<named-content content-type="genus-species">Toxoplasma gondii</named-content> Cyclic AMP-Dependent Protein Kinase Subunit 3 Is Involved in the Switch from Tachyzoite to Bradyzoite Development

ABSTRACT Toxoplasma gondii is an obligate intracellular apicomplexan parasite that infects warm-blooded vertebrates, including humans. Asexual reproduction in T. gondii allows it to switch between the rapidly replicating tachyzoite and quiescent bradyzoite life cycle stages. A transient cyclic AMP (...

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Autores principales:	Tatsuki Sugi, Yan Fen Ma, Tadakimi Tomita, Fumi Murakoshi, Michael S. Eaton, Rama Yakubu, Bing Han, Vincent Tu, Kentaro Kato, Shin-Ichiro Kawazu, Nishith Gupta, Elena S. Suvorova, Michael W. White, Kami Kim, Louis M. Weiss
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/7a6068404b7649e8a47449c1def855c2
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spelling	oai:doaj.org-article:7a6068404b7649e8a47449c1def855c22021-11-15T15:50:17Z<named-content content-type="genus-species">Toxoplasma gondii</named-content> Cyclic AMP-Dependent Protein Kinase Subunit 3 Is Involved in the Switch from Tachyzoite to Bradyzoite Development10.1128/mBio.00755-162150-7511https://doaj.org/article/7a6068404b7649e8a47449c1def855c22016-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00755-16https://doaj.org/toc/2150-7511ABSTRACT Toxoplasma gondii is an obligate intracellular apicomplexan parasite that infects warm-blooded vertebrates, including humans. Asexual reproduction in T. gondii allows it to switch between the rapidly replicating tachyzoite and quiescent bradyzoite life cycle stages. A transient cyclic AMP (cAMP) pulse promotes bradyzoite differentiation, whereas a prolonged elevation of cAMP inhibits this process. We investigated the mechanism(s) by which differential modulation of cAMP exerts a bidirectional effect on parasite differentiation. There are three protein kinase A (PKA) catalytic subunits (TgPKAc1 to -3) expressed in T. gondii. Unlike TgPKAc1 and TgPKAc2, which are conserved in the phylum Apicomplexa, TgPKAc3 appears evolutionarily divergent and specific to coccidian parasites. TgPKAc1 and TgPKAc2 are distributed in the cytomembranes, whereas TgPKAc3 resides in the cytosol. TgPKAc3 was genetically ablated in a type II cyst-forming strain of T. gondii (PruΔku80Δhxgprt) and in a type I strain (RHΔku80Δhxgprt), which typically does not form cysts. The Δpkac3 mutant exhibited slower growth than the parental and complemented strains, which correlated with a higher basal rate of tachyzoite-to-bradyzoite differentiation. 3-Isobutyl-1-methylxanthine (IBMX) treatment, which elevates cAMP levels, maintained wild-type parasites as tachyzoites under bradyzoite induction culture conditions (pH 8.2/low CO2), whereas the Δpkac3 mutant failed to respond to the treatment. This suggests that TgPKAc3 is the factor responsible for the cAMP-dependent tachyzoite maintenance. In addition, the Δpkac3 mutant had a defect in the production of brain cysts in vivo, suggesting that a substrate of TgPKAc3 is probably involved in the persistence of this parasite in the intermediate host animals. IMPORTANCE Toxoplasma gondii is one of the most prevalent eukaryotic parasites in mammals, including humans. Parasites can switch from rapidly replicating tachyzoites responsible for acute infection to slowly replicating bradyzoites that persist as a latent infection. Previous studies have demonstrated that T. gondii cAMP signaling can induce or suppress bradyzoite differentiation, depending on the strength and duration of cAMP signal. Here, we report that TgPKAc3 is responsible for cAMP-dependent tachyzoite maintenance while suppressing differentiation into bradyzoites, revealing one mechanism underlying how this parasite transduces cAMP signals during differentiation.Tatsuki SugiYan Fen MaTadakimi TomitaFumi MurakoshiMichael S. EatonRama YakubuBing HanVincent TuKentaro KatoShin-Ichiro KawazuNishith GuptaElena S. SuvorovaMichael W. WhiteKami KimLouis M. WeissAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 3 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Tatsuki Sugi Yan Fen Ma Tadakimi Tomita Fumi Murakoshi Michael S. Eaton Rama Yakubu Bing Han Vincent Tu Kentaro Kato Shin-Ichiro Kawazu Nishith Gupta Elena S. Suvorova Michael W. White Kami Kim Louis M. Weiss <named-content content-type="genus-species">Toxoplasma gondii</named-content> Cyclic AMP-Dependent Protein Kinase Subunit 3 Is Involved in the Switch from Tachyzoite to Bradyzoite Development
description	ABSTRACT Toxoplasma gondii is an obligate intracellular apicomplexan parasite that infects warm-blooded vertebrates, including humans. Asexual reproduction in T. gondii allows it to switch between the rapidly replicating tachyzoite and quiescent bradyzoite life cycle stages. A transient cyclic AMP (cAMP) pulse promotes bradyzoite differentiation, whereas a prolonged elevation of cAMP inhibits this process. We investigated the mechanism(s) by which differential modulation of cAMP exerts a bidirectional effect on parasite differentiation. There are three protein kinase A (PKA) catalytic subunits (TgPKAc1 to -3) expressed in T. gondii. Unlike TgPKAc1 and TgPKAc2, which are conserved in the phylum Apicomplexa, TgPKAc3 appears evolutionarily divergent and specific to coccidian parasites. TgPKAc1 and TgPKAc2 are distributed in the cytomembranes, whereas TgPKAc3 resides in the cytosol. TgPKAc3 was genetically ablated in a type II cyst-forming strain of T. gondii (PruΔku80Δhxgprt) and in a type I strain (RHΔku80Δhxgprt), which typically does not form cysts. The Δpkac3 mutant exhibited slower growth than the parental and complemented strains, which correlated with a higher basal rate of tachyzoite-to-bradyzoite differentiation. 3-Isobutyl-1-methylxanthine (IBMX) treatment, which elevates cAMP levels, maintained wild-type parasites as tachyzoites under bradyzoite induction culture conditions (pH 8.2/low CO2), whereas the Δpkac3 mutant failed to respond to the treatment. This suggests that TgPKAc3 is the factor responsible for the cAMP-dependent tachyzoite maintenance. In addition, the Δpkac3 mutant had a defect in the production of brain cysts in vivo, suggesting that a substrate of TgPKAc3 is probably involved in the persistence of this parasite in the intermediate host animals. IMPORTANCE Toxoplasma gondii is one of the most prevalent eukaryotic parasites in mammals, including humans. Parasites can switch from rapidly replicating tachyzoites responsible for acute infection to slowly replicating bradyzoites that persist as a latent infection. Previous studies have demonstrated that T. gondii cAMP signaling can induce or suppress bradyzoite differentiation, depending on the strength and duration of cAMP signal. Here, we report that TgPKAc3 is responsible for cAMP-dependent tachyzoite maintenance while suppressing differentiation into bradyzoites, revealing one mechanism underlying how this parasite transduces cAMP signals during differentiation.
format	article
author	Tatsuki Sugi Yan Fen Ma Tadakimi Tomita Fumi Murakoshi Michael S. Eaton Rama Yakubu Bing Han Vincent Tu Kentaro Kato Shin-Ichiro Kawazu Nishith Gupta Elena S. Suvorova Michael W. White Kami Kim Louis M. Weiss
author_facet	Tatsuki Sugi Yan Fen Ma Tadakimi Tomita Fumi Murakoshi Michael S. Eaton Rama Yakubu Bing Han Vincent Tu Kentaro Kato Shin-Ichiro Kawazu Nishith Gupta Elena S. Suvorova Michael W. White Kami Kim Louis M. Weiss
author_sort	Tatsuki Sugi
title	<named-content content-type="genus-species">Toxoplasma gondii</named-content> Cyclic AMP-Dependent Protein Kinase Subunit 3 Is Involved in the Switch from Tachyzoite to Bradyzoite Development
title_short	<named-content content-type="genus-species">Toxoplasma gondii</named-content> Cyclic AMP-Dependent Protein Kinase Subunit 3 Is Involved in the Switch from Tachyzoite to Bradyzoite Development
title_full	<named-content content-type="genus-species">Toxoplasma gondii</named-content> Cyclic AMP-Dependent Protein Kinase Subunit 3 Is Involved in the Switch from Tachyzoite to Bradyzoite Development
title_fullStr	<named-content content-type="genus-species">Toxoplasma gondii</named-content> Cyclic AMP-Dependent Protein Kinase Subunit 3 Is Involved in the Switch from Tachyzoite to Bradyzoite Development
title_full_unstemmed	<named-content content-type="genus-species">Toxoplasma gondii</named-content> Cyclic AMP-Dependent Protein Kinase Subunit 3 Is Involved in the Switch from Tachyzoite to Bradyzoite Development
title_sort	<named-content content-type="genus-species">toxoplasma gondii</named-content> cyclic amp-dependent protein kinase subunit 3 is involved in the switch from tachyzoite to bradyzoite development
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/7a6068404b7649e8a47449c1def855c2
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<named-content content-type="genus-species">Toxoplasma gondii</named-content> Cyclic AMP-Dependent Protein Kinase Subunit 3 Is Involved in the Switch from Tachyzoite to Bradyzoite Development

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