Involvement of Plasmodium proteases in the pathophysiology of malaria

• Grant number: 15/11861-2
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2016
• End date: July 31, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Enzymology
• Principal Investigator: Adriana Karaoglanovic Carmona
• Grantee: Adriana Karaoglanovic Carmona
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Marcos Leoni Gazarini Dutra

Abstract

The purpose of this project is to use the experience of our group, gained in over 20 years of work with proteolytic enzymes, to characterize proteases of Plasmodium and theirs involvement in the pathophysiology of malaria. Analysis of the P. falciparum genome has allowed the identification of approximately 90 proteases that are involved in numerous processes, including degradation of hemoglobin, erythrocyte invasion and egress. However, the role of these enzymes in the degradation of other plasmatic proteins of the host is underexplored and may be an important element in the understanding of the parasite-host interaction.Studies carried out by our group showed that Plasmodium peptidases are able to hydrolyze the host kininogen and plasminogen. Continuing the work, in this project we will investigate in more detail the processing and internalization of these plasmatic proteins by P. falciparum. We will also investigate the influence of the kinins generated by P. falciparum and P. chabaudi in the pathophysiology of the host in vitro assays using cultured mammalian cells and in vivo in murine infection model. Furthermore, we will also examine the involvement of P. falciparum calmodulin in calcium homeostasis and in modulation of the proteolytic activity of the parasite through the signaling pathways. (AU)

Scientific publications

(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)

GOMES SMAUL, MAYRIM MACHADO; BUDU, ALEXANDRE; MONTAGNA, GEORGINA NURI; DA SILVA FERRARA, TAISE FERNANDA; MALUF, SARAH EL CHAMY; BAGNARESI, PIERO; FERREIRA MACHADO, MARCELO MARCONDES; DOS SANTOS, FELLIPE BRONZE; DE AZEVEDO, MAURO FERREIRA; CARMONA, ADRIANA KARAOGLANOVIC; et al. Plasmodium falciparum histidine triad protein and calmodulin modulates calcium homeostasis and intracellular proteolysis. Biochemical and Biophysical Research Communications, v. 503, n. 2, p. 722-728, SEP 5 2018. (12/24278-5, 16/15298-3, 14/07138-0, 16/02412-2, 15/19316-3, 13/12913-0, 15/00689-4, 15/11861-2, 15/07182-2, 11/20941-9)

VENTURA, PRISCILLA D. S.; CARVALHO, CAROLINA P. F.; BARROS, NILANA M. T.; MARTINS-SILVA, LEONARDO; DANTAS, EDILSON O.; MARTINEZ, CAROLINA; MELO, POLLYANA M. S.; PESQUERO, JOAO B.; CARMONA, ADRIANA K.; NAGAOKA, MARCIA R.; et al. Malaria infection promotes a selective expression of kinin receptors in murine liver. Malaria Journal, v. 18, JUN 24 2019. (15/11861-2, 14/22206-2)

FERRARA, TAISE F. S.; SCHNEIDER, VANESSA K.; LIMA, PATRICIA SILVA; BRONZE, FELLIPE S.; MACHADO, MARCELO F. M.; HENRIQUE-SILVA, FLAVIO; SOARES-COSTA, ANDREA; CARMONA, ADRIANA K.. Gene expression studies and molecular characterization of a cathepsin L-like from the Asian citrus psyllid Diaphorina citri, vector of Huanglongbing. International Journal of Biological Macromolecules, v. 158, p. 375-383, SEP 1 2020. (16/02412-2, 15/11861-2)