Identifying the major lactate transporter of Toxoplasma gondii tachyzoites

Abstract Toxoplasma gondii and Plasmodium falciparum parasites both extrude l-lactate, a byproduct of glycolysis. The P. falciparum Formate Nitrite Transporter, PfFNT, mediates l-lactate transport across the plasma membrane of P. falciparum parasites and has been validated as a drug target. The T. g...

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Autores principales:	Joy M. Zeng, Sanduni V. Hapuarachchi, Sarah H. Shafik, Rowena E. Martin, Kiaran Kirk, Giel G. van Dooren, Adele M. Lehane
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2487d4ef217541f185f3c2fd767c2794
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spelling	oai:doaj.org-article:2487d4ef217541f185f3c2fd767c27942021-12-02T14:02:55ZIdentifying the major lactate transporter of Toxoplasma gondii tachyzoites10.1038/s41598-021-86204-32045-2322https://doaj.org/article/2487d4ef217541f185f3c2fd767c27942021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86204-3https://doaj.org/toc/2045-2322Abstract Toxoplasma gondii and Plasmodium falciparum parasites both extrude l-lactate, a byproduct of glycolysis. The P. falciparum Formate Nitrite Transporter, PfFNT, mediates l-lactate transport across the plasma membrane of P. falciparum parasites and has been validated as a drug target. The T. gondii genome encodes three FNTs that have been shown to transport l-lactate, and which are proposed to be the targets of several inhibitors of T. gondii proliferation. Here, we show that each of the TgFNTs localize to the T. gondii plasma membrane and are capable of transporting l-lactate across it, with TgFNT1 making the primary contribution to l-lactate transport during the disease-causing lytic cycle of the parasite. We use the Xenopus oocyte expression system to provide direct measurements of l-lactate transport via TgFNT1. We undertake a genetic analysis of the importance of the tgfnt genes for parasite proliferation, and demonstrate that all three tgfnt genes can be disrupted individually and together without affecting the lytic cycle under in vitro culture conditions. Together, our experiments identify the major lactate transporter in the disease causing stage of T. gondii, and reveal that this transporter is not required for parasite proliferation, indicating that TgFNTs are unlikely to be targets for anti-Toxoplasma drugs.Joy M. ZengSanduni V. HapuarachchiSarah H. ShafikRowena E. MartinKiaran KirkGiel G. van DoorenAdele M. LehaneNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Joy M. Zeng Sanduni V. Hapuarachchi Sarah H. Shafik Rowena E. Martin Kiaran Kirk Giel G. van Dooren Adele M. Lehane Identifying the major lactate transporter of Toxoplasma gondii tachyzoites
description	Abstract Toxoplasma gondii and Plasmodium falciparum parasites both extrude l-lactate, a byproduct of glycolysis. The P. falciparum Formate Nitrite Transporter, PfFNT, mediates l-lactate transport across the plasma membrane of P. falciparum parasites and has been validated as a drug target. The T. gondii genome encodes three FNTs that have been shown to transport l-lactate, and which are proposed to be the targets of several inhibitors of T. gondii proliferation. Here, we show that each of the TgFNTs localize to the T. gondii plasma membrane and are capable of transporting l-lactate across it, with TgFNT1 making the primary contribution to l-lactate transport during the disease-causing lytic cycle of the parasite. We use the Xenopus oocyte expression system to provide direct measurements of l-lactate transport via TgFNT1. We undertake a genetic analysis of the importance of the tgfnt genes for parasite proliferation, and demonstrate that all three tgfnt genes can be disrupted individually and together without affecting the lytic cycle under in vitro culture conditions. Together, our experiments identify the major lactate transporter in the disease causing stage of T. gondii, and reveal that this transporter is not required for parasite proliferation, indicating that TgFNTs are unlikely to be targets for anti-Toxoplasma drugs.
format	article
author	Joy M. Zeng Sanduni V. Hapuarachchi Sarah H. Shafik Rowena E. Martin Kiaran Kirk Giel G. van Dooren Adele M. Lehane
author_facet	Joy M. Zeng Sanduni V. Hapuarachchi Sarah H. Shafik Rowena E. Martin Kiaran Kirk Giel G. van Dooren Adele M. Lehane
author_sort	Joy M. Zeng
title	Identifying the major lactate transporter of Toxoplasma gondii tachyzoites
title_short	Identifying the major lactate transporter of Toxoplasma gondii tachyzoites
title_full	Identifying the major lactate transporter of Toxoplasma gondii tachyzoites
title_fullStr	Identifying the major lactate transporter of Toxoplasma gondii tachyzoites
title_full_unstemmed	Identifying the major lactate transporter of Toxoplasma gondii tachyzoites
title_sort	identifying the major lactate transporter of toxoplasma gondii tachyzoites
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2487d4ef217541f185f3c2fd767c2794
work_keys_str_mv	AT joymzeng identifyingthemajorlactatetransporteroftoxoplasmagondiitachyzoites AT sandunivhapuarachchi identifyingthemajorlactatetransporteroftoxoplasmagondiitachyzoites AT sarahhshafik identifyingthemajorlactatetransporteroftoxoplasmagondiitachyzoites AT rowenaemartin identifyingthemajorlactatetransporteroftoxoplasmagondiitachyzoites AT kiarankirk identifyingthemajorlactatetransporteroftoxoplasmagondiitachyzoites AT gielgvandooren identifyingthemajorlactatetransporteroftoxoplasmagondiitachyzoites AT adelemlehane identifyingthemajorlactatetransporteroftoxoplasmagondiitachyzoites
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Identifying the major lactate transporter of Toxoplasma gondii tachyzoites

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