Oxidative stress: A boon or bane for trypanosomatids diseases?

Abstract

Infectious diseases are menace to the mankind, having a major contribution to the human morbidity and mortality. Trypanosomatids have a pervasive effect in the world, causing devastating but neglected diseases such as leishmaniasis, Chagas disease, and African sleeping sickness affecting 27 million people world-wide with 150,000 deaths annually. Trypanosomatids developing drug resistance is the current bottleneck in providing promising chemotherapeutics for these diseases which forces the continuous quest for new drugs and drug candidates. Balancing redox homeostasis is crucial for cell survival which has various implications in the biology of these parasites. Reactive oxygen species (ROS) act as signaling molecules, involving in various pathways and crucial for survival. Conversely, various chemotherapeutic drugs against trypanosomatids-caused ROS induction result in oxidative stress, eventually leading to apoptotic manifestations. Oxidative stress is one of the host defense mechanisms to control the infection, while detoxification is one of the crucial counteracts at the parasite front for successful host-parasite interaction. Therefore, oxidative stress is a good tool for better understanding of parasite biology, pathogenesis, and hostpathogen interactions. It is noteworthy that trypanosomatids have divergence from all other prokaryotes and eukaryotes at their redox system, majorly trypanothione-trypanothione reductase (TR)-based redox metabolism. The absence of this system in mammalians and structural/functional differences from host enzymes make it a lucrative target for studying its role in oxidative stress control and also to develop effective chemotherapeutics. One of the causes for drug resistance of trypanosomatids is due to their action of inducing oxidative stress which in turn activates repair mechanisms resulting in the development of drug resistance. Hence, studying oxidative stress mechanism of trypanosomatids gives insights into drug resistance, which is an impendence in attaining efficacious chemotherapy. In this chapter, we have tried to give an outline of the significance of redox stress and its role in different cellular metabolisms of trypanosomatids, with a special focus on trypanothione-trypanothione reductase (TR)-based redox system as a peculiar system to study trypanosomatids oxidative stress mechanism, also for drug designing.