Functional characterization of Trypanosoma cruzi surface mucins in the infection of the invertebrate host

BALOUZ VIRGINIA; LOBO, MAITE MABEL; BUSCAGLIA, CARLOS A.; CAMEAN, CAMILA CENTENO; DE LEDERKREMER, ROSA M.; CÁMARA, MARÍA DE LOS MILAGROS; CORI, CARMEN R.; GALLO-RODRIGUEZ, CAROLA

Woods Hole

Congreso; XXX Molecular Parasitology Meeting; 2019

Chagas disease, caused by the protozoan Trypanosoma cruzi, is a life-long and debilitating neglected illness of major significance to LatinAmerica public health, for which no vaccine or adequate drugs are yetavailable. In this scenario, identification of novel drug targets and/orstrategies aimed at controlling parasite transmission are urgentlyneeded. In this work using a genetic and a biochemical approach wefunctionally characterised the role of T. cruzi surface mucins in theinfection of the invertebrate host. By using ex vivo binding assaystogether with different biochemical and genetic approaches, we hereinshow that Gp35/50 kDa mucins, the major T. cruzi epimastigote surfaceglycoproteins, specifically adhere to the internal cuticle of the rectalampoule of the triatomine vector ( T. infestans and R. prolixus), a criticalstep leading to their differentiation into mammal-infective metacyclicforms. Ex vivo binding assays in the presence of chemicallysynthesized analogs allowed the identification of a solvent-exposedpeptide and a branched, galactofuranose (Galf)-containingtrisaccharide (Galfβ1-4[Galpβ1-6]GlcNAcα) from their O-linked glycansas Gp35/50 kDa mucins adhesion determinants. Furthermore in vivoinfection assays in R. prolixus revealed that parasites overexpressingGp35/50 KDa mucins presented a higher infectivity in the insect hostwhich was also correlated with a higher number of metacyclic forms inthe rectal ampoule in comparison with control lines. Overall, theseresults provide novel insights into the mechanisms underlying thecomplex T. cruzi triatomine interplay. Most importantly, and taking intoaccount that Galf residues are not found in mammals, we proposeGp35/50 kDa mucins and/or Galf biosynthesis as appealing and noveltargets for the development of T. cruzi transmission-blockingstrategies.