Phosphorylation of <italic toggle="yes">Toxoplasma gondii</italic> Secreted Proteins during Acute and Chronic Stages of Infection

ABSTRACT The intracellular parasite Toxoplasma gondii resides within a membrane-bound parasitophorous vacuole (PV) and secretes an array of proteins to establish this replicative niche. It has been shown previously that Toxoplasma secretes kinases and that numerous proteins are phosphorylated after...

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Autores principales:	Joanna C. Young, Malgorzata Broncel, Helena Teague, Matt R. G. Russell, Olivia L. McGovern, Matt Renshaw, David Frith, Ambrosius P. Snijders, Lucy Collinson, Vern B. Carruthers, Sarah E. Ewald, Moritz Treeck
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Publicado:	American Society for Microbiology 2020
Materias:	host-pathogen interaction virulence factors chronic infection protein phosphorylation Microbiology QR1-502
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spelling	oai:doaj.org-article:8ec188a235d64c0fb4aaa3600be59d6f2021-11-15T15:30:59ZPhosphorylation of <italic toggle="yes">Toxoplasma gondii</italic> Secreted Proteins during Acute and Chronic Stages of Infection10.1128/mSphere.00792-202379-5042https://doaj.org/article/8ec188a235d64c0fb4aaa3600be59d6f2020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00792-20https://doaj.org/toc/2379-5042ABSTRACT The intracellular parasite Toxoplasma gondii resides within a membrane-bound parasitophorous vacuole (PV) and secretes an array of proteins to establish this replicative niche. It has been shown previously that Toxoplasma secretes kinases and that numerous proteins are phosphorylated after secretion. Here, we assess the role of the phosphorylation of strand-forming protein 1 (SFP1) and the related protein GRA29, two secreted proteins with unknown function. We show that both proteins form stranded structures in the PV that are independent of the previously described intravacuolar network or actin. SFP1 and GRA29 can each form these structures independently of other Toxoplasma secreted proteins, although GRA29 appears to regulate SFP1 strands. We show that an unstructured region at the C termini of SFP1 and GRA29 is required for the formation of strands and that mimicking the phosphorylation of this domain of SFP1 negatively regulates strand development. When tachyzoites convert to chronic-stage bradyzoites, both proteins show a dispersed localization throughout the cyst matrix. Many secreted proteins are reported to dynamically redistribute as the cyst forms, and secreted kinases are known to play a role in cyst formation. Using quantitative phosphoproteome and proteome analyses comparing tachyzoite and early bradyzoite stages, we reveal widespread differential phosphorylation of secreted proteins. While we found no direct evidence for phosphorylation playing a dominant role for SFP1/GRA29 redistribution in the cyst, these data support a model in which secreted kinases and phosphatases contribute to the regulation of secreted proteins during stage conversion. IMPORTANCE Toxoplasma gondii is a common parasite that infects up to one-third of the human population. Initially, the parasite grows rapidly, infecting and destroying cells of the host, but subsequently switches to a slow-growing form and establishes chronic infection. In both stages, the parasite lives within a membrane-bound vacuole within the host cell, but in the chronic stage, a durable cyst wall is synthesized, which provides protection to the parasite during transmission to a new host. Toxoplasma secretes proteins into the vacuole to build its replicative niche, and previous studies identified many of these proteins as phosphorylated. We investigate two secreted proteins and show that a phosphorylated region plays an important role in their regulation in acute stages. We also observed widespread phosphorylation of secreted proteins when parasites convert from acute to chronic stages, providing new insight into how the cyst wall may be dynamically regulated.Joanna C. YoungMalgorzata BroncelHelena TeagueMatt R. G. RussellOlivia L. McGovernMatt RenshawDavid FrithAmbrosius P. SnijdersLucy CollinsonVern B. CarruthersSarah E. EwaldMoritz TreeckAmerican Society for Microbiologyarticlehost-pathogen interactionvirulence factorschronic infectionprotein phosphorylationMicrobiologyQR1-502ENmSphere, Vol 5, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	host-pathogen interaction virulence factors chronic infection protein phosphorylation Microbiology QR1-502
spellingShingle	host-pathogen interaction virulence factors chronic infection protein phosphorylation Microbiology QR1-502 Joanna C. Young Malgorzata Broncel Helena Teague Matt R. G. Russell Olivia L. McGovern Matt Renshaw David Frith Ambrosius P. Snijders Lucy Collinson Vern B. Carruthers Sarah E. Ewald Moritz Treeck Phosphorylation of <italic toggle="yes">Toxoplasma gondii</italic> Secreted Proteins during Acute and Chronic Stages of Infection
description	ABSTRACT The intracellular parasite Toxoplasma gondii resides within a membrane-bound parasitophorous vacuole (PV) and secretes an array of proteins to establish this replicative niche. It has been shown previously that Toxoplasma secretes kinases and that numerous proteins are phosphorylated after secretion. Here, we assess the role of the phosphorylation of strand-forming protein 1 (SFP1) and the related protein GRA29, two secreted proteins with unknown function. We show that both proteins form stranded structures in the PV that are independent of the previously described intravacuolar network or actin. SFP1 and GRA29 can each form these structures independently of other Toxoplasma secreted proteins, although GRA29 appears to regulate SFP1 strands. We show that an unstructured region at the C termini of SFP1 and GRA29 is required for the formation of strands and that mimicking the phosphorylation of this domain of SFP1 negatively regulates strand development. When tachyzoites convert to chronic-stage bradyzoites, both proteins show a dispersed localization throughout the cyst matrix. Many secreted proteins are reported to dynamically redistribute as the cyst forms, and secreted kinases are known to play a role in cyst formation. Using quantitative phosphoproteome and proteome analyses comparing tachyzoite and early bradyzoite stages, we reveal widespread differential phosphorylation of secreted proteins. While we found no direct evidence for phosphorylation playing a dominant role for SFP1/GRA29 redistribution in the cyst, these data support a model in which secreted kinases and phosphatases contribute to the regulation of secreted proteins during stage conversion. IMPORTANCE Toxoplasma gondii is a common parasite that infects up to one-third of the human population. Initially, the parasite grows rapidly, infecting and destroying cells of the host, but subsequently switches to a slow-growing form and establishes chronic infection. In both stages, the parasite lives within a membrane-bound vacuole within the host cell, but in the chronic stage, a durable cyst wall is synthesized, which provides protection to the parasite during transmission to a new host. Toxoplasma secretes proteins into the vacuole to build its replicative niche, and previous studies identified many of these proteins as phosphorylated. We investigate two secreted proteins and show that a phosphorylated region plays an important role in their regulation in acute stages. We also observed widespread phosphorylation of secreted proteins when parasites convert from acute to chronic stages, providing new insight into how the cyst wall may be dynamically regulated.
format	article
author	Joanna C. Young Malgorzata Broncel Helena Teague Matt R. G. Russell Olivia L. McGovern Matt Renshaw David Frith Ambrosius P. Snijders Lucy Collinson Vern B. Carruthers Sarah E. Ewald Moritz Treeck
author_facet	Joanna C. Young Malgorzata Broncel Helena Teague Matt R. G. Russell Olivia L. McGovern Matt Renshaw David Frith Ambrosius P. Snijders Lucy Collinson Vern B. Carruthers Sarah E. Ewald Moritz Treeck
author_sort	Joanna C. Young
title	Phosphorylation of <italic toggle="yes">Toxoplasma gondii</italic> Secreted Proteins during Acute and Chronic Stages of Infection
title_short	Phosphorylation of <italic toggle="yes">Toxoplasma gondii</italic> Secreted Proteins during Acute and Chronic Stages of Infection
title_full	Phosphorylation of <italic toggle="yes">Toxoplasma gondii</italic> Secreted Proteins during Acute and Chronic Stages of Infection
title_fullStr	Phosphorylation of <italic toggle="yes">Toxoplasma gondii</italic> Secreted Proteins during Acute and Chronic Stages of Infection
title_full_unstemmed	Phosphorylation of <italic toggle="yes">Toxoplasma gondii</italic> Secreted Proteins during Acute and Chronic Stages of Infection
title_sort	phosphorylation of <italic toggle="yes">toxoplasma gondii</italic> secreted proteins during acute and chronic stages of infection
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/8ec188a235d64c0fb4aaa3600be59d6f
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Phosphorylation of <italic toggle="yes">Toxoplasma gondii</italic> Secreted Proteins during Acute and Chronic Stages of Infection

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