DeaceLeish: investigating the role of lysine deacetylases in the regulation of mechanisms involved in the stage differentiation of Leishmania mexicana

• Grant number: 21/13477-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2022
• Status: Discontinued
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Nilmar Silvio Moretti
• Grantee: Suellen Rodrigues Maran
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated scholarship(s): 23/07783-2 - Modifying to adapt: the impact of lysine deacetylases in Leishmania parasite stage differentiation, BE.EP.DR

Abstract

Leishmania is the etiologic agent of Leishmaniasis, a serious infectious disease, that can manifest itself in three main forms: cutaneous, mucocutaneous and visceral. During its life cycle, the parasite faces different environments and to adapt to these conditions changes the gene expression, translation and metabolism. Protein acetylation is regulated by two family of enzymes, lysine acetyltransferases (KATs), which adds acetyl groups in the lysine residue, and lysine deacetylases (KDACs), which removes these groups. KDACs are divided into two classes: NAD+-dependent (sirtuins) and zinc- dependent (DACs). Proteomic analysis from our group revealed differential protein acetylation among the three main Leishmania mexicana stages (procyclic, metacyclic and amastigote), suggesting a central role of this modification during parasite differentiation. In order to better understanding the function of protein acetylations in this process, we decided to characterize the DACs (DAC1, 3, 4 and 5) of L. mexicana. The preliminary data from our group and presented here, demonstrate that the DACs are involved in key cellular process for L. mexicana stages differentiation. Thus, the main purpose of this project is to investigate the cellular mecanisms that could be regulated by DACs during the process of parasite differentiation. (AU)