Trypanosoma cruzi surface mucins are involved in the attachment to the Triatoma infestans rectal ampoule
| Autor: | Carola Gallo-Rodriguez, Rosa M. de Lederkremer, Virginia Balouz, Gustavo A. Kashiwagi, Camila Centeno Camean, Marta Victoria Cardinal, Natalia Paula Macchiaverna, Carlos A. Buscaglia, Francisco Fernando Guaimas, María de los Milagros Camara, Santiago A. Gil, Carmen R. Cori, Maite Mabel Lobo |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Life Cycles RC955-962 Protozoan Proteins Protozoology Disease Vectors Biochemistry 0302 clinical medicine Arctic medicine. Tropical medicine Medicine and Health Sciences Parasite hosting Triatoma chemistry.chemical_classification Protozoans biology Chemistry Eukaryota Hindgut Insects Infectious Diseases Epimastigotes Protozoan Life Cycles Public aspects of medicine RA1-1270 Anatomy Research Article Chagas disease Glycan Trypanosoma Arthropoda Trypanosoma cruzi 030231 tropical medicine Research and Analysis Methods Microbiology 03 medical and health sciences Triatoma infestans medicine Parasitic Diseases Animals Humans Chagas Disease Molecular Biology Techniques Molecular Biology Mucin Public Health Environmental and Occupational Health Mucins Rectum Organisms Biology and Life Sciences Proteins biology.organism_classification medicine.disease Invertebrates Parasitic Protozoans Insect Vectors Gastrointestinal Tract Species Interactions 030104 developmental biology biology.protein Glycoprotein Digestive System Developmental Biology Cloning |
| Zdroj: | PLoS Neglected Tropical Diseases PLoS Neglected Tropical Diseases, Vol 13, Iss 5, p e0007418 (2019) |
| ISSN: | 1935-2735 |
| Popis: | 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, Galf-containing trisaccharide (Galfβ1–4[Galpβ1–6]GlcNAcα) from their O-linked glycans were identified as main adhesion determinants for these molecules. Interestingly, exogenous addition of a synthetic Galfβ1–4[Galpβ1–6]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 Galf 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 Galf biosynthetic pathway, which is absent in mammals and insects, as appealing targets for the development of T. cruzi transmission-blocking strategies. Author summary 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. 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 the triatomine 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 the identification of a solvent-exposed peptide and a branched, galactofuranose (Galf)-containing trisaccharide (Galfβ1–4[Galpβ1–6]GlcNAcα) as major Gp35/50 kDa mucins adhesion determinants. Overall, these results provide novel insights into the mechanisms underlying the complex T. cruzi-triatomine interplay. In addition, and since the presence of Galf-based glycotopes on the O-glycans of Gp35/50 kDa mucins is restricted to certain parasite strains/clones, they also indicate that the Galfβ1–4[Galpβ1–6]GlcNAcα motif may 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 targets for the development of T. cruzi transmission-blocking strategies. |
| Databáze: | OpenAIRE |
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