Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/88610
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Type: Journal article
Title: Reticulocyte and erythrocyte binding-like proteins function cooperatively in invasion of human erythrocytes by malaria parasites
Author: Lopaticki, S.
Maier, A.
Thompson, J.
Wilson, D.
Tham, W.
Triglia, T.
Gout, A.
Speed, T.
Beeson, J.
Healer, J.
Cowman, A.
Citation: Infection and Immunity, 2011; 79(3):1107-1117
Publisher: American Society for Microbiology
Issue Date: 2011
ISSN: 0019-9567
1098-5522
Statement of
Responsibility: 
Sash Lopaticki, Alexander G. Maier, Jennifer Thompson, Danny W. Wilson, Wai-Hong Tham, Tony Triglia, Alex Gout, Terence P. Speed, James G. Beeson, Julie Healer, and Alan F. Cowman
Abstract: Plasmodium falciparum causes the most severe form of malaria in humans and invades erythrocytes using multiple ligand-receptor interactions. Two important protein families involved in erythrocyte binding are the erythrocyte binding-like (EBL) and the reticulocyte binding-like (RBL or P. falciparum Rh [PfRh]) proteins. We constructed P. falciparum lines lacking expression of EBL proteins by creating single and double knockouts of the corresponding genes for eba-175, eba-181, and eba-140 and show that the EBL and PfRh proteins function cooperatively, consistent with them playing a similar role in merozoite invasion. We provide evidence that PfRh and EBL proteins functionally interact, as loss of function of EBA-181 ablates the ability of PfRh2a/b protein antibodies to inhibit merozoite invasion. Additionally, loss of function of some ebl genes results in selection for increased transcription of the PfRh family. This provides a rational basis for considering PfRh and EBL proteins for use as a combination vaccine against P. falciparum. We immunized rabbits with combinations of PfRh and EBL proteins to test the ability of antibodies to block merozoite invasion in growth inhibition assays. A combination of EBA-175, PfRh2a/b, and PfRh4 recombinant proteins induced antibodies that potently blocked merozoite invasion. This validates the use of a combination of these ligands as a potential vaccine that would have broad activity against P. falciparum.
Keywords: Erythrocytes; Reticulocytes; Animals; Rabbits; Humans; Plasmodium falciparum; Malaria; Protozoan Proteins; Malaria Vaccines; Antibodies, Protozoan; Immunoblotting; Enzyme-Linked Immunosorbent Assay; Coculture Techniques; Transfection; Reverse Transcriptase Polymerase Chain Reaction; Gene Knockout Techniques
Rights: Copyright © 2011, American Society for Microbiology. All Rights Reserved.
RMID: 0020138040
DOI: 10.1128/IAI.01021-10
Appears in Collections:Microbiology and Immunology publications

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