Metabolomic profiling for the identification of drug targets in trypanosomes

Abstract

Trypanosomes belong to a group of unicellular flagellated eukaryotes which include species responsible for serious, potentially fatal human diseases, mainly occurring in tropical and subtropical regions of the world: Trypanosoma brucei for sleeping sickness in Africa, Trypanosoma cruzi for Chagas disease in the Americas. These parasitic protists are transmitted between people and susceptible animals by insects. Adequate treatment of the diseases remains an issue. In recent decades, progress has been made in developing new medication for human African trypanosomiasis, and in the elimination of the disease by improved surveillance and combating the tsetse fly vector. However, the possibility remains that the disease flares up when the public health situation will be under stress, as has happened in the past, as well as that trypanosomes will develop resistance against available drugs. The situation for American trypanosomiasis is even considerably more serious; the number of infected people is high, and there is a need for new safe, adequate treatment, since differently from African trypanosomiasis, current therapies are unsatisfactory. In this paper, we review the so far published studies in which metabolomic profiling has been used for the identification of the target(s) and mode of action of several available trypanocidal drugs as well as compounds currently in the drug discovery pipeline for treatment of trypanosomiasis.