Date of Award

2020-01-01

Degree Name

Doctor of Philosophy

Department

Biological Sciences

Advisor(s)

Igor C. Almeida

Abstract

Trypanosoma cruzi, the causative agent of Chagas disease (CD) currently affects 6-7 million people across the world. Currently, only two drugs, benznidazole and nifurtimox, are available for treatment of CD and they are highly toxic and less effective in the chronic stage of the disease. Specific biomarkers for diagnosis and follow-up of treatment do not exist in the clinical settings. following chemotherapy, patients take approximately 10-20 years to exhibit negative seroconversion with the conventional serology assays. Moreover, there is no vaccine available to prevent or treat CD. T. cruzi contains a complex cell surface consisting of several classes of glycoconjugates anchored by a glycosylphosphatidylinositol (GPI) post-translational modification. One of these GPI-anchored glycoconjugates are the GPI-mucins, which exist abundantly and serve important protective roles in both vector- and mammal-dwelling developmental stages of the parasite. GPI-Mucin polypeptide cores are heavily modified by O- glycans. In the infective trypomastigote stage, terminal a-galactopyranosyl (α-Gal) glycotopes are highly abundant and serve as primary targets for protective IgG anti-a-Gal antibodies. Here, we show the evaluation of α-Gal-containing neoglycoproteins (α-Gal- NGPs), whose glycan moieties are based on mammalian cell-derived trypomastigote GPI-mucin (tGPI-mucin) O-glycans, as potential biomarkers for diagnosis and early assessment of chemotherapeutic outcomes of CD. Finally, we also performed glycomic analysis of epimastigote-derived GPI-mucin O-glycans, aiming to establish the methodology to characterize novel glycotopes for use as biomarkers for CD diagnosis, chemotherapy follow-up, and vaccine development.

Language

en

Provenance

Received from ProQuest

File Size

116 pages

File Format

application/pdf

Rights Holder

Uriel Ortega Rodriguez

Download

Share

COinS