Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/113501
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Type: Journal article
Title: Cellular dissection of malaria parasite invasion of human erythrocytes using viable Plasmodium knowlesi merozoites
Author: Lyth, O.
Vizcay-Barrena, G.
Wright, K.
Haase, S.
Mohring, F.
Najer, A.
Henshall, I.
Ashdown, G.
Bannister, L.
Drew, D.
Beeson, J.
Fleck, R.
Moon, R.
Wilson, D.
Baum, J.
Citation: Scientific Reports, 2018; 8(1):10165-1-10165-11
Publisher: Nature Publishing Group
Issue Date: 2018
ISSN: 2045-2322
2045-2322
Statement of
Responsibility: 
Oliver Lyth, Gema Vizcay-Barrena, Katherine E. Wright, Silvia Haase, Franziska Mohring, Adrian Najer, Isabelle G. Henshall, George W. Ashdown, Lawrence H. Bannister, Damien R. Drew, James G. Beeson, Roland A. Fleck, Robert W. Moon, Danny W. Wilson and Jake Baum
Abstract: Plasmodium knowlesi, a zoonotic parasite causing severe-to-lethal malaria disease in humans, has only recently been adapted to continuous culture with human red blood cells (RBCs). In comparison with the most virulent human malaria, Plasmodium falciparum, there are, however, few cellular tools available to study its biology, in particular direct investigation of RBC invasion by blood-stage P. knowlesi merozoites. This leaves our current understanding of biological differences across pathogenic Plasmodium spp. incomplete. Here, we report a robust method for isolating viable and invasive P. knowlesi merozoites to high purity and yield. Using this approach, we present detailed comparative dissection of merozoite invasion (using a variety of microscopy platforms) and direct assessment of kinetic differences between knowlesi and falciparum merozoites. We go on to assess the inhibitory potential of molecules targeting discrete steps of invasion in either species via a quantitative invasion inhibition assay, identifying a class of polysulfonate polymer able to efficiently inhibit invasion in both, providing a foundation for pan-Plasmodium merozoite inhibitor development. Given the close evolutionary relationship between P. knowlesi and P. vivax, the second leading cause of malariarelated morbidity, this study paves the way for inter-specific dissection of invasion by all three major pathogenic malaria species.
Description: Published online: 05 July 2018
Rights: © The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
RMID: 0030094375
DOI: 10.1038/s41598-018-28457-z
Grant ID: http://purl.org/au-research/grants/nhmrc/1035715
Appears in Collections:Molecular and Biomedical Science publications

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