Blocking Basigin Binding Prevents Erythrocyte Invasion by Malaria Parasites

The red blood cell protein basigin has been identified as the focus for attachment and invasion of human erythrocytes by the malaria parasite Plasmodium falciparum.

Investigators at the Wellcome Trust Sanger Institute (Cambridge, United Kingdom) used their novel AVEXIS (Avidity-based Extracellular Interaction Screen) screening method to search a library of erythrocyte proteins for those with specific P. falciparum binding capability.

They reported in the November 9, 2011, online edition of the journal Nature that basigin, the Ok blood group antigen, is a receptor for PfRh5, a parasite ligand that is essential for blood stage growth. Basigin (BSG), also known as extracellular matrix metalloproteinase inducer (EMMPRIN) or cluster of differentiation 147 (CD147), is a protein that in humans is encoded by the BSG gene. This protein is a determinant for the Ok blood group system.

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. These effects were observed across all laboratory-adapted and field strains of P. falciparum tested. Furthermore, erythrocytes that expressed a basigin variant with weaker binding affinity for PfRh5 had reduced invasion efficiencies.

This discovery of a cross-strain dependency on a single extracellular receptor–ligand pair for erythrocyte invasion by P. falciparum provides a focus for new antimalarial therapies. “Our findings were unexpected and have completely changed the way in which we view the invasion process,” said senior author Dr. Gavin Wright, head of the cell surface signaling laboratory at the Wellcome Trust Sanger Institute. “Our research seems to have revealed an Achilles' heel in the way the parasite invades our red blood cells. It is rewarding to see how our techniques can be used to answer important biological problems and lay the foundations for new therapies.”

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Wellcome Trust Sanger Institute