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Revealing the Sequence and Resulting Cellular Morphology of Receptor-Ligand Interactions during Plasmodium falciparum Invasion of Erythrocytes

During blood stage Plasmodium falciparum infection, merozoites invade uninfected erythrocytes via a complex, multistep process involving a series of distinct receptor-ligand binding events. Understanding each element in this process increases the potential to block the parasite’s life cycle via drug...

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Autores principales: Weiss, Greta E., Gilson, Paul R., Taechalertpaisarn, Tana, Tham, Wai-Hong, de Jong, Nienke W. M., Harvey, Katherine L., Fowkes, Freya J. I., Barlow, Paul N., Rayner, Julian C., Wright, Gavin J., Cowman, Alan F., Crabb, Brendan S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4344246/
https://www.ncbi.nlm.nih.gov/pubmed/25723550
http://dx.doi.org/10.1371/journal.ppat.1004670
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author Weiss, Greta E.
Gilson, Paul R.
Taechalertpaisarn, Tana
Tham, Wai-Hong
de Jong, Nienke W. M.
Harvey, Katherine L.
Fowkes, Freya J. I.
Barlow, Paul N.
Rayner, Julian C.
Wright, Gavin J.
Cowman, Alan F.
Crabb, Brendan S.
author_facet Weiss, Greta E.
Gilson, Paul R.
Taechalertpaisarn, Tana
Tham, Wai-Hong
de Jong, Nienke W. M.
Harvey, Katherine L.
Fowkes, Freya J. I.
Barlow, Paul N.
Rayner, Julian C.
Wright, Gavin J.
Cowman, Alan F.
Crabb, Brendan S.
author_sort Weiss, Greta E.
collection PubMed
description During blood stage Plasmodium falciparum infection, merozoites invade uninfected erythrocytes via a complex, multistep process involving a series of distinct receptor-ligand binding events. Understanding each element in this process increases the potential to block the parasite’s life cycle via drugs or vaccines. To investigate specific receptor-ligand interactions, they were systematically blocked using a combination of genetic deletion, enzymatic receptor cleavage and inhibition of binding via antibodies, peptides and small molecules, and the resulting temporal changes in invasion and morphological effects on erythrocytes were filmed using live cell imaging. Analysis of the videos have shown receptor-ligand interactions occur in the following sequence with the following cellular morphologies; 1) an early heparin-blockable interaction which weakly deforms the erythrocyte, 2) EBA and PfRh ligands which strongly deform the erythrocyte, a process dependant on the merozoite’s actin-myosin motor, 3) a PfRh5-basigin binding step which results in a pore or opening between parasite and host through which it appears small molecules and possibly invasion components can flow and 4) an AMA1–RON2 interaction that mediates tight junction formation, which acts as an anchor point for internalization. In addition to enhancing general knowledge of apicomplexan biology, this work provides a rational basis to combine sequentially acting merozoite vaccine candidates in a single multi-receptor-blocking vaccine.
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spelling pubmed-43442462015-03-04 Revealing the Sequence and Resulting Cellular Morphology of Receptor-Ligand Interactions during Plasmodium falciparum Invasion of Erythrocytes Weiss, Greta E. Gilson, Paul R. Taechalertpaisarn, Tana Tham, Wai-Hong de Jong, Nienke W. M. Harvey, Katherine L. Fowkes, Freya J. I. Barlow, Paul N. Rayner, Julian C. Wright, Gavin J. Cowman, Alan F. Crabb, Brendan S. PLoS Pathog Research Article During blood stage Plasmodium falciparum infection, merozoites invade uninfected erythrocytes via a complex, multistep process involving a series of distinct receptor-ligand binding events. Understanding each element in this process increases the potential to block the parasite’s life cycle via drugs or vaccines. To investigate specific receptor-ligand interactions, they were systematically blocked using a combination of genetic deletion, enzymatic receptor cleavage and inhibition of binding via antibodies, peptides and small molecules, and the resulting temporal changes in invasion and morphological effects on erythrocytes were filmed using live cell imaging. Analysis of the videos have shown receptor-ligand interactions occur in the following sequence with the following cellular morphologies; 1) an early heparin-blockable interaction which weakly deforms the erythrocyte, 2) EBA and PfRh ligands which strongly deform the erythrocyte, a process dependant on the merozoite’s actin-myosin motor, 3) a PfRh5-basigin binding step which results in a pore or opening between parasite and host through which it appears small molecules and possibly invasion components can flow and 4) an AMA1–RON2 interaction that mediates tight junction formation, which acts as an anchor point for internalization. In addition to enhancing general knowledge of apicomplexan biology, this work provides a rational basis to combine sequentially acting merozoite vaccine candidates in a single multi-receptor-blocking vaccine. Public Library of Science 2015-02-27 /pmc/articles/PMC4344246/ /pubmed/25723550 http://dx.doi.org/10.1371/journal.ppat.1004670 Text en © 2015 Weiss et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Weiss, Greta E.
Gilson, Paul R.
Taechalertpaisarn, Tana
Tham, Wai-Hong
de Jong, Nienke W. M.
Harvey, Katherine L.
Fowkes, Freya J. I.
Barlow, Paul N.
Rayner, Julian C.
Wright, Gavin J.
Cowman, Alan F.
Crabb, Brendan S.
Revealing the Sequence and Resulting Cellular Morphology of Receptor-Ligand Interactions during Plasmodium falciparum Invasion of Erythrocytes
title Revealing the Sequence and Resulting Cellular Morphology of Receptor-Ligand Interactions during Plasmodium falciparum Invasion of Erythrocytes
title_full Revealing the Sequence and Resulting Cellular Morphology of Receptor-Ligand Interactions during Plasmodium falciparum Invasion of Erythrocytes
title_fullStr Revealing the Sequence and Resulting Cellular Morphology of Receptor-Ligand Interactions during Plasmodium falciparum Invasion of Erythrocytes
title_full_unstemmed Revealing the Sequence and Resulting Cellular Morphology of Receptor-Ligand Interactions during Plasmodium falciparum Invasion of Erythrocytes
title_short Revealing the Sequence and Resulting Cellular Morphology of Receptor-Ligand Interactions during Plasmodium falciparum Invasion of Erythrocytes
title_sort revealing the sequence and resulting cellular morphology of receptor-ligand interactions during plasmodium falciparum invasion of erythrocytes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4344246/
https://www.ncbi.nlm.nih.gov/pubmed/25723550
http://dx.doi.org/10.1371/journal.ppat.1004670
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