Invasion by P. falciparum merozoites suggests a hierarchy of molecular interactions.
Central to the pathology of malaria disease are the repeated cycles of parasite invasion and destruction of human erythrocytes. In Plasmodium falciparum, the most virulent species causing malaria, erythrocyte invasion involves several specific receptor-ligand interactions that direct the pathway used to invade the host cell, with parasites varying in their dependency on these different pathways. Gene disruption of a key invasion ligand in the 3D7 parasite strain, the P. falciparum reticulocyte binding-like homolog 2b (PfRh2b), resulted in the parasite invading via a novel pathway. Here, we show results that suggest the molecular basis for this novel pathway is not due to a molecular switch but is instead mediated by the redeployment of machinery already present in the parent parasite but masked by the dominant role of PfRh2b. This would suggest that interactions directing invasion are organized hierarchically, where silencing of dominant invasion ligands reveal underlying alternative pathways. This provides wild parasites with the ability to adapt to immune-mediated selection or polymorphism in erythrocyte receptors and has implications for the use of invasion-related molecules in candidate vaccines.
Baum
Jake
J
Division of Infection and Immunity, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Maier
Alexander G
AG
Good
Robert T
RT
Simpson
Ken M
KM
Cowman
Alan F
AF
D000818:Animals; D004912:Erythrocytes / Q000469:parasitology; D017125:Genes, Protozoan; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood / Q000235:genetics* / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity*; D011956:Receptors, Cell Surface / Q000097:blood; D014158:Transcription, Genetic
D011956:Receptors, Cell Surface