Identification and characterization of membrane proteins involved in iron transport and metabolism in Leishmania

Abstract

Protozoan parasites of the genus Leishmania are responsible for diseases generally known as leishmaniasis that affect millions of humans around the world. These organisms are digenetic parasites that during the intracellular phase of their life cycle are called amastigotes. The amastigote form inhabits the parasitoforous vacuoles of the mammalian macrophages. The processes leading to the differentiation of the promastigote form, found in the insect vector, to the amastigote form are the subject of many studies, since the amastigotes are able to survive and replicate inside macrophages despite their cell defense arsenal. One of the conditions found by Leishmania in the macrophage is the lack of nutrients such as iron, which is the cofactor of several enzymes essential for Leshmania. The identification and study of genes related to the transport of iron by these parasites revealed that the availability of iron plays a central role in the generation of infective parasites. Iron deprivation modulates the expression of several non-characterized genes, providing an excellent opportunity for the identification of additional components of the molecular machinery responsible for iron acquisition, storage and metabolism in these parasites. Thus, this project aims to identify and characterize new genes involved in the transport and metabolism of iron, and potentially other transition metals, in Leishmania through the analysis of transcriptome data of iron-deprived parasites. Identification of the pathways related to iron transport and metabolism is central for understanding the physiology of these parasites and the interaction of this parasite with its hosts, besides pointing novel therapeutic targets that can potentially help in the development of better chemotherapies against leishmaniasis. (AU)