The enteric pathogen Cryptosporidium parvum exports proteins into the cytosol of the infected host cell
The parasite Cryptosporidium is responsible for diarrheal disease in young children causing death, malnutrition, and growth delay. Cryptosporidium invades enterocytes where it develops in a unique intracellular niche. Infected cells exhibit profound changes in morphology, physiology, and transcripti...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2021-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/70451 |
| _version_ | 1818019204547215360 |
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| author | Jennifer E Dumaine Adam Sateriale Alexis R Gibson Amita G Reddy Jodi A Gullicksrud Emma N Hunter Joseph T Clark Boris Striepen |
| author_facet | Jennifer E Dumaine Adam Sateriale Alexis R Gibson Amita G Reddy Jodi A Gullicksrud Emma N Hunter Joseph T Clark Boris Striepen |
| author_sort | Jennifer E Dumaine |
| collection | DOAJ |
| description | The parasite Cryptosporidium is responsible for diarrheal disease in young children causing death, malnutrition, and growth delay. Cryptosporidium invades enterocytes where it develops in a unique intracellular niche. Infected cells exhibit profound changes in morphology, physiology, and transcriptional activity. How the parasite effects these changes is poorly understood. We explored the localization of highly polymorphic proteins and found members of the Cryptosporidium parvum MEDLE protein family to be translocated into the cytosol of infected cells. All intracellular life stages engage in this export, which occurs after completion of invasion. Mutational studies defined an N-terminal host-targeting motif and demonstrated proteolytic processing at a specific leucine residue. Direct expression of MEDLE2 in mammalian cells triggered an ER stress response, which was also observed during infection. Taken together, our studies reveal the presence of a Cryptosporidium secretion system capable of delivering parasite proteins into the infected enterocyte. |
| first_indexed | 2024-04-14T07:48:11Z |
| format | Article |
| id | doaj.art-ae430fdaa3064faba2888e2acc41c05f |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:48:11Z |
| publishDate | 2021-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-ae430fdaa3064faba2888e2acc41c05f2022-12-22T02:05:16ZengeLife Sciences Publications LtdeLife2050-084X2021-12-011010.7554/eLife.70451The enteric pathogen Cryptosporidium parvum exports proteins into the cytosol of the infected host cellJennifer E Dumaine0https://orcid.org/0000-0002-5975-4523Adam Sateriale1Alexis R Gibson2https://orcid.org/0000-0003-1078-4841Amita G Reddy3Jodi A Gullicksrud4Emma N Hunter5Joseph T Clark6Boris Striepen7https://orcid.org/0000-0002-7426-432XDepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, United StatesDepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, United StatesDepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, United StatesFranklin College of Arts and Science, University of Georgia, Athens, United StatesDepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, United StatesDepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, United StatesDepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, United StatesDepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, United StatesThe parasite Cryptosporidium is responsible for diarrheal disease in young children causing death, malnutrition, and growth delay. Cryptosporidium invades enterocytes where it develops in a unique intracellular niche. Infected cells exhibit profound changes in morphology, physiology, and transcriptional activity. How the parasite effects these changes is poorly understood. We explored the localization of highly polymorphic proteins and found members of the Cryptosporidium parvum MEDLE protein family to be translocated into the cytosol of infected cells. All intracellular life stages engage in this export, which occurs after completion of invasion. Mutational studies defined an N-terminal host-targeting motif and demonstrated proteolytic processing at a specific leucine residue. Direct expression of MEDLE2 in mammalian cells triggered an ER stress response, which was also observed during infection. Taken together, our studies reveal the presence of a Cryptosporidium secretion system capable of delivering parasite proteins into the infected enterocyte.https://elifesciences.org/articles/70451Cryptosporidiumprotein exporteffectorhost-pathogen interactions |
| spellingShingle | Jennifer E Dumaine Adam Sateriale Alexis R Gibson Amita G Reddy Jodi A Gullicksrud Emma N Hunter Joseph T Clark Boris Striepen The enteric pathogen Cryptosporidium parvum exports proteins into the cytosol of the infected host cell eLife Cryptosporidium protein export effector host-pathogen interactions |
| title | The enteric pathogen Cryptosporidium parvum exports proteins into the cytosol of the infected host cell |
| title_full | The enteric pathogen Cryptosporidium parvum exports proteins into the cytosol of the infected host cell |
| title_fullStr | The enteric pathogen Cryptosporidium parvum exports proteins into the cytosol of the infected host cell |
| title_full_unstemmed | The enteric pathogen Cryptosporidium parvum exports proteins into the cytosol of the infected host cell |
| title_short | The enteric pathogen Cryptosporidium parvum exports proteins into the cytosol of the infected host cell |
| title_sort | enteric pathogen cryptosporidium parvum exports proteins into the cytosol of the infected host cell |
| topic | Cryptosporidium protein export effector host-pathogen interactions |
| url | https://elifesciences.org/articles/70451 |
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