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Study of protein acetylation in Leishmania

Grant number: 18/09948-0
Support type:Regular Research Grants
Duration: November 01, 2018 - April 30, 2021
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Nilmar Silvio Moretti
Grantee:Nilmar Silvio Moretti
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Assoc. researchers:Carolina Borsoi Moraes ; Igor dos Santos Cestari ; Lucio Holanda Gondim de Freitas Junior ; Rafael Lemos Miguez Couñago

Abstract

The study of protein acetylation in different organisms has shown that this post-translational modification is present in proteins involved in several cellular processes. Recently, we characterize the acetyloma of the epimastigote form of Trypanosoma cruzi and the procyclic and bloodstream forms of Trypanosoma brucei. We have verified that these forms have a very different protein acetylation profile, with an enrichment of proteins involved in the mechanisms of response to oxidative stress in T. cruzi, and marked differences in the acetylation levels of enzymes of the glycolytic pathway between the two forms of T. brucei. These observations are in agreement with the adaptations of these parasites during their life cycles. In this project, we will investigate the role of acetylation in regulating the differentiation and progression of infection in Leishmania. In addition, we will explore deacetylases as potential therapeutic targets in these parasites. Thus, we intend to: 1) to investigate the importance of protein acetylation during L. infantum differentiation; 2) to characterize the zinc-dependent deacetylases of L. infantum; 3) to explore lysine deacetylase as drug targets in L. infantum. In this way, this project will allow the establishment of a new research group in our Department, and will contribute to a better understanding of key mechanisms in the biology of these parasites of global medical importance. (AU)

Scientific publications (7)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DOS SANTOS, GREGORY PEDROSO; ABUKAWA, FERNANDA MIDORI; SOUZA-MELO, NORMANDA; ALCANTARA, LAURA MARIA; BITTENCOURT-CUNHA, PAULA; MORAES, CAROLINA BORSOI; JHA, BIJAY KUMAR; MCGWIRE, BRADFORD S.; MORETTI, NILMAR SILVIO; SCHENKMAN, SERGIO. Cyclophilin 19 secreted in the host cell cytosol by Trypanosoma cruzi promotes ROS production required for parasite growth. Cellular Microbiology, DEC 2020. Web of Science Citations: 0.
TUNES, LUIZA G.; MORATO, ROBERTA E.; GARCIA, ADRIANA; SCHMITZ, VINICIUS; STEINDEL, MARIO; CORREA-JUNIOR, JOSE D.; DOS SANTOS, HELIO F.; FREZARD, FREDERIC; DE ALMEIDA, V, MAURO; SILVA, HEVELINE; MORETTI, NILMAR S.; DE BARROS, ANDRE L. B.; DO MONTE-NETO, RUBENS L. Preclinical Gold Complexes as Oral Drug Candidates to Treat Leishmaniasis Are Potent Trypanothione Reductase Inhibitors. ACS INFECTIOUS DISEASES, v. 6, n. 5, p. 1121-1139, MAY 8 2020. Web of Science Citations: 0.
LEITE, ARIELY BARBOSA; SEVERO GOMES, ANTONIEL AUGUSTO; DE CASTRO NASCIMENTO SOUSA, ANA CAROLINE; DE MATTOS FONTES, MARCOS ROBERTO; SCHENKMAN, SERGIO; MORETTI, NILMAR SILVIO. Effect of lysine acetylation on the regulation of Trypanosoma brucei glycosomal aldolase activity. Biochemical Journal, v. 477, n. 9, p. 1733-1744, MAY 2020. Web of Science Citations: 0.
MATUTINO BASTOS, TANIRA; BOTELHO PEREIRA SOARES, MILENA; HADDAD FRANCO, CAIO; ALCANTARA, LAURA; ANTONINI, LORENZO; SABATINO, MANUELA; MAUTONE, NICOLA; HOLANDA FREITAS-JUNIOR, LUCIO; MORAES, CAROLINA BORSOI; RAGNO, RINO; ROTILI, DANTE; SCHENKMAN, SERGIO; MAI, ANTONELLO; SILVIO MORETTI, NILMAR. Identification of Inhibitors to Trypanosoma cruzi Sirtuins Based on Compounds Developed to Human Enzymes. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, n. 10 MAY 2020. Web of Science Citations: 0.
ALTAMURA, FERNANDO; RAJESH, RISHI; CATTA-PRETA, CAROLINA M. C.; MORETTI, NILMAR S.; CESTARI, IGOR. The current drug discovery landscape for trypanosomiasis and leishmaniasis: Challenges and strategies to identify drug targets. Drug Development Research, APR 2020. Web of Science Citations: 2.
WASSANO, NATALIA SAYURI; LEITE, ARIELY BARBOSA; REICHERT-LIMA, FRANQUELINE; SCHREIBER, ANGELICA ZANINELLI; MORETTI, NILMAR S.; DAMASIO, ANDRE. Lysine acetylation as drug target in fungi: an underexplored potential in Aspergillus spp.. Brazilian Journal of Microbiology, v. 51, n. 2 MAR 2020. Web of Science Citations: 0.
BASTOS, TANIRA MATUTINO; RUSSO, HELENA MANNOCHIO; MORETTI, NILMAR SILVIO; SCHENKMAN, SERGIO; MARCOURT, LAURENCE; GUPTA, MAHABIR PRASHAD; WOLFENDER, JEAN-LUC; QUEIROZ, EMERSON FERREIRA; PEREIRA SOARES, MILENA BOTELHO. Chemical Constituents of Anacardium occidentale as Inhibitors of Trypanosoma cruzi Sirtuins. Molecules, v. 24, n. 7 APR 3 2019. Web of Science Citations: 1.

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