Normocyte-binding protein required for human erythrocyte invasion by the zoonotic malaria parasitePlasmodium knowlesi

Robert W. Moon; Hazem Sharaf; Claire H. Hastings; Ho Shwen; Mridul Nair; ‍Zineb Rchiad; Ellen Knuepfer; Abhinay Ramaprasad; Franziska Mohring; Amirah Amir; Noor A. Yusuf; Joanna Hall; Neil Almond; Yee Ling Lau; Arnab Pain; Michael J. Blackman; Anthony A. Holder

doi:10.1073/pnas.1522469113

Normocyte-binding protein required for human erythrocyte invasion by the zoonotic malaria parasitePlasmodium knowlesi

Robert W. Moon, Hazem Sharaf, Claire H. Hastings, Ho Shwen, Mridul Nair, ‍Zineb Rchiad, Ellen Knuepfer, Abhinay Ramaprasad, Franziska Mohring, Amirah Amir, Noor A. Yusuf, Joanna Hall, Neil Almond, Yee Ling Lau, Arnab Pain, Michael J. Blackman, Anthony A. Holder

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Abstract

The dominant cause of malaria in Malaysia is now Plasmodium knowlesi, a zoonotic parasite of cynomolgus macaque monkeys found throughout South East Asia. Comparative genomic analysis of parasites adapted to in vitro growth in either cynomolgus or human RBCs identified a genomic deletion that includes the gene encoding normocyte-binding protein Xa (NBPXa) in parasites growing in cynomolgus RBCs but not in human RBCs. Experimental deletion of the NBPXa gene in parasites adapted to growth in human RBCs (which retain the ability to grow in cynomolgus RBCs) restricted them to cynomolgus RBCs, demonstrating that this gene is selectively required for parasite multiplication and growth in human RBCs. NBPXa-null parasites could bind to human RBCs, but invasion of these cells was severely impaired. Therefore, NBPXa is identified as a key mediator of P. knowlesi human infection and may be a target for vaccine development against this emerging pathogen.

Original language	English (US)
Pages (from-to)	7231-7236
Number of pages	6
Journal	Proceedings of the National Academy of Sciences
Volume	113
Issue number	26
DOIs	https://doi.org/10.1073/pnas.1522469113
State	Published - Jun 14 2016

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK, the UK Medical Research Council (MRC), and the Wellcome Trust. The work was further supported by the UK MRC (Grants U117532063 and U117532067), the European Community's Seventh Framework Programme under Grant Agreement 242095 (EviMalar), an MRC Career Development Award (to R.W.M.) jointly funded by the UK MRC and Department for International Development, and the faculty baseline fund (BRF) from the King Abdullah University of Science and Technology (to A.P.). A.A. and Y.L.L. were funded by a UM High Impact Research (HIR) Grant UM-MOHE (UM.C/HIR/MOHE/MED/16) from the Ministry of Higher Education Malaysia.

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10.1073/pnas.1522469113

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Moon, R. W., Sharaf, H., Hastings, C. H., Shwen, H., Nair, M., Rchiad, Z., Knuepfer, E., Ramaprasad, A., Mohring, F., Amir, A., Yusuf, N. A., Hall, J., Almond, N., Lau, Y. L., Pain, A., Blackman, M. J., & Holder, A. A. (2016). Normocyte-binding protein required for human erythrocyte invasion by the zoonotic malaria parasitePlasmodium knowlesi. Proceedings of the National Academy of Sciences, 113(26), 7231-7236. https://doi.org/10.1073/pnas.1522469113

@article{d48e5a9ec8fe41b185a59e01c9e19214,

title = "Normocyte-binding protein required for human erythrocyte invasion by the zoonotic malaria parasitePlasmodium knowlesi",

abstract = "The dominant cause of malaria in Malaysia is now Plasmodium knowlesi, a zoonotic parasite of cynomolgus macaque monkeys found throughout South East Asia. Comparative genomic analysis of parasites adapted to in vitro growth in either cynomolgus or human RBCs identified a genomic deletion that includes the gene encoding normocyte-binding protein Xa (NBPXa) in parasites growing in cynomolgus RBCs but not in human RBCs. Experimental deletion of the NBPXa gene in parasites adapted to growth in human RBCs (which retain the ability to grow in cynomolgus RBCs) restricted them to cynomolgus RBCs, demonstrating that this gene is selectively required for parasite multiplication and growth in human RBCs. NBPXa-null parasites could bind to human RBCs, but invasion of these cells was severely impaired. Therefore, NBPXa is identified as a key mediator of P. knowlesi human infection and may be a target for vaccine development against this emerging pathogen.",

author = "Moon, {Robert W.} and Hazem Sharaf and Hastings, {Claire H.} and Ho Shwen and Mridul Nair and ‍Zineb Rchiad and Ellen Knuepfer and Abhinay Ramaprasad and Franziska Mohring and Amirah Amir and Yusuf, {Noor A.} and Joanna Hall and Neil Almond and Lau, {Yee Ling} and Arnab Pain and Blackman, {Michael J.} and Holder, {Anthony A.}",

note = "KAUST Repository Item: Exported on 2020-10-01 Acknowledgements: This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK, the UK Medical Research Council (MRC), and the Wellcome Trust. The work was further supported by the UK MRC (Grants U117532063 and U117532067), the European Community's Seventh Framework Programme under Grant Agreement 242095 (EviMalar), an MRC Career Development Award (to R.W.M.) jointly funded by the UK MRC and Department for International Development, and the faculty baseline fund (BRF) from the King Abdullah University of Science and Technology (to A.P.). A.A. and Y.L.L. were funded by a UM High Impact Research (HIR) Grant UM-MOHE (UM.C/HIR/MOHE/MED/16) from the Ministry of Higher Education Malaysia.",

year = "2016",

month = jun,

day = "14",

doi = "10.1073/pnas.1522469113",

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Moon, RW, Sharaf, H, Hastings, CH, Shwen, H, Nair, M, Rchiad, Z, Knuepfer, E, Ramaprasad, A, Mohring, F, Amir, A, Yusuf, NA, Hall, J, Almond, N, Lau, YL, Pain, A, Blackman, MJ & Holder, AA 2016, 'Normocyte-binding protein required for human erythrocyte invasion by the zoonotic malaria parasitePlasmodium knowlesi', Proceedings of the National Academy of Sciences, vol. 113, no. 26, pp. 7231-7236. https://doi.org/10.1073/pnas.1522469113

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T1 - Normocyte-binding protein required for human erythrocyte invasion by the zoonotic malaria parasitePlasmodium knowlesi

AU - Moon, Robert W.

AU - Sharaf, Hazem

AU - Hastings, Claire H.

AU - Shwen, Ho

AU - Nair, Mridul

AU - Rchiad, ‍Zineb

AU - Knuepfer, Ellen

AU - Ramaprasad, Abhinay

AU - Mohring, Franziska

AU - Amir, Amirah

AU - Yusuf, Noor A.

AU - Hall, Joanna

AU - Almond, Neil

AU - Lau, Yee Ling

AU - Pain, Arnab

AU - Blackman, Michael J.

AU - Holder, Anthony A.

N1 - KAUST Repository Item: Exported on 2020-10-01 Acknowledgements: This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK, the UK Medical Research Council (MRC), and the Wellcome Trust. The work was further supported by the UK MRC (Grants U117532063 and U117532067), the European Community's Seventh Framework Programme under Grant Agreement 242095 (EviMalar), an MRC Career Development Award (to R.W.M.) jointly funded by the UK MRC and Department for International Development, and the faculty baseline fund (BRF) from the King Abdullah University of Science and Technology (to A.P.). A.A. and Y.L.L. were funded by a UM High Impact Research (HIR) Grant UM-MOHE (UM.C/HIR/MOHE/MED/16) from the Ministry of Higher Education Malaysia.

PY - 2016/6/14

Y1 - 2016/6/14

N2 - The dominant cause of malaria in Malaysia is now Plasmodium knowlesi, a zoonotic parasite of cynomolgus macaque monkeys found throughout South East Asia. Comparative genomic analysis of parasites adapted to in vitro growth in either cynomolgus or human RBCs identified a genomic deletion that includes the gene encoding normocyte-binding protein Xa (NBPXa) in parasites growing in cynomolgus RBCs but not in human RBCs. Experimental deletion of the NBPXa gene in parasites adapted to growth in human RBCs (which retain the ability to grow in cynomolgus RBCs) restricted them to cynomolgus RBCs, demonstrating that this gene is selectively required for parasite multiplication and growth in human RBCs. NBPXa-null parasites could bind to human RBCs, but invasion of these cells was severely impaired. Therefore, NBPXa is identified as a key mediator of P. knowlesi human infection and may be a target for vaccine development against this emerging pathogen.

AB - The dominant cause of malaria in Malaysia is now Plasmodium knowlesi, a zoonotic parasite of cynomolgus macaque monkeys found throughout South East Asia. Comparative genomic analysis of parasites adapted to in vitro growth in either cynomolgus or human RBCs identified a genomic deletion that includes the gene encoding normocyte-binding protein Xa (NBPXa) in parasites growing in cynomolgus RBCs but not in human RBCs. Experimental deletion of the NBPXa gene in parasites adapted to growth in human RBCs (which retain the ability to grow in cynomolgus RBCs) restricted them to cynomolgus RBCs, demonstrating that this gene is selectively required for parasite multiplication and growth in human RBCs. NBPXa-null parasites could bind to human RBCs, but invasion of these cells was severely impaired. Therefore, NBPXa is identified as a key mediator of P. knowlesi human infection and may be a target for vaccine development against this emerging pathogen.

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DO - 10.1073/pnas.1522469113

M3 - Article

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VL - 113

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EP - 7236

JO - Proceedings of the National Academy of Sciences

JF - Proceedings of the National Academy of Sciences

IS - 26

ER -

Normocyte-binding protein required for human erythrocyte invasion by the zoonotic malaria parasitePlasmodium knowlesi

Abstract

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