Publication Date:
2011-11-15
Description:
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 are required in all parasite strains, indicating that the parasite is able to access multiple redundant invasion pathways. 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. 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245779/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245779/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crosnier, Cecile -- 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 -- 077108/Wellcome Trust/United Kingdom -- 089084/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 2T32 AI007535-12/AI/NIAID NIH HHS/ -- G19/9/Medical Research Council/United Kingdom -- R01 AI057919/AI/NIAID NIH HHS/ -- R01 AI057919-05/AI/NIAID NIH HHS/ -- R01AI057919/AI/NIAID NIH HHS/ -- R36 CK000119-01/CK/NCEZID CDC HHS/ -- England -- Nature. 2011 Nov 9;480(7378):534-7. doi: 10.1038/nature10606.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22080952" target="_blank"〉PubMed〈/a〉
Keywords:
Antigens, CD147/chemistry/genetics/*metabolism
;
Erythrocytes/metabolism/*parasitology
;
Gene Knockdown Techniques
;
*Host-Parasite Interactions
;
Humans
;
Models, Molecular
;
Plasmodium falciparum/*physiology
;
Protein Structure, Tertiary
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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