The <italic toggle="yes">Toxoplasma gondii</italic> Active Serine Hydrolase 4 Regulates Parasite Division and Intravacuolar Parasite Architecture

ABSTRACT Hydrolase are enzymes that regulate diverse biological processes, including posttranslational protein modifications. Recent work identified four active serine hydrolases (ASHs) in Toxoplasma gondii as candidate depalmitoylases. However, only TgPPT1 (ASH1) has been confirmed to remove palmit...

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Autores principales:	Ian T. Foe, Ouma Onguka, Katherine Amberg-Johnson, Rikki M. Garner, Neri Amara, Wandy Beatty, Ellen Yeh, Matthew Bogyo
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	ASH proteins serine hydrolase cell division intravacuolar organization Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/0e40db20321c4986a54345682c61beaa
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spelling	oai:doaj.org-article:0e40db20321c4986a54345682c61beaa2021-11-15T15:22:26ZThe <italic toggle="yes">Toxoplasma gondii</italic> Active Serine Hydrolase 4 Regulates Parasite Division and Intravacuolar Parasite Architecture10.1128/mSphere.00393-182379-5042https://doaj.org/article/0e40db20321c4986a54345682c61beaa2018-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00393-18https://doaj.org/toc/2379-5042ABSTRACT Hydrolase are enzymes that regulate diverse biological processes, including posttranslational protein modifications. Recent work identified four active serine hydrolases (ASHs) in Toxoplasma gondii as candidate depalmitoylases. However, only TgPPT1 (ASH1) has been confirmed to remove palmitate from proteins. ASH4 (TgME49_264290) was reported to be refractory to genetic disruption. We demonstrate that recombinant ASH4 is an esterase that processes short acyl esters but not palmitoyl thioesters. Genetic disruption of ASH4 causes defects in cell division and premature scission of parasites from residual bodies. These defects lead to the presence of vacuoles with a disordered intravacuolar architecture, with parasites arranged in pairs around multiple residual bodies. Importantly, we found that the deletion of ASH4 correlates with a defect in radial dispersion from host cells after egress. This defect in dispersion of parasites is a general phenomenon that is observed for disordered vacuoles that occur at low frequency in wild-type parasites, suggesting a possible general link between intravacuolar organization and dispersion after egress. IMPORTANCE This work defines the function of an enzyme in the obligate intracellular parasite Toxoplasma gondii. We show that this previously uncharacterized enzyme is critical for aspects of cellular division by the parasite and that loss of this enzyme leads to parasites with cell division defects and which also are disorganized inside their vacuoles. This leads to defects in the ability of the parasite to disseminate from the site of an infection and may have a significant impact on the parasite's overall infectivity of a host organism.Ian T. FoeOuma OngukaKatherine Amberg-JohnsonRikki M. GarnerNeri AmaraWandy BeattyEllen YehMatthew BogyoAmerican Society for MicrobiologyarticleASH proteinsserine hydrolasecell divisionintravacuolar organizationMicrobiologyQR1-502ENmSphere, Vol 3, Iss 5 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	ASH proteins serine hydrolase cell division intravacuolar organization Microbiology QR1-502
spellingShingle	ASH proteins serine hydrolase cell division intravacuolar organization Microbiology QR1-502 Ian T. Foe Ouma Onguka Katherine Amberg-Johnson Rikki M. Garner Neri Amara Wandy Beatty Ellen Yeh Matthew Bogyo The <italic toggle="yes">Toxoplasma gondii</italic> Active Serine Hydrolase 4 Regulates Parasite Division and Intravacuolar Parasite Architecture
description	ABSTRACT Hydrolase are enzymes that regulate diverse biological processes, including posttranslational protein modifications. Recent work identified four active serine hydrolases (ASHs) in Toxoplasma gondii as candidate depalmitoylases. However, only TgPPT1 (ASH1) has been confirmed to remove palmitate from proteins. ASH4 (TgME49_264290) was reported to be refractory to genetic disruption. We demonstrate that recombinant ASH4 is an esterase that processes short acyl esters but not palmitoyl thioesters. Genetic disruption of ASH4 causes defects in cell division and premature scission of parasites from residual bodies. These defects lead to the presence of vacuoles with a disordered intravacuolar architecture, with parasites arranged in pairs around multiple residual bodies. Importantly, we found that the deletion of ASH4 correlates with a defect in radial dispersion from host cells after egress. This defect in dispersion of parasites is a general phenomenon that is observed for disordered vacuoles that occur at low frequency in wild-type parasites, suggesting a possible general link between intravacuolar organization and dispersion after egress. IMPORTANCE This work defines the function of an enzyme in the obligate intracellular parasite Toxoplasma gondii. We show that this previously uncharacterized enzyme is critical for aspects of cellular division by the parasite and that loss of this enzyme leads to parasites with cell division defects and which also are disorganized inside their vacuoles. This leads to defects in the ability of the parasite to disseminate from the site of an infection and may have a significant impact on the parasite's overall infectivity of a host organism.
format	article
author	Ian T. Foe Ouma Onguka Katherine Amberg-Johnson Rikki M. Garner Neri Amara Wandy Beatty Ellen Yeh Matthew Bogyo
author_facet	Ian T. Foe Ouma Onguka Katherine Amberg-Johnson Rikki M. Garner Neri Amara Wandy Beatty Ellen Yeh Matthew Bogyo
author_sort	Ian T. Foe
title	The <italic toggle="yes">Toxoplasma gondii</italic> Active Serine Hydrolase 4 Regulates Parasite Division and Intravacuolar Parasite Architecture
title_short	The <italic toggle="yes">Toxoplasma gondii</italic> Active Serine Hydrolase 4 Regulates Parasite Division and Intravacuolar Parasite Architecture
title_full	The <italic toggle="yes">Toxoplasma gondii</italic> Active Serine Hydrolase 4 Regulates Parasite Division and Intravacuolar Parasite Architecture
title_fullStr	The <italic toggle="yes">Toxoplasma gondii</italic> Active Serine Hydrolase 4 Regulates Parasite Division and Intravacuolar Parasite Architecture
title_full_unstemmed	The <italic toggle="yes">Toxoplasma gondii</italic> Active Serine Hydrolase 4 Regulates Parasite Division and Intravacuolar Parasite Architecture
title_sort	<italic toggle="yes">toxoplasma gondii</italic> active serine hydrolase 4 regulates parasite division and intravacuolar parasite architecture
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/0e40db20321c4986a54345682c61beaa
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The <italic toggle="yes">Toxoplasma gondii</italic> Active Serine Hydrolase 4 Regulates Parasite Division and Intravacuolar Parasite Architecture

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