Analysis of the redox status and its effect on the proliferation of Plasmodium falciparum in genetically different erythrocytes

• Grant number: 12/12807-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2012
• End date: September 30, 2016
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Carsten Wrenger
• Grantee: Kamila Anna Meissner
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 09/54325-2 - Elucidation of vitamin B metabolism in the human malaria parasite Plasmodium falciparum and their validation as a target for chemotherapy, AP.JP

Abstract

Malaria is one of the most dangerous tropical diseases of our time with more than one million deaths per annum. The worst form of malaria, the malaria tropica, is caused by the parasite Plasmodium falciparum. However some genetic mutations of haemoglobin like sickle cell haemoglobin (HbS) or enzymopathies like glucose-6-phosphate dehydrogenase deficiency are leading to a protection against severe falciparum malaria. Despite years of research the precise mechanisms of protection still has to be discovered although there are few hypothesis. Besides the suggestion of a better innate immune response through an increased degree of phagocytosis, a main role could also be the pro-oxidative habitat inside the red blood cells (RBC) which attenuate the parasite proliferation. Oxidative stress plays a major role for example during the sickle cell disease. By investigation of the redox metabolism of P. falciparum while culturing transgenically modified parasites in abnormal erythrocytes, we will validate the protective role of genetically different red blood cells by focussing on the oxidant defence systems in falciparum malaria and analyse the inhibitory profile of the plasmodial glyoxalase I and II in vitro and in vivo. This should lead us to the identification of novel drug approaches for targeting this deadly pathogen. (AU)

Scientific publications

(9)

(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)

MEISSNER, KAMILA A.; LUNEV, SERGEY; WANG, YUAN-ZE; LINZKE, MARLEEN; BATISTA, FERNANDO DE ASSIS; WRENGER, CARSTEN; GROVES, MATTHEW R.. Drug Target Validation Methods in Malaria - Protein Interference Assay (PIA) as a Tool for Highly Specific Drug Target Validation. CURRENT DRUG TARGETS, v. 18, n. 9, p. 1069-1085, 2017. (13/10288-1, 12/12807-3, 14/23330-9)

LUNEV, SERGEY; BUTZLOFF, SABINE; ROMERO, ATILIO R.; LINZKE, MARLEEN; BATISTA, FERNANDO A.; MEISSNER, KAMILA A.; MUELLER, INGRID B.; ADAWY, ALAA; WRENGER, CARSTEN; GROVES, MATTHEW R.. Oligomeric interfaces as a tool in drug discovery: Specific interference with activity of malate dehydrogenase of Plasmodium falciparum in vitro. PLoS One, v. 13, n. 4, APR 25 2018. (12/12807-3, 14/23330-9, 13/10288-1, 16/24790-9, 15/26722-8)

VASCONCELOS, STANLEY N. S.; MEISSNER, KAMILA A.; FERRAZ, WITOR R.; TROSSINI, GUSTAVO H. G.; WRENGER, CARSTEN; STEFANI, HELIO A.. Indole-3-glyoxyl tyrosine: synthesis and antimalarial activity against Plasmodium falciparum. Future Medicinal Chemistry, v. 11, n. 6, p. 525-538, MAR 2019. (13/17960-7, 12/12807-3, 15/26722-8, 12/00424-2, 17/25543-8, 16/24790-9)

BOSCH, SORAYA S.; KRONENBERGER, THALES; MEISSNER, KAMILA A.; ZIMBRES, FLAVIA M.; STEGEHAKE, DIRK; IZUI, NATALIA M.; SCHETTERT, ISOLMAR; LIEBAU, EVA; WRENGER, CARSTEN. Oxidative Stress Control by Apicomplexan Parasites. BIOMED RESEARCH INTERNATIONAL, 2015. (11/19703-6, 12/12807-3, 11/13706-3, 09/54325-2, 10/20647-0, 13/10288-1, 13/17577-9)

KRONENBERGER, THALES; LINDNER, JASMIN; MEISSNER, KAMILA A.; ZIMBRES, FLAVIA M.; CORONADO, MONIKA A.; SAUER, FRANK M.; SCHETTERT, ISOLMAR; WRENGER, CARSTEN. Vitamin B6-Dependent Enzymes in the Human Malaria Parasite Plasmodium falciparum: A Druggable Target?. BIOMED RESEARCH INTERNATIONAL, 2014. (11/19703-6, 12/12807-3, 11/13706-3, 09/54325-2, 10/20647-0, 13/10288-1, 12/12790-3)

SCARPELLI, PEDRO H.; TESSARIN-ALMEIDA, GIULLIANA; VICOSO, KENIA LOPES; LIMA, WANIA REZENDE; BORGES-PEREIRA, LUCAS; MEISSNER, KAMILA ANNA; WRENGER, CARSTEN; RAFAELLO, ANNA; RIZZUTO, ROSARIO; POZZAN, TULLIO; et al. Melatonin activates FIS1, DYN1, and DYN2 Plasmodium falciparum related-genes for mitochondria fission: Mitoemerald-GFP as a tool to visualize mitochondria structure. Journal of Pineal Research, v. 66, n. 2, MAR 2019. (12/12807-3, 11/51295-5, 14/14347-5, 15/26722-8)

KRONENBERGER, THALES; LINDNER, JASMIN; MEISSNER, KAMILA A.; ZIMBRES, FLAVIA M.; CORONADO, MONIKA A.; SAUER, FRANK M.; SCHETTERT, ISOLMAR; WRENGER, CARSTEN. Vitamin B6-Dependent Enzymes in the Human Malaria Parasite Plasmodium falciparum: A Druggable Target?. BIOMED RESEARCH INTERNATIONAL, v. 2014, p. 11-pg., 2014-01-01. (13/10288-1, 10/20647-0, 12/12790-3, 09/54325-2, 11/13706-3, 12/12807-3, 11/19703-6)

BORGES-PEREIRA, LUCAS; MEISSNER, KAMILA ANNA; WRENGER, CARSTEN; GARCIA, CELIA R. S.. Plasmodium falciparum GFP-E-NTPDase expression at the intraerythrocytic stages and its inhibition blocks the development of the human malaria parasite. PURINERGIC SIGNALLING, v. 13, n. 3, p. 267-277, SEP 2017. (12/12807-3, 10/51593-3, 15/26722-8, 13/10288-1, 11/51295-5)

BOSCH, SORAYA S.; KRONENBERGER, THALES; MEISSNER, KAMILA A.; ZIMBRES, FLAVIA M.; STEGEHAKE, DIRK; IZUI, NATALIA M.; SCHETTERT, ISOLMAR; LIEBAU, EVA; WRENGER, CARSTEN. Oxidative Stress Control by Apicomplexan Parasites. BIOMED RESEARCH INTERNATIONAL, v. 2015, p. 10-pg., 2015-01-01. (13/10288-1, 10/20647-0, 09/54325-2, 11/13706-3, 13/17577-9, 12/12807-3, 11/19703-6)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MEISSNER, Kamila Anna. Analysis of the redox status and its effect on the proliferation of Plasmodium falciparum in genetically different erythrocytes.. 2017. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.