Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum

• Published in: Nature (London) Vol. 480; no. 7378; pp. 534 - 537
• Main Authors: Crosnier, Cécile, Bustamante, Leyla Y., Bartholdson, S. Josefin, Bei, Amy K., Theron, Michel, Uchikawa, Makoto, Mboup, Souleymane, Ndir, Omar, Kwiatkowski, Dominic P., Duraisingh, Manoj T., Rayner, Julian C., Wright, Gavin J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22-12-2011; Nature Publishing Group
• Subjects: 631/250/255/1715; 631/326/417; 631/45/612/1237; 631/80/84/2336; Basigin - chemistry; Basigin - genetics; Basigin - metabolism; Causes of; Erythrocytes - metabolism; Erythrocytes - parasitology; Gene Knockdown Techniques; Host-Parasite Interactions; Humanities and Social Sciences; Humans; letter; Malaria; Models, Molecular; multidisciplinary; Physiological aspects; Plasmodium falciparum; Plasmodium falciparum - physiology; Protein Structure, Tertiary; Science; Science (multidisciplinary); United Kingdom
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/nature10606

No entry for malaria parasites
The ability to prevent or impair the invasion of erythrocytes by the
Plasmodium falciparum
merozoite, the initial blood stage of malaria infection, has long been an ambition for those working on antimalarial therapeutics. It has proved elusive, but comes a step closer with the identification of a specific interaction between the parasite ligand PfRh5 and the erythrocyte receptor basigin, which is essential for parasite invasion of erythrocytes. Invasion can be inhibited by anti-basigin antibodies in all laboratory-adapted and field strains of
P. falciparum
tested, providing a promising starting point for the development of invasion-blocking drugs and vaccines.
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 involved
1
,
2
,
3
,
4
are required in all parasite strains, indicating that the parasite is able to access multiple redundant invasion pathways
5
. 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 growth
6
. 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, Ok
a−
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.