Characterization of Leishmania infantum - macrophage interaction: Identification of binding proteins in L. infantum through synthetic peptides selected by phage display technique

• Grant number: 23/07154-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2023
• End date: February 28, 2025
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Marcia Aparecida Silva Graminha
• Grantee: Ana Clara Lunardi Yagi
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Leishmaniases are a group of diseases caused by protozoa of the genus Leishmania and endanger 350 million people worldwide. There are few available drugs for the treatment of this parasitic disease that present several drawbacks such as high toxicity and low efficacy, turning urgent the search for new drugs. The transmission occurs by the inoculation of metacyclic promastigotes into the host's skin during the blood meal of sandflies. The promastigotes are then preferentially phagocytosed by macrophages, followed by differentiation to amastigotes. Thus, the Leishmania-host interaction can be explored in order to identify new drug targets for leishmaniasis control. Using Phage Display methodology, we identified a 12 amino acid peptide capable of reducing by ~52% the infection rate of macrophages infected by Leishmania infantum, Leishmania amazonensis or Leishmania mexicana. Additionally, BALB/c mice infected with L. infantum promastigotes at the stationary phase previously incubated with the peptide reduced by 80% the parasite load in the liver. The obtained data suggest that this peptide might be interacting with ligands present on the parasite surface, interfering with the parasite-host cell infection process. Thus, the main goal of this proposal is to identify by far-western blot and pulldown assays, followed by mass spectrometry analysis, a putative L. infantum ligand whose host cell interaction is disrupetd by the peptide contributing to the understanding of the internalization process of the Leishmania parasite and for the discovery of new therapeutic targets for the control of leishmaniasis.