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Science 26 August 2005:
Vol. 309. no. 5739, pp. 1384 - 1387
DOI: 10.1126/science.1115257
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Reports

Molecular Mechanism for Switching of P. falciparum Invasion Pathways into Human Erythrocytes

Janine Stubbs,1,2 Ken M. Simpson,1 Tony Triglia,1 David Plouffe,4 Christopher J. Tonkin,1 Manoj T. Duraisingh,1 Alexander G. Maier,1 Elizabeth A. Winzeler,3,4 Alan F. Cowman1*

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.

1 The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia.
2 Cooperative Research Centre for Vaccine Technology and Department of Medical Biology, The University of Melbourne, Victoria 3010, Australia.
3 The Scripps Institute, La Jolla, CA 92037, USA.
4 The Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA.

* To whom correspondence should be addressed. E-mail: cowman{at}wehi.edu.au

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