The Plasmodium falciparum male gametocyte protein P230p, a paralog of P230, is vital for ookinete formation and mosquito transmission

Catherin Marin-Mogollon, Marga van de Vegte-Bolmer, Geert Jan van Gemert, Fiona J.A. van Pul, Jai Ramesar, Ahmad Syibli Othman, Hans Kroeze, Jun Miao, Liwang Cui, Kim C. Williamson, Robert W. Sauerwein, Chris J. Janse, Shahid M. Khan

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Two members of 6-cysteine (6-cys) protein family, P48/45 and P230, are important for gamete fertility in rodent and human malaria parasites and are leading transmission blocking vaccine antigens. Rodent and human parasites encode a paralog of P230, called P230p. While P230 is expressed in male and female parasites, P230p is expressed only in male gametocytes and gametes. In rodent malaria parasites this protein is dispensable throughout the complete life-cycle; however, its function in P. falciparum is unknown. Using CRISPR/Cas9 methodology we disrupted the gene encoding Pfp230p resulting in P. falciparum mutants (PfΔp230p) lacking P230p expression. The PfΔp230p mutants produced normal numbers of male and female gametocytes, which retained expression of P48/45 and P230. Upon activation male PfΔp230p gametocytes undergo exflagellation and form male gametes. However, male gametes are unable to attach to red blood cells resulting in the absence of characteristic exflagellation centres in vitro. In the absence of P230p, zygote formation as well as oocyst and sporozoite development were strongly reduced (>98%) in mosquitoes. These observations demonstrate that P230p, like P230 and P48/45, has a vital role in P. falciparum male fertility and zygote formation and warrants further investigation as a potential transmission blocking vaccine candidate.

Original languageEnglish (US)
Article number14902
JournalScientific reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Plasmodium falciparum
Culicidae
Germ Cells
Parasites
Proteins
Rodentia
Zygote
Malaria
Fertility
Vaccines
Clustered Regularly Interspaced Short Palindromic Repeats
Sporozoites
Oocysts
p 230
Life Cycle Stages
Cysteine
Erythrocytes
Antigens
Genes

All Science Journal Classification (ASJC) codes

  • General

Cite this

Marin-Mogollon, C., van de Vegte-Bolmer, M., van Gemert, G. J., van Pul, F. J. A., Ramesar, J., Othman, A. S., ... Khan, S. M. (2018). The Plasmodium falciparum male gametocyte protein P230p, a paralog of P230, is vital for ookinete formation and mosquito transmission. Scientific reports, 8(1), [14902]. https://doi.org/10.1038/s41598-018-33236-x
Marin-Mogollon, Catherin ; van de Vegte-Bolmer, Marga ; van Gemert, Geert Jan ; van Pul, Fiona J.A. ; Ramesar, Jai ; Othman, Ahmad Syibli ; Kroeze, Hans ; Miao, Jun ; Cui, Liwang ; Williamson, Kim C. ; Sauerwein, Robert W. ; Janse, Chris J. ; Khan, Shahid M. / The Plasmodium falciparum male gametocyte protein P230p, a paralog of P230, is vital for ookinete formation and mosquito transmission. In: Scientific reports. 2018 ; Vol. 8, No. 1.
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abstract = "Two members of 6-cysteine (6-cys) protein family, P48/45 and P230, are important for gamete fertility in rodent and human malaria parasites and are leading transmission blocking vaccine antigens. Rodent and human parasites encode a paralog of P230, called P230p. While P230 is expressed in male and female parasites, P230p is expressed only in male gametocytes and gametes. In rodent malaria parasites this protein is dispensable throughout the complete life-cycle; however, its function in P. falciparum is unknown. Using CRISPR/Cas9 methodology we disrupted the gene encoding Pfp230p resulting in P. falciparum mutants (PfΔp230p) lacking P230p expression. The PfΔp230p mutants produced normal numbers of male and female gametocytes, which retained expression of P48/45 and P230. Upon activation male PfΔp230p gametocytes undergo exflagellation and form male gametes. However, male gametes are unable to attach to red blood cells resulting in the absence of characteristic exflagellation centres in vitro. In the absence of P230p, zygote formation as well as oocyst and sporozoite development were strongly reduced (>98{\%}) in mosquitoes. These observations demonstrate that P230p, like P230 and P48/45, has a vital role in P. falciparum male fertility and zygote formation and warrants further investigation as a potential transmission blocking vaccine candidate.",
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Marin-Mogollon, C, van de Vegte-Bolmer, M, van Gemert, GJ, van Pul, FJA, Ramesar, J, Othman, AS, Kroeze, H, Miao, J, Cui, L, Williamson, KC, Sauerwein, RW, Janse, CJ & Khan, SM 2018, 'The Plasmodium falciparum male gametocyte protein P230p, a paralog of P230, is vital for ookinete formation and mosquito transmission', Scientific reports, vol. 8, no. 1, 14902. https://doi.org/10.1038/s41598-018-33236-x

The Plasmodium falciparum male gametocyte protein P230p, a paralog of P230, is vital for ookinete formation and mosquito transmission. / Marin-Mogollon, Catherin; van de Vegte-Bolmer, Marga; van Gemert, Geert Jan; van Pul, Fiona J.A.; Ramesar, Jai; Othman, Ahmad Syibli; Kroeze, Hans; Miao, Jun; Cui, Liwang; Williamson, Kim C.; Sauerwein, Robert W.; Janse, Chris J.; Khan, Shahid M.

In: Scientific reports, Vol. 8, No. 1, 14902, 01.12.2018.

Research output: Contribution to journalArticle

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T1 - The Plasmodium falciparum male gametocyte protein P230p, a paralog of P230, is vital for ookinete formation and mosquito transmission

AU - Marin-Mogollon, Catherin

AU - van de Vegte-Bolmer, Marga

AU - van Gemert, Geert Jan

AU - van Pul, Fiona J.A.

AU - Ramesar, Jai

AU - Othman, Ahmad Syibli

AU - Kroeze, Hans

AU - Miao, Jun

AU - Cui, Liwang

AU - Williamson, Kim C.

AU - Sauerwein, Robert W.

AU - Janse, Chris J.

AU - Khan, Shahid M.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Two members of 6-cysteine (6-cys) protein family, P48/45 and P230, are important for gamete fertility in rodent and human malaria parasites and are leading transmission blocking vaccine antigens. Rodent and human parasites encode a paralog of P230, called P230p. While P230 is expressed in male and female parasites, P230p is expressed only in male gametocytes and gametes. In rodent malaria parasites this protein is dispensable throughout the complete life-cycle; however, its function in P. falciparum is unknown. Using CRISPR/Cas9 methodology we disrupted the gene encoding Pfp230p resulting in P. falciparum mutants (PfΔp230p) lacking P230p expression. The PfΔp230p mutants produced normal numbers of male and female gametocytes, which retained expression of P48/45 and P230. Upon activation male PfΔp230p gametocytes undergo exflagellation and form male gametes. However, male gametes are unable to attach to red blood cells resulting in the absence of characteristic exflagellation centres in vitro. In the absence of P230p, zygote formation as well as oocyst and sporozoite development were strongly reduced (>98%) in mosquitoes. These observations demonstrate that P230p, like P230 and P48/45, has a vital role in P. falciparum male fertility and zygote formation and warrants further investigation as a potential transmission blocking vaccine candidate.

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