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

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: PURINERGIC SIGNALLING; v. 13, n. 3, p. 267-277, SEP 2017.
• Citações Web of Science: 2

Resumo

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)

• Processo FAPESP: 12/12807-3 - Análise do estado redox e seu efeito sobre a proliferação de Plasmodium falciparum em eritrócitos geneticamente diferentes
• Beneficiário: Kamila Anna Meissner
• Linha de fomento: Bolsas no Brasil - Doutorado
• Processo FAPESP: 11/51295-5 - Genômica funcional em Plasmodium
• Beneficiário: Célia Regina da Silva Garcia
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 15/26722-8 - Drug discovery contra doenças infecciosas humanos
• Beneficiário: Carsten Wrenger
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 13/10288-1 - Análise da biogênese de organelas em Plasmodium falciparum por visualização celular em tempo real
• Beneficiário: Carsten Wrenger
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/51593-3 - Expressão heteróloga e caracterização bioquímica de aspirase do parasita Plasmodium falciparum
• Beneficiário: Lucas Borges Pereira
• Linha de fomento: Bolsas no Brasil - Doutorado Direto