Rapid identification of genes controlling virulence and immunity in malaria parasites

Hussein M. Abkallo; Axel Martinelli; Megumi Inoue; Abhinay Ramaprasad; Phonepadith Xangsayarath; Jesse Gitaka; Jianxia Tang; Kazuhide Yahata; Augustin Zoungrana; Hayato Mitaka; Arita Acharjee; Partha P. Datta; Paul Hunt; Richard Carter; Osamu Kaneko; Ville Mustonen; Christopher J. R. Illingworth; Arnab Pain; Richard Culleton

doi:10.1371/journal.ppat.1006447

Rapid identification of genes controlling virulence and immunity in malaria parasites

Hussein M. Abkallo, Axel Martinelli, Megumi Inoue, Abhinay Ramaprasad, Phonepadith Xangsayarath, Jesse Gitaka, Jianxia Tang, Kazuhide Yahata, Augustin Zoungrana, Hayato Mitaka, Arita Acharjee, Partha P. Datta, Paul Hunt, Richard Carter, Osamu Kaneko, Ville Mustonen, Christopher J. R. Illingworth, Arnab Pain, Richard Culleton

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Abstract

Identifying the genetic determinants of phenotypes that impact disease severity is of fundamental importance for the design of new interventions against malaria. Here we present a rapid genome-wide approach capable of identifying multiple genetic drivers of medically relevant phenotypes within malaria parasites via a single experiment at single gene or allele resolution. In a proof of principle study, we found that a previously undescribed single nucleotide polymorphism in the binding domain of the erythrocyte binding like protein (EBL) conferred a dramatic change in red blood cell invasion in mutant rodent malaria parasites Plasmodium yoelii. In the same experiment, we implicated merozoite surface protein 1 (MSP1) and other polymorphic proteins, as the major targets of strain-specific immunity. Using allelic replacement, we provide functional validation of the substitution in the EBL gene controlling the growth rate in the blood stages of the parasites.

Original language	English (US)
Pages (from-to)	e1006447
Journal	PLOS Pathogens
Volume	13
Issue number	7
DOIs	https://doi.org/10.1371/journal.ppat.1006447
State	Published - Jul 12 2017

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https://repository.kaust.edu.sa/bitstream/10754/625229/1/journal.ppat.1006447.pdf

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Abkallo, H. M., Martinelli, A., Inoue, M., Ramaprasad, A., Xangsayarath, P., Gitaka, J., Tang, J., Yahata, K., Zoungrana, A., Mitaka, H., Acharjee, A., Datta, P. P., Hunt, P., Carter, R., Kaneko, O., Mustonen, V., Illingworth, C. J. R., Pain, A., & Culleton, R. (2017). Rapid identification of genes controlling virulence and immunity in malaria parasites. PLOS Pathogens, 13(7), e1006447. https://doi.org/10.1371/journal.ppat.1006447

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title = "Rapid identification of genes controlling virulence and immunity in malaria parasites",

abstract = "Identifying the genetic determinants of phenotypes that impact disease severity is of fundamental importance for the design of new interventions against malaria. Here we present a rapid genome-wide approach capable of identifying multiple genetic drivers of medically relevant phenotypes within malaria parasites via a single experiment at single gene or allele resolution. In a proof of principle study, we found that a previously undescribed single nucleotide polymorphism in the binding domain of the erythrocyte binding like protein (EBL) conferred a dramatic change in red blood cell invasion in mutant rodent malaria parasites Plasmodium yoelii. In the same experiment, we implicated merozoite surface protein 1 (MSP1) and other polymorphic proteins, as the major targets of strain-specific immunity. Using allelic replacement, we provide functional validation of the substitution in the EBL gene controlling the growth rate in the blood stages of the parasites.",

author = "Abkallo, {Hussein M.} and Axel Martinelli and Megumi Inoue and Abhinay Ramaprasad and Phonepadith Xangsayarath and Jesse Gitaka and Jianxia Tang and Kazuhide Yahata and Augustin Zoungrana and Hayato Mitaka and Arita Acharjee and Datta, {Partha P.} and Paul Hunt and Richard Carter and Osamu Kaneko and Ville Mustonen and Illingworth, {Christopher J. R.} and Arnab Pain and Richard Culleton",

note = "KAUST Repository Item: Exported on 2020-10-01 Acknowledged KAUST grant number(s): BAS/1/1020-01-01 Acknowledgements: This work was supported by the JSPS (project numbers Nos. JP25870525, JP24255009 and JP16K21233) (to RCu), A Royal Society Bilateral Grant for Co-operative Research (to RCa and RCu) and a Sasakawa Foundation Butterfield Award (to RCu), faculty baseline fund (BAS/1/1020-01-01) from the King Abdullah University of Science and Technology (KAUST) to AP, and Grants-in-Aid for Scientific Research on Innovative Areas JR23117008 (to OK). CJRI was supported by a Sir Henry Dale Fellowship, jointly funded by the Wellcome Trust and the Royal Society (101239/Z/13/Z). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.",

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Abkallo, HM, Martinelli, A, Inoue, M, Ramaprasad, A, Xangsayarath, P, Gitaka, J, Tang, J, Yahata, K, Zoungrana, A, Mitaka, H, Acharjee, A, Datta, PP, Hunt, P, Carter, R, Kaneko, O, Mustonen, V, Illingworth, CJR, Pain, A & Culleton, R 2017, 'Rapid identification of genes controlling virulence and immunity in malaria parasites', PLOS Pathogens, vol. 13, no. 7, pp. e1006447. https://doi.org/10.1371/journal.ppat.1006447

TY - JOUR

T1 - Rapid identification of genes controlling virulence and immunity in malaria parasites

AU - Abkallo, Hussein M.

AU - Martinelli, Axel

AU - Inoue, Megumi

AU - Ramaprasad, Abhinay

AU - Xangsayarath, Phonepadith

AU - Gitaka, Jesse

AU - Tang, Jianxia

AU - Yahata, Kazuhide

AU - Zoungrana, Augustin

AU - Mitaka, Hayato

AU - Acharjee, Arita

AU - Datta, Partha P.

AU - Hunt, Paul

AU - Carter, Richard

AU - Kaneko, Osamu

AU - Mustonen, Ville

AU - Illingworth, Christopher J. R.

AU - Pain, Arnab

AU - Culleton, Richard

N1 - KAUST Repository Item: Exported on 2020-10-01 Acknowledged KAUST grant number(s): BAS/1/1020-01-01 Acknowledgements: This work was supported by the JSPS (project numbers Nos. JP25870525, JP24255009 and JP16K21233) (to RCu), A Royal Society Bilateral Grant for Co-operative Research (to RCa and RCu) and a Sasakawa Foundation Butterfield Award (to RCu), faculty baseline fund (BAS/1/1020-01-01) from the King Abdullah University of Science and Technology (KAUST) to AP, and Grants-in-Aid for Scientific Research on Innovative Areas JR23117008 (to OK). CJRI was supported by a Sir Henry Dale Fellowship, jointly funded by the Wellcome Trust and the Royal Society (101239/Z/13/Z). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

PY - 2017/7/12

Y1 - 2017/7/12

N2 - Identifying the genetic determinants of phenotypes that impact disease severity is of fundamental importance for the design of new interventions against malaria. Here we present a rapid genome-wide approach capable of identifying multiple genetic drivers of medically relevant phenotypes within malaria parasites via a single experiment at single gene or allele resolution. In a proof of principle study, we found that a previously undescribed single nucleotide polymorphism in the binding domain of the erythrocyte binding like protein (EBL) conferred a dramatic change in red blood cell invasion in mutant rodent malaria parasites Plasmodium yoelii. In the same experiment, we implicated merozoite surface protein 1 (MSP1) and other polymorphic proteins, as the major targets of strain-specific immunity. Using allelic replacement, we provide functional validation of the substitution in the EBL gene controlling the growth rate in the blood stages of the parasites.

AB - Identifying the genetic determinants of phenotypes that impact disease severity is of fundamental importance for the design of new interventions against malaria. Here we present a rapid genome-wide approach capable of identifying multiple genetic drivers of medically relevant phenotypes within malaria parasites via a single experiment at single gene or allele resolution. In a proof of principle study, we found that a previously undescribed single nucleotide polymorphism in the binding domain of the erythrocyte binding like protein (EBL) conferred a dramatic change in red blood cell invasion in mutant rodent malaria parasites Plasmodium yoelii. In the same experiment, we implicated merozoite surface protein 1 (MSP1) and other polymorphic proteins, as the major targets of strain-specific immunity. Using allelic replacement, we provide functional validation of the substitution in the EBL gene controlling the growth rate in the blood stages of the parasites.

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DO - 10.1371/journal.ppat.1006447

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SN - 1553-7374

VL - 13

SP - e1006447

JO - PLOS Pathogens

JF - PLOS Pathogens

IS - 7

ER -

Rapid identification of genes controlling virulence and immunity in malaria parasites

Abstract

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