Erythrocyte-binding antigen 175 mediates invasion in Plasmodium falciparum utilizing sialic acid-dependent and -independent pathways.
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. P. 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.
Duraisingh
Manoj T
MT
The Walter and Eliza Hall Institute of Medical Research, Melbourne 3050, Australia.
Maier
Alexander G
AG
Triglia
Tony
T
Cowman
Alan F
AF
D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D016054:DNA, Protozoan / Q000235:genetics; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D006021:Glycophorins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D009154:Mutation; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D000953:Antigens, Protozoan; D002352:Carrier Proteins; D016054:DNA, Protozoan; D006021:Glycophorins; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C065668:erythrocyte-binding antigen 175, Plasmodium; D019158:N-Acetylneuraminic Acid