title: Cooperativity between Plasmodium falciparum adhesive proteins for invasion into erythrocytes.
abstract: Plasmodium falciparum is the most virulent of the Plasmodium species infective to humans. Different P. falciparum strains vary in their dependence on erythrocyte receptors for invasion and their ability to switch in their utilization of different receptor repertoires. Members of the reticulocyte-binding protein-like (RBL) family of invasion ligands are postulated to play a central role in defining ligand-receptor interactions, known as invasion pathways. Here we report the targeted gene disruption of PfRh2b and PfRh2a in W2mef, a parasite strain that is heavily dependent on sialic-acid receptors for invasion, and show that the PfRh2b ligand is functional in this parasite background. Like the parental line, parasites lacking either PfRh2a or PfR2b can switch to a sialic acid-independent invasion pathway. However, both of the switched lines exhibit a reduced efficiency for invasion into sialic acid-depleted cells, suggesting a role for both PfRh2b and PfRh2a in invasion via sialic acid-independent receptors. We also find a strong selective pressure for the reconstitution of PfRh2b expression at the expense of PfRh2a. Our results reveal the importance of genetic background in ligand-receptor usage by P. falciparum parasites, and suggest that the co-ordinate expression of PfRh2a, PfRh2b together mediate efficient sialic acid-independent erythrocyte invasion.
authors.affiliation: Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: DeSimone
authors.forename: Cameron V
authors.initials: CV
authors.lastname: Jennings
authors.forename: Amy K
authors.initials: AK
authors.lastname: Bei
authors.forename: Christy
authors.initials: C
authors.lastname: Comeaux
authors.forename: Bradley I
authors.initials: BI
authors.lastname: Coleman
authors.forename: Philippe
authors.initials: P
authors.lastname: Refour
authors.forename: Tony
authors.initials: T
authors.lastname: Triglia
authors.forename: Janine
authors.initials: J
authors.lastname: Stubbs
authors.forename: Alan F
authors.initials: AF
authors.lastname: Cowman
authors.forename: Manoj T
authors.initials: MT
authors.lastname: Duraisingh
mesh_terms: D004912:Erythrocytes / Q000469:parasitology*; D018390:Gene Targeting; D006801:Humans; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000235:genetics / Q000472:pathogenicity*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; C551090:Rh2a protein, Plasmodium falciparum; C545352:Rh2b protein, Plasmodium falciparum; C092488:sialic acid receptor; D019158:N-Acetylneuraminic Acid