<named-content content-type="genus-species">Toxoplasma gondii</named-content> Ingests and Digests Host Cytosolic Proteins

ABSTRACT The protozoan parasite Toxoplasma gondii resides within a nonfusogenic vacuole during intracellular replication. Although the limiting membrane of this vacuole provides a protective barrier to acidification and degradation by lysosomal hydrolases, it also physically segregates the parasite...

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Autores principales:	Zhicheng Dou, Olivia L. McGovern, Manlio Di Cristina, Vern B. Carruthers
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2014
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/bcd756be7db84aaf9d882e0111fdf9f7
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spelling	oai:doaj.org-article:bcd756be7db84aaf9d882e0111fdf9f72021-11-15T15:47:21Z<named-content content-type="genus-species">Toxoplasma gondii</named-content> Ingests and Digests Host Cytosolic Proteins10.1128/mBio.01188-142150-7511https://doaj.org/article/bcd756be7db84aaf9d882e0111fdf9f72014-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01188-14https://doaj.org/toc/2150-7511ABSTRACT The protozoan parasite Toxoplasma gondii resides within a nonfusogenic vacuole during intracellular replication. Although the limiting membrane of this vacuole provides a protective barrier to acidification and degradation by lysosomal hydrolases, it also physically segregates the parasite from the host cytosol. Accordingly, it has been suggested that T. gondii acquires material from the host via membrane channels or transporters. The ability of the parasite to internalize macromolecules via endocytosis during intracellular replication has not been tested. Here, we show that Toxoplasma ingests host cytosolic proteins and digests them using cathepsin L and other proteases within its endolysosomal system. Ingestion was reduced in mutant parasites lacking an intravacuolar network of tubular membranes, implicating this apparatus as a possible conduit for trafficking to the parasite. Genetic ablation of proteins involved in the pathway is associated with diminished parasite replication and virulence attenuation. We show that both virulent type I and avirulent type II strain parasites ingest and digest host-derived protein, indicating that the pathway is not restricted to highly virulent strains. The findings provide the first definitive evidence that T. gondii internalizes proteins from the host during intracellular residence and suggest that protein digestion within the endolysosomal system of the parasite contributes to toxoplasmosis. IMPORTANCE Toxoplasma gondii causes significant disease in individuals with weak immune systems. Treatment options for this infection have drawbacks, creating a need to understand how this parasite survives within the cells it infects as a prelude to interrupting its survival strategies. This study reveals that T. gondii internalizes proteins from the cytoplasm of the cells it infects and degrades such proteins within a digestive compartment within the parasite. Disruption of proteins involved in the pathway reduced parasite replication and lessened disease severity. The identification of a novel parasite ingestion pathway opens opportunities to interfere with this process and improve the outcome of infection.Zhicheng DouOlivia L. McGovernManlio Di CristinaVern B. CarruthersAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 4 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Zhicheng Dou Olivia L. McGovern Manlio Di Cristina Vern B. Carruthers <named-content content-type="genus-species">Toxoplasma gondii</named-content> Ingests and Digests Host Cytosolic Proteins
description	ABSTRACT The protozoan parasite Toxoplasma gondii resides within a nonfusogenic vacuole during intracellular replication. Although the limiting membrane of this vacuole provides a protective barrier to acidification and degradation by lysosomal hydrolases, it also physically segregates the parasite from the host cytosol. Accordingly, it has been suggested that T. gondii acquires material from the host via membrane channels or transporters. The ability of the parasite to internalize macromolecules via endocytosis during intracellular replication has not been tested. Here, we show that Toxoplasma ingests host cytosolic proteins and digests them using cathepsin L and other proteases within its endolysosomal system. Ingestion was reduced in mutant parasites lacking an intravacuolar network of tubular membranes, implicating this apparatus as a possible conduit for trafficking to the parasite. Genetic ablation of proteins involved in the pathway is associated with diminished parasite replication and virulence attenuation. We show that both virulent type I and avirulent type II strain parasites ingest and digest host-derived protein, indicating that the pathway is not restricted to highly virulent strains. The findings provide the first definitive evidence that T. gondii internalizes proteins from the host during intracellular residence and suggest that protein digestion within the endolysosomal system of the parasite contributes to toxoplasmosis. IMPORTANCE Toxoplasma gondii causes significant disease in individuals with weak immune systems. Treatment options for this infection have drawbacks, creating a need to understand how this parasite survives within the cells it infects as a prelude to interrupting its survival strategies. This study reveals that T. gondii internalizes proteins from the cytoplasm of the cells it infects and degrades such proteins within a digestive compartment within the parasite. Disruption of proteins involved in the pathway reduced parasite replication and lessened disease severity. The identification of a novel parasite ingestion pathway opens opportunities to interfere with this process and improve the outcome of infection.
format	article
author	Zhicheng Dou Olivia L. McGovern Manlio Di Cristina Vern B. Carruthers
author_facet	Zhicheng Dou Olivia L. McGovern Manlio Di Cristina Vern B. Carruthers
author_sort	Zhicheng Dou
title	<named-content content-type="genus-species">Toxoplasma gondii</named-content> Ingests and Digests Host Cytosolic Proteins
title_short	<named-content content-type="genus-species">Toxoplasma gondii</named-content> Ingests and Digests Host Cytosolic Proteins
title_full	<named-content content-type="genus-species">Toxoplasma gondii</named-content> Ingests and Digests Host Cytosolic Proteins
title_fullStr	<named-content content-type="genus-species">Toxoplasma gondii</named-content> Ingests and Digests Host Cytosolic Proteins
title_full_unstemmed	<named-content content-type="genus-species">Toxoplasma gondii</named-content> Ingests and Digests Host Cytosolic Proteins
title_sort	<named-content content-type="genus-species">toxoplasma gondii</named-content> ingests and digests host cytosolic proteins
publisher	American Society for Microbiology
publishDate	2014
url	https://doaj.org/article/bcd756be7db84aaf9d882e0111fdf9f7
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<named-content content-type="genus-species">Toxoplasma gondii</named-content> Ingests and Digests Host Cytosolic Proteins

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