XI International Meeting on Paracoccidioidomycosis

XI International Meeting on Paracoccidioidomycosis

Resume:165-1

Investigação

165-1	Lessons from distant relatives: systems biology of kinetoplastids as a model for discovery of therapeutic targets in pathogenic fungi
Authors:	Igor C. Almeida (UTEP - University of Texas at El Paso)

Abstract

Pathogenic kinetoplastids, such as the protozoan parasites Trypanosoma cruzi and Trypanosoma brucei, are responsible for major infectious diseases, namely Chagas disease (CD) and human African trypanosomiasis (HAT), which affect millions of people worldwide and cause thousands of deaths and significant economic losses in developing countries. Current drugs for treating these diseases are partially effective and highly toxic, and vaccines are not available. Thus, there is an urgent need for the discovery of molecular targets for the development of new chemo- and immunotherapeutic interventions. In this regard, our group and several collaborators have been developing novel systems biology (omics) approaches and adapting established ones (e.g., proteomics, lipidomics, glycomics) for the global analysis of proteins, lipids, glycolipids, and co-/post-translational modifications (CTMs/PTMs) (e.g., glycosylation, GPI-anchoring, phosphorylation, SUMOylation, and palmitoylation) of T. cruzi and T. brucei. Proteomic analysis of infective life-cycle stages of T. cruzi has led to the discovery of hundreds of potential CD8 T cell epitopes. The top peptide candidates are currently being tested in vitro and in vivo as T cell-based vaccines for experimental CD. In addition, glycan array analysis of protective antibodies from patients against glycans exclusively expressed by the parasite (as determined by glycomics) has resulted in the discovery and validation of a highly effective carbohydrate-based vaccine for experimental CD. Moreover, we have recently carried out SUMOproteomics, phosphoproteomics, and GPIomics of T. cruzi and identified numerous potential molecular targets, which are now being validated. Regarding T. brucei, we have recently analyzed the global palmitoylproteome of the parasite and found several potential drug targets, which are currently being validated as well. Systems biology (omics) approaches are becoming increasingly vital molecular tools for the discovery and validation of drug and vaccine targets in kinetoplastids. Considering that protozoan parasites and fungi share many common traits regarding their metabolism and pathophysiological mechanisms, here we will discuss how we can exploit these approaches for the discovery of new therapeutic targets and interventions against pathogenic fungi, including Paracoccidioides brasiliensis. Support: NIH grants 1R01AI070655, 3R01AI070655-04S1, 2SO6GM00812, 2G12RR008124-16A1, and 2G12RR008124-16A1S1.

Keyword: Systems Biology, Omics, Kinetoplastids, Fungi, Drug and vaccine development

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