Study of protein acetylation in Leishmania

• Grant number: 18/09948-0
• Support Opportunities: Regular Research Grants
• Duration: November 01, 2018 - October 31, 2021
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Nilmar Silvio Moretti
• Grantee: Nilmar Silvio Moretti
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated 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

(15)

(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)

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. (18/09948-0)

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. (17/22669-0, 18/09948-0)

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. (18/09948-0, 15/22031-0)

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, v. 23, n. 4, DEC 2020. (18/09948-0, 17/02416-0, 17/19303-4, 18/07766-2)

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; et al. 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. (18/09948-0, 15/22031-0)

SILVA, RAFAEL DE FREITAS E; BASSI, GABRIELA; CAMARA, NIELS OLSEN SARAIVA; MORETTI, NILMAR SILVIO. Sirtuins: Key pieces in the host response to pathogens' puzzle. Molecular Immunology, v. 160, p. 11-pg., 2023-07-10. (18/09948-0, 20/07870-4, 22/03075-0)

DOS SANTOS MOURA, LEILA; SANTANA NUNES, VINICIUS; GOMES, ANTONIEL A. S.; SOUSA, ANA CAROLINE DE CASTRO NASCIMENTO; FONTES, MARCOS R. M.; SCHENKMAN, SERGIO; MORETTI, NILMAR SILVIO. Mitochondrial Sirtuin TcSir2rp3 Affects TcSODA Activity and Oxidative Stress Response in Trypanosoma cruzi. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 11, NOV 11 2021. (14/03714-7, 20/07870-4, 18/09948-0, 15/22031-0)

MONTE-NETO, RUBENS L.; FERNANDEZ-PRADA, CHRISTOPHER; MORETTI, NILMAR S.. Sex under pressure: stress facilitates Leishmania in vitro hybridization. Trends in Parasitology, v. 38, n. 4, p. 3-pg., 2022-03-09. (18/09948-0)

FERREIRA, TIAGO R.; COUNAGO, RAFAEL M.; MORETTI, NILMAR S.. Raising the Bar(-seq) in Leishmania Genetic Screens. Trends in Parasitology, v. 37, n. 5, p. 3-pg., 2021-04-14. (18/09948-0, 13/50724-5, 14/50897-0)

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, v. 83, n. 2, p. 28-pg., 2020-04-06. (18/09948-0)

TEIXEIRA, SAMUEL COTA; DA SILVA, MARCELO SANTOS; GOMES, ANTONIEL AUGUSTO SEVERO; MORETTI, NILMAR SILVIO; LOPES, DAIANA SILVA; FERRO, ELOISA AMALIA VIEIRA; RODRIGUES, VERIDIANA DE MELO. Panacea within a Pandora's box: the antiparasitic effects of phospholipases A(2) (PLA(2)s) from snake venoms. Trends in Parasitology, v. 38, n. 1, p. 80-94, JAN 2022. (18/09948-0, 19/10753-2, 20/10277-3)

MARAN, SUELLEN RODRIGUES; FLECK, KRISTA; MONTEIRO-TELES, NATALIA MELQUIE; ISEBE, TONY; WALRAD, PEGINE; JEFFERS, VICTORIA; CESTARI, IGOR; VASCONCELOS, ELTON J. R.; MORETTI, NILMAR. Protein acetylation in the critical biological processes in protozoan parasites. Trends in Parasitology, v. 37, n. 9, p. 815-830, SEP 2021. (19/13765-1, 18/09948-0)

SAENZ-GARCIA, JOSE L.; BORGES, BEATRIZ S.; SOUZA-MELO, NORMANDA; MACHADO, LUIZ V.; MIRANDA, JULIANA S.; PACHECO-LUGO, LISANDRO ALFONSO; MORETTI, NILMAR S.; WHELEER, RICHARD; SOARES MEDEIROS, LIA C.; DAROCHA, WANDERSON D.. rypanin Disruption Affects the Motility and Infectivity of the Protozoan Trypanosoma cruz. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 11, JAN 7 2022. (18/09948-0, 20/07870-4)

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. (15/22031-0, 18/09948-0)

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; et al. 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. (18/09948-0)