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

Abstract

Background Trypanosoma cruzi , the agent of Chagas disease, is a protozoan parasite transmitted to humans by blood-sucking triatomine vectors. However, and despite its utmost biological and epidemiological relevance, T . cruzi development inside the digestive tract of the insect remains a poorly understood process. Methods/Principle findings Here we showed that Gp35/50 kDa mucins, the major surface glycoproteins from T . cruzi insect-dwelling forms, are involved in parasite attachment to the internal cuticle of the triatomine rectal ampoule, a critical step leading to its differentiation into mammal-infective forms. Experimental evidence supporting this conclusion could be summarized as follows: i) native and recombinant Gp35/50 kDa mucins directly interacted with hindgut tissues from Triatoma infestans , as assessed by indirect immunofluorescence assays; ii) transgenic epimastigotes over-expressing Gp35/50 kDa mucins on their surface coat exhibited improved attachment rates (~2–3 fold) to such tissues as compared to appropriate transgenic controls and/or wild-type counterparts; and iii) certain chemically synthesized compounds derived from Gp35/50 kDa mucins were able to specifically interfere with epimastigote attachment to the inner lining of T . infestans rectal ampoules in ex vivo binding assays, most likely by competing with or directly blocking insect receptor(s). A solvent-exposed peptide (smugS peptide) from the Gp35/50 kDa mucins protein scaffolds and a branched, Gal f -containing trisaccharide (Gal f β1–4[Gal p β1–6]GlcNAcα) from their O -linked glycans were identified as main adhesion determinants for these molecules. Interestingly, exogenous addition of a synthetic Gal f β1–4[Gal p β1–6]GlcNAcα derivative or of oligosaccharides containing this structure impaired the attachment of Dm28c but not of CL Brener epimastigotes to triatomine hindgut tissues; which correlates with the presence of Gal f residues on the Gp35/50 kDa mucins’ O -glycans on the former but not the latter parasite clone. Conclusion/Significance These results provide novel insights into the mechanisms underlying T . cruzi- triatomine interplay, and indicate that inter-strain variations in the O -glycosylation of Gp35/50 kDa mucins may lead to differences in parasite differentiation and hence, in parasite transmissibility to the mammalian host. Most importantly, our findings point to Gp35/50 kDa mucins and/or the Gal f ...

Engineering a single-chain antibody against Trypanosoma cruzi metacyclic trypomastigotes to block cell invasion

“…cruzi metacyclics. Our results in combination with published by Camara et al [50] show the great potential of using scFv-10D8 in paratransgenesis approach in a format similar to that used for T . brucei , either alone or in combination with lytic peptides to interfere with parasite::insect interaction.…”

“…Camara et al [50] have reported that gp35/50 is a key molecule required for parasite attachment to the internal cuticle of the triatomine rectal ampoule, thus affecting epimastigote to metacyclic trypomastigotes differentiation. These author suggest that targeting gp35/50 is appealing mechanism to block parasite transmission.…”

Mucins and Pathogenic Mucin-Like Molecules Are Immunomodulators During Infection and Targets for Diagnostics and Vaccines

“…Sialylation may also reduce the susceptibility of the parasite to anti-α-Gal antibodies present in the mammalian bloodstream (Pereira-Chioccola et al, 2000), allowing colonization and infection. Recently, T. cruzi mucins were also associated with parasite attachment to the internal cuticle of the triatomine rectal ampoule, a critical step leading to T. cruzi differentiation into infective forms to mammalian host cells (Cámara et al, 2019).…”

An Update on the Knowledge of Parasite–Vector Interactions of Chagas Disease

“… 84 Also, surface mucins of T. cruzi seem to be involved in the attachment, but Gp35/50 kDa mucins cover the whole body of the epimastigotes, not only the small hydrophobic region. 85 …”