Cellular dissection of malaria parasite invasion of human erythrocytes using viable Plasmodium knowlesi merozoites

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, Jake Baum

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

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 malaria-related morbidity, this study paves the way for inter-specific dissection of invasion by all three major pathogenic malaria species.

Original languageEnglish
Article number10165
Number of pages11
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 5 Jul 2018

Keywords

  • cell biology
  • parasite biology

Cite this

Lyth, O., Vizcay-Barrena, G., Wright, K. E., Haase, S., Mohring, F., Najer, A., ... Baum, J. (2018). Cellular dissection of malaria parasite invasion of human erythrocytes using viable Plasmodium knowlesi merozoites. Scientific Reports, 8(1), [10165]. https://doi.org/10.1038/s41598-018-28457-z
Lyth, Oliver ; Vizcay-Barrena, Gema ; Wright, Katherine E. ; Haase, Silvia ; Mohring, Franziska ; Najer, Adrian ; Henshall, Isabelle G. ; Ashdown, George W. ; Bannister, Lawrence H. ; Drew, Damien R. ; Beeson, James G. ; Fleck, Roland A. ; Moon, Robert W. ; Wilson, Danny W. ; Baum, Jake. / Cellular dissection of malaria parasite invasion of human erythrocytes using viable Plasmodium knowlesi merozoites. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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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 malaria-related morbidity, this study paves the way for inter-specific dissection of invasion by all three major pathogenic malaria species.",
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author = "Oliver Lyth and Gema Vizcay-Barrena and Wright, {Katherine E.} and Silvia Haase and Franziska Mohring and Adrian Najer and Henshall, {Isabelle G.} and Ashdown, {George W.} and Bannister, {Lawrence H.} and Drew, {Damien R.} and Beeson, {James G.} and Fleck, {Roland A.} and Moon, {Robert W.} and Wilson, {Danny W.} and Jake Baum",
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Lyth, O, Vizcay-Barrena, G, Wright, KE, Haase, S, Mohring, F, Najer, A, Henshall, IG, Ashdown, GW, Bannister, LH, Drew, DR, Beeson, JG, Fleck, RA, Moon, RW, Wilson, DW & Baum, J 2018, 'Cellular dissection of malaria parasite invasion of human erythrocytes using viable Plasmodium knowlesi merozoites', Scientific Reports, vol. 8, no. 1, 10165. https://doi.org/10.1038/s41598-018-28457-z

Cellular dissection of malaria parasite invasion of human erythrocytes using viable Plasmodium knowlesi merozoites. / Lyth, Oliver; Vizcay-Barrena, Gema; Wright, Katherine E.; Haase, Silvia; Mohring, Franziska; Najer, Adrian; Henshall, Isabelle G.; Ashdown, George W.; Bannister, Lawrence H.; Drew, Damien R.; Beeson, James G.; Fleck, Roland A.; Moon, Robert W.; Wilson, Danny W.; Baum, Jake.

In: Scientific Reports, Vol. 8, No. 1, 10165, 05.07.2018.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Lyth, Oliver

AU - Vizcay-Barrena, Gema

AU - Wright, Katherine E.

AU - Haase, Silvia

AU - Mohring, Franziska

AU - Najer, Adrian

AU - Henshall, Isabelle G.

AU - Ashdown, George W.

AU - Bannister, Lawrence H.

AU - Drew, Damien R.

AU - Beeson, James G.

AU - Fleck, Roland A.

AU - Moon, Robert W.

AU - Wilson, Danny W.

AU - Baum, Jake

PY - 2018/7/5

Y1 - 2018/7/5

N2 - 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 malaria-related morbidity, this study paves the way for inter-specific dissection of invasion by all three major pathogenic malaria species.

AB - 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 malaria-related morbidity, this study paves the way for inter-specific dissection of invasion by all three major pathogenic malaria species.

KW - cell biology

KW - parasite biology

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