Malaria is still a devastating disease with 228 million cases globally and 405,000 lethal outcomes in 2018, mainly in children under five years of age. The threat of emerging malaria strains resistant to currently available drugs has made the search for novel drug targets compelling. The process by which Plasmodium falciparum parasites invade the host cell has been widely studied, but only a few erythrocyte proteins involved in this process have been identified so far. The erythrocyte protein Rac1 is a GTPase that plays an important role in host cell invasion by many intracellular pathogens. Here we show that Rac1 is recruited in proximity to the site of parasite entry during P. falciparum invasion process and that subsequently localizes to the parasitophorous vacuole membrane. We also suggest that this GTPase may be involved in erythrocyte invasion by P. falciparum, by testing the effect of specific Rac1 inhibitory compounds. Finally, we suggest a secondary role of the erythrocyte GTPase also in parasite intracellular development. We here characterize a new erythrocyte protein potentially involved in P. falciparum invasion of the host cell and propose the human GTPase Rac1 as a novel and promising antimalarial drug target.

Characterization of the erythrocyte GTPase Rac1 in relation to Plasmodium falciparum invasion / S. Paone, S. D'Alessandro, S. Parapini, F. Celani, V. Tirelli, M. Pourshaban, A. Olivieri. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 10:1(2020), pp. 22054.1-22054.12. [10.1038/s41598-020-79052-0]

Characterization of the erythrocyte GTPase Rac1 in relation to Plasmodium falciparum invasion

D'Alessandro S.;Parapini S.;
2020

Abstract

Malaria is still a devastating disease with 228 million cases globally and 405,000 lethal outcomes in 2018, mainly in children under five years of age. The threat of emerging malaria strains resistant to currently available drugs has made the search for novel drug targets compelling. The process by which Plasmodium falciparum parasites invade the host cell has been widely studied, but only a few erythrocyte proteins involved in this process have been identified so far. The erythrocyte protein Rac1 is a GTPase that plays an important role in host cell invasion by many intracellular pathogens. Here we show that Rac1 is recruited in proximity to the site of parasite entry during P. falciparum invasion process and that subsequently localizes to the parasitophorous vacuole membrane. We also suggest that this GTPase may be involved in erythrocyte invasion by P. falciparum, by testing the effect of specific Rac1 inhibitory compounds. Finally, we suggest a secondary role of the erythrocyte GTPase also in parasite intracellular development. We here characterize a new erythrocyte protein potentially involved in P. falciparum invasion of the host cell and propose the human GTPase Rac1 as a novel and promising antimalarial drug target.
Humans; Intracellular Membranes; Plasmodium falciparum; rac1 GTP-Binding Protein; Erythrocytes; Vacuoles
Settore MED/04 - Patologia Generale
Settore MED/46 - Scienze Tecniche di Medicina di Laboratorio
Settore MED/07 - Microbiologia e Microbiologia Clinica
Settore VET/06 - Parassitologia e Malattie Parassitarie degli Animali
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/902331
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