Plasmodium falciparum GFP-E-NTPDase expression at the intraerythrocytic stages and its inhibition blocks the development of the human malaria parasite

Author(s)

Borges-Pereira, Lucas ; Meissner, Kamila Anna ; Wrenger, Carsten ; Garcia, Celia R. S.

• Document type: Journal article
• Source: PURINERGIC SIGNALLING; v. 13, n. 3, p. 267-277, SEP 2017.
• Web of Science Citations: 2

Abstract

Plasmodium falciparum is the causative agent of the most dangerous form of malaria in humans. It has been reported that the P. falciparum genome encodes for a single ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase), an enzyme that hydrolyzes extracellular tri- and di-phosphate nucleotides. The E-NTPDases are known for participating in invasion and as a virulence factor in many pathogenic protozoa. Despite its presence in the parasite genome, currently, no information exists about the activity of this predicted protein. Here, we show for the first time that P. falciparum E-NTPDase is relevant for parasite lifecycle as inhibition of this enzyme impairs the development of P. falciparum within red blood cells (RBCs). ATPase activity could be detected in rings, trophozoites, and schizonts, as well as qRT-PCR, confirming that E-NTPDase is expressed throughout the intraerythrocytic cycle. In addition, transfection of a construct which expresses approximately the first 500 bp of an E-NTPDase-GFP chimera shows that E-NTPDase co-localizes with the endoplasmic reticulum (ER) in the early stages and with the digestive vacuole (DV) in the late stages of P. falciparum intraerythrocytic cycle. (AU)

• FAPESP's process: 12/12807-3 - Analysis of the redox status and its effect on the proliferation of Plasmodium falciparum in genetically different erythrocytes
• Grantee: Kamila Anna Meissner
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 10/51593-3 - Heterologous expression and biochemical characterization of apyrase from the parasite Plasmodium falciparum
• Grantee: Lucas Borges Pereira
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 15/26722-8 - Drug discovery against human infectious diseases
• Grantee: Carsten Wrenger
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/10288-1 - Analysis of the organelle biogenesis in Plasmodium falciparum by live cell imaging
• Grantee: Carsten Wrenger
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/51295-5 - Functional genomics in Plasmodium
• Grantee: Célia Regina da Silva Garcia
• Support Opportunities: Research Projects - Thematic Grants