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Study of the regulation of iron and heme transporters at the Leishmania-host interface: effect of iron deficiency anemia on the virulence of Leishmania (L.) amazonensis

Grant number: 21/03355-0
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): September 01, 2021
Effective date (End): July 31, 2022
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Principal researcher:Maria Fernanda Laranjeira da Silva
Grantee:Ahyun Hong
Home 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

Leishmaniases, a spectrum of diseases caused by protozoan parasites of the genus Leishmania, affect millions of people around the world. During infection, nutrients availability within the parasitophorous vacuoles is known to have significant effects on parasite replication and virulence. This process requires the acquisition of essential nutrients such as iron and heme from the host since Leishmania does not have iron storage proteins and does not have heme biosynthesis capacity. Besides, iron and heme can be cytotoxic as they trigger the generation of free radicals in the presence of oxygen. Leishmania, therefore, must acquire heme and iron to survive in a hostile environment that restricts the availability of nutrients to the pathogen, a process called nutritional immunity. Identification of several proteins that participate in the transport of iron and heme was crucial for understanding these metabolic pathways in Leishmania, and the loss of an allele or both alleles of those transporters cause serious defects in the differentiation and/or multiplication of these parasites in the host. The goal of this project is to investigate the cross-regulation between iron and heme transporters, LIT1 and LHR1, and whether Leishmania growth and virulence are inextricably dependent on the host's iron and heme levels, elucidating the significance of the host's iron and heme status in the progression of Leishmania infection. This project will allow a better understanding of the mechanisms of Leishmania-host interaction focused on the pathways of iron and heme metabolism at the cellular and systemic level. (AU)

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