Erythrocyte-binding antigen 175 mediates invasion in Plasmodium falciparum utilizing sialic acid-dependent and -independent pathways
- Author(s)
- Duraisingh, MT; Maier, AG; Triglia, T; Cowman, AF;
- Details
- Publication Year 2003-04-15,Volume 100,Issue #8,Page 4796-4801
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Publication Type
- Journal Article
- Abstract
- The Plasmodium falciparum erythrocyte-binding antigen 175 (EBA-175) is a ligand for merozoite invasion into human erythrocytes that binds to glycophorin A in a sialic acid-dependent manner. A falciparum, strain W2mef depends on sialic acid for invasion of erythrocytes, whereas 3D7 is sialic acid-independent. We generated parasites that lack expression or express truncated forms of EBA-175 in W2mef and 3D7. Lack of EBA-175 expression in W2mef parasites was associated with a switch to sialic acid-independent invasion. 3D7 parasites lacking expression of EBA-175 showed no alteration in their ability to utilize sialic acid-independent pathways. Strikingly, both W2mef and 3D7 parasites lacking EBA-175 expression invaded chymotrypsin-treated erythrocytes inefficiently compared with the parental lines. This loss of function suggests that the EBA-175/glycophorin A ligand-receptor interaction is the major chymotrypsin-resistant invasion pathway. Parasite lines with truncated EBA-175 had invasion phenotypes equivalent to parasites lacking expression of EBA-175. The EBA-175 ligand is functional in erythrocyte invasion by merozoites that utilize either sialic acid-dependent or independent invasion pathways. This finding suggests a model where a minimal affinity supplied by multiple ligand-receptor interactions is required for successful invasion and has implications for EBA-175 as a malaria vaccine candidate.
- Publisher
- NATL ACAD SCIENCES
- Keywords
- RECEPTOR-BINDING; MALARIA PARASITES; GLYCOPHORIN-B; EBA-175; ANTIBODIES; FAMILY; MEROZOITES; DISRUPTION; DOMAIN; LIGAND
- Publisher's Version
- https://doi.org/10.1073/pnas.0730883100
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2003-04-15 12:00:00