The Vacuolar Zinc Transporter TgZnT Protects <named-content content-type="genus-species">Toxoplasma gondii</named-content> from Zinc Toxicity

ABSTRACT Zinc (Zn2+) is the most abundant biological metal ion aside from iron and is an essential element in numerous biological systems, acting as a cofactor for a large number of enzymes and regulatory proteins. Zn2+ must be tightly regulated, as both the deficiency and overabundance of intracell...

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Autores principales:	Nathan M. Chasen, Andrew J. Stasic, Beejan Asady, Isabelle Coppens, Silvia N. J. Moreno
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Toxoplasma gondii zinc transport transporters Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/5147ce4ee9484ff38aedf9457da77216
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spelling	oai:doaj.org-article:5147ce4ee9484ff38aedf9457da772162021-11-15T15:22:20ZThe Vacuolar Zinc Transporter TgZnT Protects <named-content content-type="genus-species">Toxoplasma gondii</named-content> from Zinc Toxicity10.1128/mSphere.00086-192379-5042https://doaj.org/article/5147ce4ee9484ff38aedf9457da772162019-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00086-19https://doaj.org/toc/2379-5042ABSTRACT Zinc (Zn2+) is the most abundant biological metal ion aside from iron and is an essential element in numerous biological systems, acting as a cofactor for a large number of enzymes and regulatory proteins. Zn2+ must be tightly regulated, as both the deficiency and overabundance of intracellular free Zn2+ are harmful to cells. Zn2+ transporters (ZnTs) play important functions in cells by reducing intracellular Zn2+ levels by transporting the ion out of the cytoplasm. We characterized a Toxoplasma gondii gene (TgGT1_251630, TgZnT), which is annotated as the only ZnT family Zn2+ transporter in T. gondii. TgZnT localizes to novel vesicles that fuse with the plant-like vacuole (PLV), an endosome-like organelle. Mutant parasites lacking TgZnT exhibit reduced viability in in vitro assays. This phenotype was exacerbated by increasing zinc concentrations in the extracellular media and was rescued by media with reduced zinc. Heterologous expression of TgZnT in a Zn2+-sensitive Saccharomyces cerevisiae yeast strain partially restored growth in media with higher Zn2+ concentrations. These results suggest that TgZnT transports Zn2+ into the PLV and plays an important role in the Zn2+ tolerance of T. gondii extracellular tachyzoites. IMPORTANCE Toxoplasma gondii is an intracellular pathogen of human and animals. T. gondii pathogenesis is associated with its lytic cycle, which involves invasion, replication, egress out of the host cell, and invasion of a new one. T. gondii must be able to tolerate abrupt changes in the composition of the surrounding milieu as it progresses through its lytic cycle. We report the characterization of a Zn2+ transporter of T. gondii (TgZnT) that is important for parasite growth. TgZnT restored Zn2+ tolerance in yeast mutants that were unable to grow in media with high concentrations of Zn2+. We propose that TgZnT plays a role in Zn2+ homeostasis during the T. gondii lytic cycle.Nathan M. ChasenAndrew J. StasicBeejan AsadyIsabelle CoppensSilvia N. J. MorenoAmerican Society for MicrobiologyarticleToxoplasma gondiizinc transporttransportersMicrobiologyQR1-502ENmSphere, Vol 4, Iss 3 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Toxoplasma gondii zinc transport transporters Microbiology QR1-502
spellingShingle	Toxoplasma gondii zinc transport transporters Microbiology QR1-502 Nathan M. Chasen Andrew J. Stasic Beejan Asady Isabelle Coppens Silvia N. J. Moreno The Vacuolar Zinc Transporter TgZnT Protects <named-content content-type="genus-species">Toxoplasma gondii</named-content> from Zinc Toxicity
description	ABSTRACT Zinc (Zn2+) is the most abundant biological metal ion aside from iron and is an essential element in numerous biological systems, acting as a cofactor for a large number of enzymes and regulatory proteins. Zn2+ must be tightly regulated, as both the deficiency and overabundance of intracellular free Zn2+ are harmful to cells. Zn2+ transporters (ZnTs) play important functions in cells by reducing intracellular Zn2+ levels by transporting the ion out of the cytoplasm. We characterized a Toxoplasma gondii gene (TgGT1_251630, TgZnT), which is annotated as the only ZnT family Zn2+ transporter in T. gondii. TgZnT localizes to novel vesicles that fuse with the plant-like vacuole (PLV), an endosome-like organelle. Mutant parasites lacking TgZnT exhibit reduced viability in in vitro assays. This phenotype was exacerbated by increasing zinc concentrations in the extracellular media and was rescued by media with reduced zinc. Heterologous expression of TgZnT in a Zn2+-sensitive Saccharomyces cerevisiae yeast strain partially restored growth in media with higher Zn2+ concentrations. These results suggest that TgZnT transports Zn2+ into the PLV and plays an important role in the Zn2+ tolerance of T. gondii extracellular tachyzoites. IMPORTANCE Toxoplasma gondii is an intracellular pathogen of human and animals. T. gondii pathogenesis is associated with its lytic cycle, which involves invasion, replication, egress out of the host cell, and invasion of a new one. T. gondii must be able to tolerate abrupt changes in the composition of the surrounding milieu as it progresses through its lytic cycle. We report the characterization of a Zn2+ transporter of T. gondii (TgZnT) that is important for parasite growth. TgZnT restored Zn2+ tolerance in yeast mutants that were unable to grow in media with high concentrations of Zn2+. We propose that TgZnT plays a role in Zn2+ homeostasis during the T. gondii lytic cycle.
format	article
author	Nathan M. Chasen Andrew J. Stasic Beejan Asady Isabelle Coppens Silvia N. J. Moreno
author_facet	Nathan M. Chasen Andrew J. Stasic Beejan Asady Isabelle Coppens Silvia N. J. Moreno
author_sort	Nathan M. Chasen
title	The Vacuolar Zinc Transporter TgZnT Protects <named-content content-type="genus-species">Toxoplasma gondii</named-content> from Zinc Toxicity
title_short	The Vacuolar Zinc Transporter TgZnT Protects <named-content content-type="genus-species">Toxoplasma gondii</named-content> from Zinc Toxicity
title_full	The Vacuolar Zinc Transporter TgZnT Protects <named-content content-type="genus-species">Toxoplasma gondii</named-content> from Zinc Toxicity
title_fullStr	The Vacuolar Zinc Transporter TgZnT Protects <named-content content-type="genus-species">Toxoplasma gondii</named-content> from Zinc Toxicity
title_full_unstemmed	The Vacuolar Zinc Transporter TgZnT Protects <named-content content-type="genus-species">Toxoplasma gondii</named-content> from Zinc Toxicity
title_sort	vacuolar zinc transporter tgznt protects <named-content content-type="genus-species">toxoplasma gondii</named-content> from zinc toxicity
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/5147ce4ee9484ff38aedf9457da77216
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The Vacuolar Zinc Transporter TgZnT Protects <named-content content-type="genus-species">Toxoplasma gondii</named-content> from Zinc Toxicity

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