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

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

San Martin, Provincia de Buenos Aires

Simposio; 3º Argentinian Symposium on Glycobiology; 2019

Chagas disease, caused by the protozoan Trypanosoma cruzi, isa life-long and debilitating neglected illness of major significance toLatin America public he alth, f or whi ch n o v accine or a dequatedrugs 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 k Da muc ins, t he ma jor T. cr uzi epimastigote surfaceglycoproteins, specifically adhere to the internal cuticle of the rectalampoule of t he t riatomine vector, a c ritical s tep leading to t heirdifferentiation in to m ammal-infective m etacyclic fo rms. E x v ivobinding assays in the presence of chemically synthesized analogsallowed the identification of a s olvent-exposed p eptide an d abranched, galactofuranose (Galf)-containing trisaccharide (Galfȕ1-4[Galpȕ1-6]GlcNAcÁ) from their O-linked glycans as Gp35/50 kDamucins a dhesion d eterminants. Ov erall, t hese r esults pr ovidenovel insights into the mechanisms underlying the complex T. cruzitriatomine interplay. In addition, and s ince the presence of Galf-based glycotopes on the O-glycans of 68 Gp35/50 kDa mucins isrestricted to c ertain parasite s trains, t hey al so i ndicate t hat t heGalfȕ1-4[Galpȕ1- 6] GlcNAcÁ m otif m ay c ontribute to T. c ruziphenotypic variability. Most importantly, and taking into accountthat Galf residues are not found in mammals, we propose Gp35/50kDa m ucins a nd/or G alf bi osynthesis as a ppealing a nd noveltargets f or t he d evelopment of T. c ruzi t ransmission-blockingstrategies.