGLIA, CARLOS A.

Mar del Plata

Congreso; Reunion Anual de Biociencias; 2019

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. In this work using a genetic and a biochemical approach we functionally characterised the role of T. cruzi surface mucins in the infection of the invertebrate host. 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 thetriatomine 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 theidentification of a solvent-exposed peptide and a branched, galactofuranose (Galf)-containing trisaccharide (Galfß1-4[Galpß1-6]GlcNAcAlpha) from their O-linked glycans as Gp35/50 kDa mucins adhesion determinants. Furthermore in vivo infection assays revealed that parasites overexpressing Gp35/50 KDa mucins presented a higher infectivity in the insect host which was also correlated with a higher number of metacyclic forms in the rectal ampoule in comparison with control lines. Overall, these results provide novel insights into the mechanisms underlying the complex T. cruzi triatomine interplay. 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-blocking strategies.