The Complex World of Cellular Defense in the Leishmania Parasite

Abstract

Reactive oxygen species (ROS) and their products are the main agents used by cells to kill invading pathogens. Therefore, to establish a successful infection, pathogens require a robust defensive system to counteract host-generated oxidative stress and their products. Leishmania parasites with a digenetic life cycle, cause Kala-azar and are exposed to conditions of moderate to severe oxidative stress in both the insect and the mammalian hosts. Natural selection has endowed these parasites with multiple defense systems including a peroxiredoxin system of defense, a robust system of thiols, arginases, ascorbate peroxidases, kinases and phophatases, all of which can be used for thwarting potential threats. In addition to these, the parasites are able to defend themselves by altering the host defense mechanisms through the manipulation of host cytokines and other signaling pathways. The peroxiredoxin system is distinct from mammalian peroxiredoxin system and absence of the parasite components in the mammalian host makes them potential drug targets. Trypanothione, a thiol unique to the Leishmania parasite, serves as a central molecule for a cascade of enzymes through which the electrons are shuffled and finally used by the terminal enzyme, the tryparedoxin peroxidase (TXNPx) to eliminate peroxides. Tryapanothione can directly interact with the products of the oxidative stress and can be formed from cellular glutahione. This review discusses the relevance of the parasite defense systems in the context of cell death in the Leishmania parasites.