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Taxonomic group: protista / Euglenozoa (Phylum: Euglenozoa)
Host organism: (mammals)
Organ / tissue: Life stage: trypomastigote
Associated disease: Chagas disease [ICD11: 1F53

, ICD11: XN56V

]; infection due to Trypanosoma cruzi [ICD11: XN56V

]

NCBI PubMed ID: 38198982
Publication DOI: 10.1016/j.carres.2023.109015
Journal NLM ID: 0043535
Publisher: Elsevier
Correspondence: I.C. Almeida <icalmeida

utep.edu>; K. Michael <kmichael

utep.edu>
Institutions: Department of Chemistry and Biochemistry, Border Biomedical Research Center, University of Texas at El Paso, 500 West University Avenue, El Paso, TX, 79968, USA, Department of Biological Sciences, Border Biomedical Research Center, University of Texas at El Paso, 500 West University Avenue, El Paso, TX, 79968, USA, Universidad Mayor de San Simón, Faculty of Medicine, and Fundación CEADES, Cochabamba, Bolivia, Universidad Nacional de Salta (UNSa)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Patología Experimental, Facultad de Ciencias de la Salud, Universidad Nacional de Salta, Salta, Argentina

The protozoan parasite Leishmania (Viannia) braziliensis is among Latin America's most widespread Leishmania species and is responsible for tegumentary leishmaniasis (TL). This disease has multiple clinical presentations, with cutaneous leishmaniasis (CL) being the most frequent. It manifests as one or a few localized skin ulcers, which can spread to other body areas. Hence, early diagnosis and treatment, typically with pentavalent antimonials, is critical. Traditional diagnostic methods, like parasite culture, microscopy, or the polymerase chain reaction (PCR) for detection of the parasite DNA, have limitations due to the uneven distribution of parasites in biopsy samples. Nonetheless, studies have revealed high levels of parasite-specific anti-α-Gal antibodies in L. (V.) braziliensis-infected patients. Previously, we demonstrated that the neoglycoprotein NGP28b, consisting of the L. (Leishmania) major type-2 glycoinositolphospholipid (GIPL)-3-derived trisaccharide Galpα1,6Galpα1,3Galfβ conjugated to bovine serum albumin (BSA) via a linker, acts as a reliable serological biomarker (BMK) for L. (V.) braziliensis infection in Brazil. This indicates the presence of GIPL-3 or a similar structure in this parasite, and its terminal trisaccharide either functions as or is part of an immunodominant glycotope. Here, we explored whether extending the trisaccharide with a mannose unit would enhance its efficacy as a biomarker for the serological detection of L. (V.) braziliensis. We synthesized the tetrasaccharide Galpα1,6Galpα1,3Galfβ1,3Manpα(CH2)3SH (G31SH) and conjugated it to maleimide-functionalized BSA to afford NGP31b. When we assessed the efficacy of NGP28b and NGP31b by chemiluminescent enzyme-linked immunosorbent assay on a cohort of CL patients with L. (V.) braziliensis infection from Bolivia and Argentina against a healthy control group, both NGPs exhibited similar or identical sensitivity, specificity, and accuracy. This finding implies that the mannose moiety at the reducing end is not part of the glycotope recognized by the parasite-specific anti-α-Gal antibodies in patients' sera, nor does it exert a relevant influence on the terminal trisaccharide's conformation. Moreover, the mannose does not seem to inhibit glycan-antibody interactions. Therefore, NGP31b is a viable and dependable BMK for the serodiagnosis of CL caused by L. (V.) braziliensis.

antibodies, oligosaccharide synthesis, neoglycoprotein, Biomarker, chemiluminescent enzyme-linked immunosorbent assay, anti-alpha-Gal antibody, Leishmania (Viannia) braziliensis

Structure type: fragment of a bigger structure
Location inside paper: p. 109015-2
Aglycon: GPI-anchored mucin-like glycoproteins (tGPI-MUC)
Trivial name: α-gal epitope, tGPI-MUC
Contained glycoepitopes: IEDB_115013,IEDB_130645,IEDB_130649,IEDB_135815,IEDB_136044,IEDB_136906,IEDB_137340,IEDB_137472,IEDB_140108,IEDB_141496,IEDB_141794,IEDB_141807,IEDB_149558,IEDB_151528,IEDB_151531,IEDB_190606,IEDB_418918,IEDB_918314,SB_165,SB_166,SB_187,SB_195,SB_30,SB_7,SB_87,SB_88

Methods: 13C NMR, 1H NMR, PCR, TLC, ELISA, chemical synthesis, MALDI-TOF MS, glycosylation, CC, conjugation, HR-ESI-MS
Comments, role: the terminal glycan moiety of GPI

Related record ID(s): 15611, 15614, 15615, 15616
NCBI Taxonomy refs (TaxIDs): 5693
Show glycosyltransferases

There is only one chemically distinct structure:

CC(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O[C@@H]2O[C@H](CO)[C@H](O)[C@H](O[C@H]3O[C@H](CO)[C@H](O)[C@H](O)[C@H]3O)[C@H]2O)[C@@H]1O

SVG MW SMILES 3D mol Ionize