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Sequential roles for red blood cell binding proteins enable phased commitment to invasion for malaria parasites

Hart, Melissa N.; Mohring, Franziska; DonVito, Sophia M.; Thomas, James A.; Muller-Sienerth, Nicole; Wright, Gavin J.; Knuepfer, Ellen; Saibil, Helen R.; Moon, Robert W.


Melissa N. Hart

Franziska Mohring

Sophia M. DonVito

James A. Thomas

Nicole Muller-Sienerth

Gavin J. Wright

Ellen Knuepfer

Helen R. Saibil

Robert W. Moon


Invasion of red blood cells (RBCs) by Plasmodium merozoites is critical to their continued survival within the host. Two major protein families, the Duffy binding-like proteins (DBPs/EBAs) and the reticulocyte binding like proteins (RBLs/RHs) have been studied extensively in P. falciparum and are hypothesized to have overlapping, but critical roles just prior to host cell entry. The zoonotic malaria parasite, P. knowlesi, has larger invasive merozoites and contains a smaller, less redundant, DBP and RBL repertoire than P. falciparum.OneDBP (DBPα) and one RBL, normocyte binding protein Xa (NBPXa) are essential for invasion of human RBCs. Taking advantage of the unique biological features of P. knowlesi and iterative CRISPR-Cas9 genome editing, we determine the precise order of key invasion milestones and demonstrate distinct roles for each family. These distinct roles support a mechanism for phased commitment to invasion and can be targeted synergistically with invasion inhibitory antibodies.


Hart, M. N., Mohring, F., DonVito, S. M., Thomas, J. A., Muller-Sienerth, N., Wright, G. J., …Moon, R. W. (in press). Sequential roles for red blood cell binding proteins enable phased commitment to invasion for malaria parasites. Nature Communications, 14(1), 4619.

Journal Article Type Article
Acceptance Date Jul 20, 2023
Online Publication Date Aug 1, 2023
Deposit Date Sep 5, 2023
Publicly Available Date Sep 6, 2023
Journal Nature Communications
Publisher Nature Research
Peer Reviewed Peer Reviewed
Volume 14
Issue 1
Pages 4619
Keywords Malaria; host pathogen interaction; Red blood cells; Genetics and Molecular Biology; vaccine target; Multidisciplinary


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