Molecular characterization of Trypanosoma cruzi and shed vesicle components involved in host immunomodulation and cell invasion
Chagas disease caused by Trypanosoma cruzi is a devastating infectious disease with millions of cases in Latin America, and recently became a public health concern in United States and Europe. Although many efforts have been made for the development of an effective immunotherapy, currently there is no human vaccine for Chagas disease. Thus, the treatment is based only on two drugs that have limited efficacy and in some cases present severe side effects. One restriction for the rational approach to develop new therapies against this disease is the limited information about the proteins, glycolipids and protein posttranslational modifications expressed by different phylogenetic lineages, strains, and stages of the parasite. In this dissertation, I focused in the analysis of glycoconjugates of the T. cruzi surface and secreted vesicles, as well in the analysis of the parasite phosphoproteome. The results presented here demonstrated that the glycocalix of each stage of the parasite has major differences in the composition. The cell surface of the insect stages of the parasite is mainly composed by a highly diverse glycolipid coat, in addition to short highly glycosylated polypeptides. On the other hand, the surface coat of mammalian host-dwelling stages is composed mainly by hundreds of glycoproteins. These findings have many implications for the parasite survival in the insect and mammalian hosts. Next, by examining the phosphoproteins of the epimastigote stage of the parasite, over 200 phosphorylation sites were mapped in proteins with various functions. Taken together, the results from this dissertation brought new insights into T. cruzi physiology and virulence, which may have implications for the design of new therapies against Chagas disease.^
Biology, Molecular|Biology, Microbiology|Biology, Parasitology
Nakayasu, Ernesto Satoshi, "Molecular characterization of Trypanosoma cruzi and shed vesicle components involved in host immunomodulation and cell invasion" (2008). ETD Collection for University of Texas, El Paso. AAI3341650.