These authors contributed equally.
Cooperativity between Plasmodium falciparum adhesive proteins for invasion into erythrocytes
Article first published online: 30 MAR 2009
© 2009 The Authors. Journal compilation © 2009 Blackwell Publishing Ltd
Volume 72, Issue 3, pages 578–589, May 2009
How to Cite
DeSimone, T. M., Jennings, C. V., Bei, A. K., Comeaux, C., Coleman, B. I., Refour, P., Triglia, T., Stubbs, J., Cowman, A. F. and Duraisingh, M. T. (2009), Cooperativity between Plasmodium falciparum adhesive proteins for invasion into erythrocytes. Molecular Microbiology, 72: 578–589. doi: 10.1111/j.1365-2958.2009.06667.x
- Issue published online: 21 APR 2009
- Article first published online: 30 MAR 2009
- Accepted 10 March, 2009.
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.