Role of Proteases During Intra-erythrocytic Developmental Cycle of Human Malaria Parasite Plasmodium falciparum
Malaria remains a major parasitic disease in the tropical and sub-tropical countries mainly due to dramatic increase in parasite lines resistant to commonly used anti-malarials. Characterization of novel metabolic pathways in the parasites and understandi
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Abstract Malaria remains a major parasitic disease in the tropical and sub-tropical countries mainly due to dramatic increase in parasite lines resistant to commonly used anti-malarials. Characterization of novel metabolic pathways in the parasites and understanding their functional role is a prerequisite to design new anti-malarial strategies. Parasite proteases play key role in growth and differentiation of all the developmental stages across the parasite life cycle and present the most promising targets to develop new drugs against malaria. In Plasmodium falciparum genome database a total of 123 proteases are identified; these proteases belong to five different clans: Cysteine, Aspartic, Serine, Metallo-, and Threonine. Some of the most studied parasite proteases are those that are functional in the asexual blood stage cycle. Starting with the processing of key parasite ligand in merozoite, the invasive form of blood stage parasite, degradation of host hemoglobin in food-vacuole, regulation of levels of key metabolic pathways in cytosol and cellular organelles, degradation of misfolded and unused proteins, and rupture of host membrane for egress of daughter merozoites is mediated by these proteases. Here we discuss roles of some of the parasite proteases involved in various steps of the parasite intraerythrocytic cycle. Keywords Malaria • Plasmodium falciparum • Intra-erythrocytic cycle • Merozoite invasion • Merozoite egress • Hemoglobin degradation • Organelle proteases
S. Rathore • S. Jain • M. Asad • G. Datta • P. Malhotra • A. Mohmmed (*) International Centre for Genetic Engineering and Biotechnology, New Delhi 110 067, India e-mail: [email protected] S. Chakraborti and N.S. Dhalla (eds.), Proteases in Health and Disease, Advances in Biochemistry in Health and Disease 7, DOI 10.1007/978-1-4614-9233-7_13, © Springer Science+Business Media New York 2013
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Introduction
The phylum Apicomplexa includes various protozoan pathogens causing major parasite diseases in the developing world; the most important of these diseases is malaria which causes about 1 million deaths globally per year [1]. Malaria is caused by five different species of genus Plasmodium: P. falciparum, P. vivax, P. malariae, P. ovale, and P. knowlesi; among them P. falciparum is responsible for the most deadly form of malaria infections. Plasmodium has a complex life cycle which is completed in three major phases in two host systems. Infection in humans begins with a bite of infected female Anopheles mosquito that injects invasive form of the parasite, sporozoites, which reaches to liver hepatocytes. The sporozoite enter and exits several hepatocytes by ripping through the plasma-membrane before finally infecting one of the host cell. In the infected hepatocytes the parasite resides in a parasitophorous vacuole (PV), undergoes multiple rounds of mitotic nuclear division and organelle division and subsequently large number of merozoites are formed which are released into the blood stream. Merozoites are the bloo
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