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mSphere. 2018 Sep 19;3(5). pii: e00393-18. doi: 10.1128/mSphere.00393-18.

The Toxoplasma gondii Active Serine Hydrolase 4 Regulates Parasite Division and Intravacuolar Parasite Architecture.

Author information

1
Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
2
Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA.
3
Biophysics Program, Stanford University School of Medicine, Stanford, California, USA.
4
Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, Missouri, USA.
5
Department of Biochemistry, Stanford University School of Medicine, Stanford, California, USA.
6
Chan Zuckerburg Biohub, San Francisco, California, USA.
7
Department of Pathology, Stanford University School of Medicine, Stanford, California, USA mbogyo@stanford.edu.

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.

KEYWORDS:

ASH proteins; cell division; intravacuolar organization; serine hydrolase

PMID:
30232166
PMCID:
PMC6147133
DOI:
10.1128/mSphere.00393-18
[Indexed for MEDLINE]
Free PMC Article

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