Identification and characterization of iron transporters in the glycossomes of Leishmania

• Grant number: 19/21185-5
• Support Opportunities: Scholarships in Brazil - Master
• Start date: October 01, 2019
• End date: February 28, 2022
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Maria Fernanda Laranjeira da Silva
• Grantee: Romário Lopes Boy
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 17/23933-3 - Identification and characterization of membrane proteins involved in iron transport and metabolism in Leishmania, AP.JP

Abstract

Protozoa of the Leishmania genus are responsible for diseases generically known as leishmaniasis that affect humans worldwide. These organisms are parasites that alternate between the invertebrate and vertebrate host where they are able to survive and replicate in macrophages, despite the defense arsenal of these host cells, and from these cells the infection is propagated. One of the critical conditions found by Leishmania in the macrophage is the lack of nutrients, including iron, which is a cofactor of several enzymes essential for the parasite. The identification and study of genes essential for iron uptake by these parasites revealed that the availability of iron plays a central role in their virulence. These studies also demonstrated that iron deprivation induces the expression of a series of genes whose function is still unknown, generating an excellent opportunity for the identification of additional components of the molecular machinery involved in iron metabolism in these parasites.Trypanosomatids have unique organelles called glycosomes, which represent one of the major differences between parasite and host. These organelles compartmentalize the first seven enzymes involved in the glycolytic pathway, enzymes involved in fatty acid ²-oxidation, and also participate in antioxidant cellular processes. Iron-dependent superoxide dismutases (FeSOD) are particularly important enzymes as they play a role in protecting the parasite against free radicals resulting from NADPH oxidase activation, and Leishmania glycosomes compartmentalize the superoxide dismutase B isoforms (SODB1/2) that use only iron as cofactor. Several unsuccessful attempts to generate FeSODB knockouts have shown that this isoform is essential for Leishmania survival indicating that the unexplored transport of iron to the glycosome is also an interesting target for identification and study. Therefore, the aim of this project is to identify and characterize the genes involved in iron transport to Leishmania glycosome through the analysis of transcriptome data of iron-deprived parasites. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

BOY, Romário Lopes. Identification and characterization of candidate genes for iron transporters for the Leishmania amazonensis glycosome. 2022. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB) São Paulo.