Evidence for a switching mechanism in the invasion of erythrocytes by Plasmodium falciparum.
The human malaria parasite Plasmodium falciparum demonstrates variability in its dependence upon erythrocyte sialic acid residues for invasion. Some lines of P. falciparum invade neuraminidase-treated or glycophorin-deficient red blood cells poorly, or not at all, while other lines invade such cells at substantial rates. To explore the molecular basis of non-sialic acid dependent invasion, we selected parasite lines from a clone (Dd2) that initially exhibited low invasion of neuraminidase-treated erythrocytes. After maintaining Dd2 for several cycles in neuraminidase-treated erythrocytes, parasite lines were recovered that invaded both untreated and neuraminidase-treated erythrocytes at equivalently high rates (Dd2/NM). The change in phenotype was maintained after removal of selection pressure. Four subclones of Dd2 were isolated and each readily converted from sialic acid dependence to non-sialic acid dependence during continuous propagation in neuraminidase-treated erythrocytes. The neuraminidase-selected lines and the Dd2 clone demonstrated identical restriction fragment length polymorphism markers indicating that the Dd2 clone was not contaminated during the selection process. Parasite proteins that bound to neuraminidase-treated and untreated erythrocytes were indistinguishable among the parent Dd2 clone and the neuraminidase-selected lines. The ability of the Dd2 parasite to change its invasion requirements for erythrocyte sialic acid suggests a switch mechanism permitting invasion by alternative pathways.
Laboratory of Parasitic Diseases, National Institutes of Health, Bethesda, Maryland 20892.
S A
SA
Dolan
L H
LH
Miller
T E
TE
Wellems
D000818:Animals; D015139:Blotting, Southern; D004247:DNA / Q000235:genetics; D004912:Erythrocytes / Q000469:parasitology*; D006801:Humans; D066298:In Vitro Techniques; D009439:Neuraminidase / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000145:classification / Q000235:genetics / Q000472:pathogenicity*; D012091:Repetitive Sequences, Nucleic Acid; D012794:Sialic Acids / Q000097:blood
D012794:Sialic Acids; D004247:DNA; D009439:Neuraminidase