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

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 m...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Male Gametocytes Ookinete Formation Mosquito Transmission Exflagellation Centres Oocysts Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f6a6dc9e3dd1401da1383751074d9b2e
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spelling	oai:doaj.org-article:f6a6dc9e3dd1401da1383751074d9b2e2021-12-02T15:08:04ZThe Plasmodium falciparum male gametocyte protein P230p, a paralog of P230, is vital for ookinete formation and mosquito transmission10.1038/s41598-018-33236-x2045-2322https://doaj.org/article/f6a6dc9e3dd1401da1383751074d9b2e2018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-33236-xhttps://doaj.org/toc/2045-2322Abstract 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.Catherin Marin-MogollonMarga van de Vegte-BolmerGeert-Jan van GemertFiona J. A. van PulJai RamesarAhmad Syibli OthmanHans KroezeJun MiaoLiwang CuiKim C. WilliamsonRobert W. SauerweinChris J. JanseShahid M. KhanNature PortfolioarticleMale GametocytesOokinete FormationMosquito TransmissionExflagellation CentresOocystsMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Male Gametocytes Ookinete Formation Mosquito Transmission Exflagellation Centres Oocysts Medicine R Science Q
spellingShingle	Male Gametocytes Ookinete Formation Mosquito Transmission Exflagellation Centres Oocysts Medicine R Science Q 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 The Plasmodium falciparum male gametocyte protein P230p, a paralog of P230, is vital for ookinete formation and mosquito transmission
description	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.
format	article
author	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
author_facet	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
author_sort	Catherin Marin-Mogollon
title	The Plasmodium falciparum male gametocyte protein P230p, a paralog of P230, is vital for ookinete formation and mosquito transmission
title_short	The Plasmodium falciparum male gametocyte protein P230p, a paralog of P230, is vital for ookinete formation and mosquito transmission
title_full	The Plasmodium falciparum male gametocyte protein P230p, a paralog of P230, is vital for ookinete formation and mosquito transmission
title_fullStr	The Plasmodium falciparum male gametocyte protein P230p, a paralog of P230, is vital for ookinete formation and mosquito transmission
title_full_unstemmed	The Plasmodium falciparum male gametocyte protein P230p, a paralog of P230, is vital for ookinete formation and mosquito transmission
title_sort	plasmodium falciparum male gametocyte protein p230p, a paralog of p230, is vital for ookinete formation and mosquito transmission
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/f6a6dc9e3dd1401da1383751074d9b2e
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The Plasmodium falciparum male gametocyte protein P230p, a paralog of P230, is vital for ookinete formation and mosquito transmission

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