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Plasmodium falciparum signal peptide peptidase is a promising drug target against blood stage malaria |
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| Authors: | Xuerong Li Noemi Bahamontes-Rosa Boubacar Traore Athar H. Chishti |
| Affiliation: | a Department of Pharmacology, University of Illinois College of Medicine, 909 South Wolcott Avenue, UIC Cancer Center, MC-704 Room 5100, Chicago, IL 60612, USA b Department of Parasitology, University of Tubingen, Germany c Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali d Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA |
| Abstract: | The resistance of malaria parasites to current anti-malarial drugs is an issue of major concern globally. Recently we identified a Plasmodium falciparum cell membrane aspartyl protease, which binds to erythrocyte band 3, and is involved in merozoite invasion. Here we report the complete primary structure of P. falciparum signal peptide peptidase (PfSPP), and demonstrate that it is essential for parasite invasion and growth in human erythrocytes. Gene silencing suggests that PfSPP may be essential for parasite survival in human erythrocytes. Remarkably, mammalian signal peptide peptidase inhibitors (Z-LL)2-ketone and L-685,458 effectively inhibited malaria parasite invasion as well as growth in human erythrocytes. In contrast, DAPT, an inhibitor of a related γ-secretase/presenilin-1, was ineffective. Thus, SPP inhibitors specific for PfSPP may function as potent anti-malarial drugs against the blood stage malaria. |
| Keywords: | Malaria Plasmodium falciparum Signal peptide peptidase Intramembrane aspartyl protease Erythrocyte Band 3 Presenilins |
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