Affiliation:
1. W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
Abstract
ABSTRACT
Malaria kills more than 1 million people per year worldwide, with severe malaria anemia accounting for the majority of the deaths. Malaria anemia is multifactorial in etiology, including infected erythrocyte destruction and decrease in erythrocyte production, as well as destruction or clearance of noninfected erythrocytes. We identified a panspecies
Plasmodium
hemolysin type III related to bacterial hemolysins. The identification of a hemolysin III homologue in
Plasmodium
suggests a potential role in host erythrocyte lysis. Here, we report the first characterization of
Plasmodium falciparum
hemolysin III, showing that the soluble recombinant
P. falciparum
hemolysin III is a pore-forming protein capable of lysing human erythrocytes in a dose-, time-, and temperature-dependent fashion. The recombinant
P. falciparum
hemolysin III-induced hemolysis was partially inhibited by glibenclamide, a known channel antagonist. Studies with polyethylene glycol molecules of different molecular weights indicated a pore size of approximately 3.2 nm. Heterologous expression of recombinant
P. falciparum
hemolysin III in
Xenopus
oocytes demonstrated early hypotonic lysis similar to that of the pore-forming aquaporin control. Live fluorescence microscopy localized transfected recombinant green fluorescent protein (GFP)-tagged
P. falciparum
hemolysin III to the essential digestive vacuole of the
P. falciparum
parasite. These transfected trophozoites also possessed a swollen digestive vacuole phenotype. Native
Plasmodium
hemolysin III in the digestive vacuole may contribute to lysis of the parasitophorous vacuole membrane derived from the host erythrocyte. After merozoite egress from infected erythrocytes, remnant
P. falciparum
hemolysin III released from digestive vacuoles could potentially contribute to lysis of uninfected erythrocytes to contribute to severe life-threatening anemia.
Publisher
American Society for Microbiology
Subject
Molecular Biology,General Medicine,Microbiology
Cited by
9 articles.
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