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Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum

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Erythrocyte invasion by Plasmodium falciparum is central to the pathogenesis of malaria. Invasion requires a series of extracellular recognition events between erythrocyte receptors and ligands on the merozoite, the invasive form of the parasite. None of the few known receptor–ligand interactions involved1,2,3,4 are required in all parasite strains, indicating that the parasite is able to access multiple redundant invasion pathways5. Here, we show that we have identified a receptor–ligand pair that is essential for erythrocyte invasion in all tested P. falciparum strains. By systematically screening a library of erythrocyte proteins, we have found that the Ok blood group antigen, basigin, is a receptor for PfRh5, a parasite ligand that is essential for blood stage growth6. Erythrocyte invasion was potently inhibited by soluble basigin or by basigin knockdown, and invasion could be completely blocked using low concentrations of anti-basigin antibodies; importantly, these effects were observed across all laboratory-adapted and field strains tested. Furthermore, Oka− erythrocytes, which express a basigin variant that has a weaker binding affinity for PfRh5, had reduced invasion efficiencies. Our discovery of a cross-strain dependency on a single extracellular receptor–ligand pair for erythrocyte invasion by P. falciparum provides a focus for new anti-malarial therapies.

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Figure 1: BSG is an erythrocyte receptor for PfRh5.
Figure 2: Soluble BSG, anti-BSG antibodies and BSG knockdown potently block erythrocyte invasion.
Figure 3: The Ok a− BSG variant has reduced binding affinity for PfRh5 and Ok a− erythrocytes have reduced merozoite invasion frequencies.

Change history

  • 21 December 2011

    The Competing Financial Interests statement appeared incorrectly in the AOP PDF version. This has been corrected.


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We are grateful to the Oka− blood donors. We thank V. Horejsi for monoclonal antibodies and D. Ahr for technical assistance. This work was supported by the Wellcome Trust grant numbers 077108 (G.J.W.) and 089084 (J.C.R.) and National Institutes of Health R01AI057919 (M.T.D.). A.K.B. is supported by a Center for Disease Control grant R36 CK000119-01 and an Epidemiology of Infectious Disease and Biodefense Training Grant 2T32 AI007535-12.

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Authors and Affiliations



C.C. compiled the erythrocyte protein library and identified the PfRh5–BSG interaction. L.Y.B. led the P. falciparum functional validation, with support from M.T. S.J.B. performed the biochemical and biophysical characterization of the interaction. A.K.B. performed the lentiviral knockdown and parasite invasion experiments under the direction of M.T.D. M.U. provided the Oka− blood samples and matching controls. O.N. and S.M. supervised the collection and culturing of field strains. D.P.K. performed genetic analysis on the BSG and PfRh5 loci. G.J.W. and J.C.R. conceived and supervised the project, and wrote the manuscript.

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Correspondence to Julian C. Rayner or Gavin J. Wright.

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Competing interests

C.C., L.Y.B., S.J.B., J.C.R. and G.J.W. are named on a patent application relating to this work.

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Crosnier, C., Bustamante, L., Bartholdson, S. et al. Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum. Nature 480, 534–537 (2011).

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