Identification of phospholipid translocators in Leishmania

• Grant number: 14/17542-3
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: December 01, 2014
• End date: September 27, 2017
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Lucile Maria Floeter-Winter
• Grantee: Carolina de Lima Jorge
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The protozoa of the genus Leishmania have developed an escape strategy called apoptotic mimicry to evade the vertebrate host immune response. Of key importance in the silent entry into the vertebrate macrophage are lipid surface components. However, little is known about the composition and dynamics of membrane lipids in this parasite.The aim of this project is to identify the specific phospholipid(s) and the membrane translocator(s) responsible for their cell surface signaling that lead the macrophage to perform parasite phagocytosis without triggering an inflammatory response. To achieve our goals, we will generate L. (L.) amazonensis mutants overexpressing genes for candidate lipid transporters and regulators. The ability in binding of annexin V - a protein with high affinity with anionic phospholipids - to those mutants will be checked by flow cytometry and fluorescence microscopy. In addition, the lipid translocating properties of the mutant strains will be assessed using fluorescent lipid probes. These studies should contribute to an understanding of how the parasites control the lipid distribution across their membranes. The another aim is to identify the phospholipid presented in the external plasma membrane layer that lead the macrophage to perform the parasite phagocytosis without triggering an inflammatory response. As a strategy, we performed a competition between liposomes constructed with a single phospholipid class, at concentrations of 0.2 µM, 20 µM or 2 mM, and promastigotes of L. (L.) amazonensis in a macrophage (MOI 5:1) infection assay. (AU)

Academic Publications

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

JORGE, Carolina de Lima. Identifications of phospholipid translocators in Leishmania. 2017. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Medicina Tropical de São Paulo (IMT) São Paulo.