Proteomic and Bioinformatic Analysis of Trypanosoma cruzi Chemotherapy and Potential Drug Targets: New Pieces for an Old Puzzle
Rubem Figueiredo Sadok Menna-Barreto, Kele Teixeira Belloze, Jonas Perales and Floriano Paes Silva-Jr
Affiliation: Laboratorio de Bioquimica de Proteinas e Peptideos, Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil 4365 – 21040-360, Manguinhos, Rio de Janeiro, Brazil.
Chagas disease is endemic in Latin America and is caused by the protozoan hemoflagellate parasite Trypanosoma
cruzi. Nowadays, it has also been disseminated to non-endemic countries due to the ease of global mobility. The nitroheterocycle
benznidazole is currently used to treat this neglected tropical disease, although this drug causes severe side
effects and has limited efficacy during the chronic phase of the disease. Proteomics and bioinformatics have recently become
powerful tools in the identification of new drug targets. In the last decade, proteomic profiles of different T. cruzi
forms under distinct experimental conditions were assessed. These reports have pointed to many potential drug targets,
with ergosterol biosynthesis-related proteins and redox system enzymes being the most promising candidates. Nevertheless,
the majority of the compounds active against T. cruzi still have unclear mechanisms of action, and most proteomic
efforts have studied epimastigotes (the non-clinically relevant insect form of the parasite). Additional analyses with the
clinically relevant parasite forms should be performed to identify proteins that actually bind drugs active against T. cruzi.
Nonetheless, due to the known technical hurdles in generating such experimental data, bioinformatic approaches that integrate
currently available data to generate additional knowledge will also be useful. Here, we review T. cruzi proteomics
and describe the main chemoproteomic methods and their application to the identification of trypanosomatid drug targets.
Finally, we discuss the potential benefits of more extensively integrating all proteomic data with other molecular databases
via bioinformatic analyses to develop novel, viable strategies for alternative treatments of Chagas disease.
Keywords: Bioinformatics, chagas disease, chemotherapy, (chemo) proteomics, drug targets, Trypanosoma cruzi.
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