Molecular mechanism for switching of P. falciparum invasion pathways into human erythrocytes.
The malaria parasite, Plasmodium falciparum, exploits multiple ligand-receptor interactions, called invasion pathways, to invade the host erythrocyte. Strains of P. falciparum vary in their dependency on sialated red cell receptors for invasion. We show that switching from sialic acid-dependent to -independent invasion is reversible and depends on parasite ligand use. Expression of P. falciparum reticulocyte-binding like homolog 4 (PfRh4) correlates with sialic acid-independent invasion, and PfRh4 is essential for switching invasion pathways. Differential activation of PfRh4 represents a previously unknown mechanism to switch invasion pathways and provides P. falciparum with exquisite adaptability in the face of erythrocyte receptor polymorphisms and host immune responses.
Stubbs
Janine
J
Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia.
Simpson
Ken M
KM
Triglia
Tony
T
Plouffe
David
D
Tonkin
Christopher J
CJ
Duraisingh
Manoj T
MT
Maier
Alexander G
AG
Winzeler
Elizabeth A
EA
Cowman
Alan F
AF
D000818:Animals; D030801:Animals, Genetically Modified; D004912:Erythrocytes / Q000469:parasitology*; D020869:Gene Expression Profiling; D020868:Gene Silencing; D017125:Genes, Protozoan; D006801:Humans; D008024:Ligands; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D009439:Neuraminidase / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D010963:Plasmodium falciparum / Q000235:genetics / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D016133:Polymerase Chain Reaction; D015800:Protozoan Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism; D014158:Transcription, Genetic
D008024:Ligands; D008565:Membrane Proteins; D015800:Protozoan Proteins; C464927:RH4 protein, Plasmodium falciparum; D011993:Recombinant Fusion Proteins; D012794:Sialic Acids; D009439:Neuraminidase