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Toxoplasma gondii Ingests and Digests Host Cytosolic Proteins
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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Microbiology
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161261/ https://www.ncbi.nlm.nih.gov/pubmed/25028423 http://dx.doi.org/10.1128/mBio.01188-14 |
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author | Dou, Zhicheng McGovern, Olivia L. Di Cristina, Manlio Carruthers, Vern B. |
author_facet | Dou, Zhicheng McGovern, Olivia L. Di Cristina, Manlio Carruthers, Vern B. |
author_sort | Dou, Zhicheng |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4161261 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | American Society of Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-41612612014-09-11 Toxoplasma gondii Ingests and Digests Host Cytosolic Proteins Dou, Zhicheng McGovern, Olivia L. Di Cristina, Manlio Carruthers, Vern B. mBio Research Article 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. American Society of Microbiology 2014-07-15 /pmc/articles/PMC4161261/ /pubmed/25028423 http://dx.doi.org/10.1128/mBio.01188-14 Text en Copyright © 2014 Dou et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Dou, Zhicheng McGovern, Olivia L. Di Cristina, Manlio Carruthers, Vern B. Toxoplasma gondii Ingests and Digests Host Cytosolic Proteins |
title | Toxoplasma gondii Ingests and Digests Host Cytosolic Proteins |
title_full | Toxoplasma gondii Ingests and Digests Host Cytosolic Proteins |
title_fullStr | Toxoplasma gondii Ingests and Digests Host Cytosolic Proteins |
title_full_unstemmed | Toxoplasma gondii Ingests and Digests Host Cytosolic Proteins |
title_short | Toxoplasma gondii Ingests and Digests Host Cytosolic Proteins |
title_sort | toxoplasma gondii ingests and digests host cytosolic proteins |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161261/ https://www.ncbi.nlm.nih.gov/pubmed/25028423 http://dx.doi.org/10.1128/mBio.01188-14 |
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