Analysis of the organelle biogenesis in Plasmodium falciparum by live cell imaging

• Grant number: 13/10288-1
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2014
• End date: April 30, 2016
• Field of knowledge: Biological Sciences - Parasitology
• Principal Investigator: Carsten Wrenger
• Grantee: Carsten Wrenger
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The malaria parasite Plasmodium falciparum possesses organelles such as mitochondrion and the chloroplast-like compartment named apicoplast which is absent in the human host. Interference with metabolic pathways present in the latter one have been proven be lethal for the parasite. During schizogony P. falciparum need to distribute this organelle to the newly generated merozites which requires the presence of specific proteins. We already identified an enzyme, MinD, belonging to the Min protein of plants. The protein is predicted to be trafficked to the apicoplast and to act as a phosphatase. The aim of the proposed application is to biochemically characterise the recombinant plasmodial enzyme and identify its role in organelle distribution by employing transgenic parasites over-expressing Strep-tagged MinD enzymes. Further mutagenic modifications of PfMinD over-expressing cells will be used to visualise morphological changes of the apicoplast of GFP expressing parasites. The discovery of proteins involved in organelle distribution is very likely to identify novel drug targets, which will be restricted to the parasite. (AU)

Scientific publications

(14)

(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)

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)

KRONENBERGER, THALES; LUNEV, SERGEY; WRENGER, CARSTEN; GROVES, MATTHEW R.. Purification, crystallization and preliminary X-ray diffraction analysis of pyridoxal kinase from Plasmodium falciparum (PfPdxK). ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS, v. 70, n. 11, p. 1550-1555, NOV 2014. (09/54325-2, 11/13706-3, 13/10288-1)

DREBES, JULIA; KUENZ, MADELEINE; PEREIRA, CLAUDIO A.; BETZEL, CHRISTIAN; WRENGER, CARSTEN. MRSA Infections: From Classical Treatment to Suicide Drugs. Current Medicinal Chemistry, v. 21, n. 15, p. 1809-1819, MAY 2014. (13/10288-1, 09/54325-2)

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)

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)

LUNEV, SERGEY; BOSCH, SORAYA S.; BATISTA, FERNANDO DE ASSIS; WRENGER, CARSTEN; GROVES, MATTHEW R.. Crystal structure of truncated aspartate transcarbamoylase from Plasmodium falciparum. ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS, v. 72, n. 7, p. 523-533, JUL 2016. (13/10288-1, 13/17577-9)

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)

DREBES, JULIA; KUENZ, MADELEINE; WINDSHUEGEL, BJOERN; KIKHNEY, ALEXEY G.; MUELLER, INGRID B.; EBERLE, RAPHAEL J.; OBERTHUER, DOMINIK; CANG, HUAIXING; SVERGUN, DMITRI I.; PERBANDT, MARKUS; et al. Structure of ThiM from Vitamin B1 biosynthetic pathway of Staphylococcus aureus - Insights into a novel pro-drug approach addressing MRSA infections. SCIENTIFIC REPORTS, v. 6, MAR 10 2016. (13/10288-1)

KRONENBERGER, THALES; ASSE, JR., LEONARDO RANDER; WRENGER, CARSTEN; GOULART TROSSINI, GUSTAVO HENRIQUE; HONORIO, KATHIA MARIA; MALTAROLLO, VINICIUS GONCALVES. Studies of Staphylococcus aureus FabI inhibitors: fragment-based approach based on holographic structure-activity relationship analyses. Future Medicinal Chemistry, v. 9, n. 2, p. 135-151, JAN 2017. (14/03644-9, 13/10288-1)

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)

KRONENBERGER, THALES; LUNEV, SERGEY; WRENGER, CARSTEN; GROVES, MATTHEW R.. Purification, crystallization and preliminary X-ray diffraction analysis of pyridoxal kinase from Plasmodium falciparum (PfPdxK). ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS, v. 70, p. 6-pg., 2014-11-01. (13/10288-1, 09/54325-2, 11/13706-3)

LUNEV, SERGEY; BOSCH, SORAYA S.; BATISTA, FERNANDO DE ASSIS; WRENGER, CARSTEN; GROVES, MATTHEW R.. Crystal structure of truncated aspartate transcarbamoylase from Plasmodium falciparum. ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS, v. 72, p. 11-pg., 2016-07-01. (13/10288-1, 13/17577-9)