Identification and characterization of an oxidoreductase in Leishmania amazonensis

• Grant number: 17/23696-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): February 01, 2018
• Effective date (End): May 31, 2021
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Lucile Maria Floeter-Winter
• Grantee: Leonardo Cortazzo da Silva
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Leishmania is a protozoan parasite that causes leishmaniases, a disease that presents clinical manifestations ranging from cutaneous lesions to visceral damage, depending on the parasite species and the host's immunological conditions. Leishmania is auxotrophic for L-arginine and presents the machinery for its uptake and metabolism. The amino acid is the common substrate for the enzymes arginase, involved in the polyamines production, and nitric oxide synthase (NOS), involved in nitric oxide (NO) production. Arginase activity is essential for Leishmania amazonensis (La-WT) survival, as well as NO production for promastigote metacyclogenesis and amastigote differentiation. Also, the knockout of arginase in L. amazonensis (La-arg-) altered the production of NO in promastigotes and amastigotes forms. This project is based on the hypothesis that L. amazonensis modifies the expression of the gene encoding an oxidoreductase protein which has a L. mexicana homolog, LmxM19.1450, oxidoreductase-like protein - GI 401419669 -, location 2973-4725, KEGG 1.14.13.39, that possibly is the NOS-like enzyme responsible for NO production during promastigote growth and amastigote differentiation. In order to corroborate this hypothesis, experiments will be carried out to identify the oxidoreductase LmxM19.1450 homologue in L. amazonensis, followed by evaluation of the expression of it transcript in La-WT and La-arg- models in both promastigotes and amastigotes forms. The construction of L. amazonensisoverexpressing this oxidoreductase may demonstrate its function in L-argininedeprivation conditions. (AU)