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

• Grant number: 17/23933-3
• Support type: Research Grants - Young Investigators Grants
• Duration: September 01, 2018 - October 31, 2023
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal researcher: Maria Fernanda Laranjeira da Silva
• Grantee: Maria Fernanda Laranjeira da Silva
• Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Assoc. researchers: Juliana Ide Aoki ; Lucile Maria Floeter-Winter
• Associated scholarship(s): 21/03355-0 - 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, BP.DD; 19/21185-5 - Identification and characterization of iron transporters in the glycossomes of Leishmania, BP.MS; 19/03861-3 - Study of the cross-regulation between transport of iron and heme mediated by LIT1 and LHR1 in Leishmania, BP.MS; 19/09715-9 - Characterization of manganese transport mediated by the iron transporter LIR1 in Leishmania, BP.IC; 18/15971-5 - Identification and characterization of membrane proteins involved in iron transport and metabolism in Leishmania., BP.JP

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)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

AOKI, JULIANA IDE; LARANJEIRA-SILVA, MARIA FERNANDA; MUXEL, SANDRA MARCIA; FLOETER-WINTER, LUCILE MARIA. The impact of arginase activity on virulence factors of Leishmania amazonensis. Current Opinion in Microbiology, v. 52, p. 110-115, DEC 2019. (17/23933-3, 14/50717-1, 16/03273-6, 16/19815-2)

AOKI, JULIANA IDE; HONG, AHYUN; ZAMPIERI, RICARDO ANDRADE; FLOETER-WINTER, LUCILE MARIA; LARANJEIRA-SILVA, MARIA FERNANDA. In Vivo Infection with Leishmania amazonensis to Evaluate Parasite Virulence in Mice. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, n. 156, FEB 2020. (17/23933-3)

LARANJEIRA-SILVA, MARIA FERNANDA; HAMZA, IQBAL; PEREZ-VICTORIA, JOSE M.. Iron and Heme Metabolism at the Leishmania-Host Interface. Trends in Parasitology, v. 36, n. 3, p. 279-289, MAR 2020. (17/23933-3)

HONG, AHYUN; ZAMPIERI, RICARDO ANDRADE; SHAW, JEFFREY JON; FLOETER-WINTER, LUCILE MARIA; LARANJEIRA-SILVA, MARIA FERNANDA. One Health Approach to Leishmaniases: Understanding the Disease Dynamics through Diagnostic Tools. PATHOGENS, v. 9, n. 10, OCT 2020. (17/23933-3, 18/23512-0)