<named-content content-type="genus-species">Toxoplasma gondii</named-content> Intravacuolar-Network-Associated Dense Granule Proteins Regulate Maturation of the Cyst Matrix and Cyst Wall

ABSTRACT Little is known regarding how the chronic Toxoplasma gondii cyst develops. Here, we investigated intravacuolar-network-associated dense granule (GRA) proteins GRA1, GRA2, GRA4, GRA6, GRA9, and GRA12 during cyst development in vitro after differentiation of the tachyzoite-stage parasitophoro...

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Autores principales:	Rebekah B. Guevara, Barbara A. Fox, Alejandra Falla, David J. Bzik
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Toxoplasma gondii cysts chronic infection cyst wall cyst matrix intravacuolar network Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/0dd4b654c23e49efa692482b7cda66d3
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spelling	oai:doaj.org-article:0dd4b654c23e49efa692482b7cda66d32021-11-15T15:27:33Z<named-content content-type="genus-species">Toxoplasma gondii</named-content> Intravacuolar-Network-Associated Dense Granule Proteins Regulate Maturation of the Cyst Matrix and Cyst Wall10.1128/mSphere.00487-192379-5042https://doaj.org/article/0dd4b654c23e49efa692482b7cda66d32019-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00487-19https://doaj.org/toc/2379-5042ABSTRACT Little is known regarding how the chronic Toxoplasma gondii cyst develops. Here, we investigated intravacuolar-network-associated dense granule (GRA) proteins GRA1, GRA2, GRA4, GRA6, GRA9, and GRA12 during cyst development in vitro after differentiation of the tachyzoite-stage parasitophorous vacuole. By day 1 postdifferentiation, GRA1, GRA4, GRA6, GRA9, and GRA12 colocalized with Dolichos biflorus agglutinin stain at the cyst periphery. In contrast, GRA2 remained in the cyst matrix. By day 2 postdifferentiation, coinciding with localization of GRA2 to the cyst periphery, GRA1, GRA4, GRA6, and GRA9 established a continuous matrix pattern in the cyst. In contrast, GRA2 and GRA12 were colocalized in prominent cyst matrix puncta throughout cyst development. While GRA2, GRA6, and GRA12 localized in outer and inner layers of the cyst wall, GRA1, GRA4, and GRA9 localized predominantly in the inner layers of the cyst wall. GRA2 and GRA12 were colocalized in the cyst wall by day 7 postdifferentiation. However, by day 10 postdifferentiation, GRA12 was relocalized from the cyst wall to puncta in the cyst matrix. Differentiation of Δgra2 parasites revealed a defect in the ability to establish a normal cyst matrix. In addition, the deletion of any intravacuolar-network-associated GRA protein, except GRA1, reduced the rate of accumulation of cyst wall proteins at the cyst periphery relative to the cyst interior. Our findings reveal dynamic patterns of GRA protein localization during cyst development and suggest that intravacuolar-network-associated GRA proteins regulate the formation and maturation of the cyst matrix and cyst wall structures. IMPORTANCE Toxoplasma gondii establishes chronic infection in humans by forming thick-walled cysts that persist in the brain. If host immunity wanes, cysts reactivate to cause severe, and often lethal, toxoplasmic encephalitis. There is no available therapy to eliminate cysts or to prevent their reactivation. Moreover, how the vital and characteristic cyst matrix and cyst wall structures develop is poorly understood. Here, we visualized and tracked the localization of Toxoplasma intravacuolar-network-associated dense granule (GRA) proteins during cyst development in vitro. Intravacuolar-network GRAs were present within the cyst matrix and at the cyst wall in developing cysts, and genetic deletion of intravacuolar-network-associated GRAs reduced the rate of accumulation of cyst wall material at the cyst periphery. Our results show that intravacuolar-network-associated GRAs, particularly GRA2 and GRA12, play dynamic and essential roles in the development and maturation of the cyst matrix and the cyst wall structures.Rebekah B. GuevaraBarbara A. FoxAlejandra FallaDavid J. BzikAmerican Society for MicrobiologyarticleToxoplasma gondiicystschronic infectioncyst wallcyst matrixintravacuolar networkMicrobiologyQR1-502ENmSphere, Vol 4, Iss 5 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Toxoplasma gondii cysts chronic infection cyst wall cyst matrix intravacuolar network Microbiology QR1-502
spellingShingle	Toxoplasma gondii cysts chronic infection cyst wall cyst matrix intravacuolar network Microbiology QR1-502 Rebekah B. Guevara Barbara A. Fox Alejandra Falla David J. Bzik <named-content content-type="genus-species">Toxoplasma gondii</named-content> Intravacuolar-Network-Associated Dense Granule Proteins Regulate Maturation of the Cyst Matrix and Cyst Wall
description	ABSTRACT Little is known regarding how the chronic Toxoplasma gondii cyst develops. Here, we investigated intravacuolar-network-associated dense granule (GRA) proteins GRA1, GRA2, GRA4, GRA6, GRA9, and GRA12 during cyst development in vitro after differentiation of the tachyzoite-stage parasitophorous vacuole. By day 1 postdifferentiation, GRA1, GRA4, GRA6, GRA9, and GRA12 colocalized with Dolichos biflorus agglutinin stain at the cyst periphery. In contrast, GRA2 remained in the cyst matrix. By day 2 postdifferentiation, coinciding with localization of GRA2 to the cyst periphery, GRA1, GRA4, GRA6, and GRA9 established a continuous matrix pattern in the cyst. In contrast, GRA2 and GRA12 were colocalized in prominent cyst matrix puncta throughout cyst development. While GRA2, GRA6, and GRA12 localized in outer and inner layers of the cyst wall, GRA1, GRA4, and GRA9 localized predominantly in the inner layers of the cyst wall. GRA2 and GRA12 were colocalized in the cyst wall by day 7 postdifferentiation. However, by day 10 postdifferentiation, GRA12 was relocalized from the cyst wall to puncta in the cyst matrix. Differentiation of Δgra2 parasites revealed a defect in the ability to establish a normal cyst matrix. In addition, the deletion of any intravacuolar-network-associated GRA protein, except GRA1, reduced the rate of accumulation of cyst wall proteins at the cyst periphery relative to the cyst interior. Our findings reveal dynamic patterns of GRA protein localization during cyst development and suggest that intravacuolar-network-associated GRA proteins regulate the formation and maturation of the cyst matrix and cyst wall structures. IMPORTANCE Toxoplasma gondii establishes chronic infection in humans by forming thick-walled cysts that persist in the brain. If host immunity wanes, cysts reactivate to cause severe, and often lethal, toxoplasmic encephalitis. There is no available therapy to eliminate cysts or to prevent their reactivation. Moreover, how the vital and characteristic cyst matrix and cyst wall structures develop is poorly understood. Here, we visualized and tracked the localization of Toxoplasma intravacuolar-network-associated dense granule (GRA) proteins during cyst development in vitro. Intravacuolar-network GRAs were present within the cyst matrix and at the cyst wall in developing cysts, and genetic deletion of intravacuolar-network-associated GRAs reduced the rate of accumulation of cyst wall material at the cyst periphery. Our results show that intravacuolar-network-associated GRAs, particularly GRA2 and GRA12, play dynamic and essential roles in the development and maturation of the cyst matrix and the cyst wall structures.
format	article
author	Rebekah B. Guevara Barbara A. Fox Alejandra Falla David J. Bzik
author_facet	Rebekah B. Guevara Barbara A. Fox Alejandra Falla David J. Bzik
author_sort	Rebekah B. Guevara
title	<named-content content-type="genus-species">Toxoplasma gondii</named-content> Intravacuolar-Network-Associated Dense Granule Proteins Regulate Maturation of the Cyst Matrix and Cyst Wall
title_short	<named-content content-type="genus-species">Toxoplasma gondii</named-content> Intravacuolar-Network-Associated Dense Granule Proteins Regulate Maturation of the Cyst Matrix and Cyst Wall
title_full	<named-content content-type="genus-species">Toxoplasma gondii</named-content> Intravacuolar-Network-Associated Dense Granule Proteins Regulate Maturation of the Cyst Matrix and Cyst Wall
title_fullStr	<named-content content-type="genus-species">Toxoplasma gondii</named-content> Intravacuolar-Network-Associated Dense Granule Proteins Regulate Maturation of the Cyst Matrix and Cyst Wall
title_full_unstemmed	<named-content content-type="genus-species">Toxoplasma gondii</named-content> Intravacuolar-Network-Associated Dense Granule Proteins Regulate Maturation of the Cyst Matrix and Cyst Wall
title_sort	<named-content content-type="genus-species">toxoplasma gondii</named-content> intravacuolar-network-associated dense granule proteins regulate maturation of the cyst matrix and cyst wall
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/0dd4b654c23e49efa692482b7cda66d3
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<named-content content-type="genus-species">Toxoplasma gondii</named-content> Intravacuolar-Network-Associated Dense Granule Proteins Regulate Maturation of the Cyst Matrix and Cyst Wall

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