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The importance of proteases provision essential amino acids sources in Leishmania (Leishmania) infantum promastigotes

Grant number: 16/15738-3
Support type:Scholarships in Brazil - Master
Effective date (Start): August 01, 2017
Effective date (End): July 31, 2019
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Heitor Franco de Andrade Junior
Grantee:Thiago Fidelis Ferrão
Home Institution: Instituto de Medicina Tropical de São Paulo (IMT). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Visceral leishmaniasis (VL) is a disease widely distributed worldwide that infects more than 300,000 people a year, which can lead to death 95% of symptomatic cases without treatment and that is epidemic in Brazil. In vertebrates, it is a parasite of cells of the mononuclear phagocytic system and the medicines used have important side effects. The species responsible for LV in Brazil is Leishmania (Leishmania) infantum, its transmission occurs through sandflies Lutzomyia longipalpis. Dogs are the main reservoirs in urban regions and can transmit parasites to man by blood meal sandfly. In vertebrate hosts, their growth is slow and occurs within acidic parasitoid vacuoles. Your nutrition to depend on essential amino acids obtained from the host cell or degradation proteins presents in parasitoid vacuoles. The major proteases present in the genus leishmania belong to four groups that are classified according to the active radical site, cysteine, aspartic, serine or metal. In this project we demonstrate to study the importance of different groups of proteases, not processing proteins offered to promastigotes as the only source of amino acids in culture, and for that, to use selective inhibitors of cysteine, aspartic, serine and metallo proteases. The source of these amino acids will be used fluorescently labeled proteins and their digestion revealed by the release of the fluorochrome or its accumulation. We expect that those data clarify a dependence of the parasite on its proteases for an acquisition of essential amino acids in its development, providing useful information for production of new drugs for selective inactivation enzymes and causing parasite death (AU)