Toxoplasma bradyzoites exhibit physiological plasticity of calcium and energy stores controlling motility and egress
Toxoplasma gondii has evolved different developmental stages for disseminating during acute infection (i.e., tachyzoites) and establishing chronic infection (i.e., bradyzoites). Calcium ion (Ca2+) signaling tightly regulates the lytic cycle of tachyzoites by controlling microneme secretion and motil...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/73011 |
| _version_ | 1811236739429171200 |
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| author | Yong Fu Kevin M Brown Nathaniel G Jones Silvia NJ Moreno L David Sibley |
| author_facet | Yong Fu Kevin M Brown Nathaniel G Jones Silvia NJ Moreno L David Sibley |
| author_sort | Yong Fu |
| collection | DOAJ |
| description | Toxoplasma gondii has evolved different developmental stages for disseminating during acute infection (i.e., tachyzoites) and establishing chronic infection (i.e., bradyzoites). Calcium ion (Ca2+) signaling tightly regulates the lytic cycle of tachyzoites by controlling microneme secretion and motility to drive egress and cell invasion. However, the roles of Ca2+ signaling pathways in bradyzoites remain largely unexplored. Here, we show that Ca2+ responses are highly restricted in bradyzoites and that they fail to egress in response to agonists. Development of dual-reporter parasites revealed dampened Ca2+ responses and minimal microneme secretion by bradyzoites induced in vitro or harvested from infected mice and tested ex vivo. Ratiometric Ca2+ imaging demonstrated lower Ca2+ basal levels, reduced magnitude, and slower Ca2+ kinetics in bradyzoites compared with tachyzoites stimulated with agonists. Diminished responses in bradyzoites were associated with downregulation of Ca2+-ATPases involved in intracellular Ca2+ storage in the endoplasmic reticulum (ER) and acidocalcisomes. Once liberated from cysts by trypsin digestion, bradyzoites incubated in glucose plus Ca2+ rapidly restored their intracellular Ca2+ and ATP stores, leading to enhanced gliding. Collectively, our findings indicate that intracellular bradyzoites exhibit dampened Ca2+ signaling and lower energy levels that restrict egress, and yet upon release they rapidly respond to changes in the environment to regain motility. |
| first_indexed | 2024-04-12T12:13:19Z |
| format | Article |
| id | doaj.art-36825b911eff45ed9701b6ee6fca8109 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:13:19Z |
| publishDate | 2021-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-36825b911eff45ed9701b6ee6fca81092022-12-22T03:33:30ZengeLife Sciences Publications LtdeLife2050-084X2021-12-011010.7554/eLife.73011Toxoplasma bradyzoites exhibit physiological plasticity of calcium and energy stores controlling motility and egressYong Fu0Kevin M Brown1Nathaniel G Jones2https://orcid.org/0000-0001-7328-4487Silvia NJ Moreno3https://orcid.org/0000-0002-2041-6295L David Sibley4https://orcid.org/0000-0001-7110-0285Department of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St Louis, United StatesDepartment of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St Louis, United StatesDepartment of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St Louis, United StatesCenter for Tropical and Emerging Global Diseases and Department of Cellular Biology, University of Georgia, Athens, United StatesDepartment of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St Louis, United StatesToxoplasma gondii has evolved different developmental stages for disseminating during acute infection (i.e., tachyzoites) and establishing chronic infection (i.e., bradyzoites). Calcium ion (Ca2+) signaling tightly regulates the lytic cycle of tachyzoites by controlling microneme secretion and motility to drive egress and cell invasion. However, the roles of Ca2+ signaling pathways in bradyzoites remain largely unexplored. Here, we show that Ca2+ responses are highly restricted in bradyzoites and that they fail to egress in response to agonists. Development of dual-reporter parasites revealed dampened Ca2+ responses and minimal microneme secretion by bradyzoites induced in vitro or harvested from infected mice and tested ex vivo. Ratiometric Ca2+ imaging demonstrated lower Ca2+ basal levels, reduced magnitude, and slower Ca2+ kinetics in bradyzoites compared with tachyzoites stimulated with agonists. Diminished responses in bradyzoites were associated with downregulation of Ca2+-ATPases involved in intracellular Ca2+ storage in the endoplasmic reticulum (ER) and acidocalcisomes. Once liberated from cysts by trypsin digestion, bradyzoites incubated in glucose plus Ca2+ rapidly restored their intracellular Ca2+ and ATP stores, leading to enhanced gliding. Collectively, our findings indicate that intracellular bradyzoites exhibit dampened Ca2+ signaling and lower energy levels that restrict egress, and yet upon release they rapidly respond to changes in the environment to regain motility.https://elifesciences.org/articles/73011tissue cystchronic infectioncalcium signalingexocytosisdormancyreactivation |
| spellingShingle | Yong Fu Kevin M Brown Nathaniel G Jones Silvia NJ Moreno L David Sibley Toxoplasma bradyzoites exhibit physiological plasticity of calcium and energy stores controlling motility and egress eLife tissue cyst chronic infection calcium signaling exocytosis dormancy reactivation |
| title | Toxoplasma bradyzoites exhibit physiological plasticity of calcium and energy stores controlling motility and egress |
| title_full | Toxoplasma bradyzoites exhibit physiological plasticity of calcium and energy stores controlling motility and egress |
| title_fullStr | Toxoplasma bradyzoites exhibit physiological plasticity of calcium and energy stores controlling motility and egress |
| title_full_unstemmed | Toxoplasma bradyzoites exhibit physiological plasticity of calcium and energy stores controlling motility and egress |
| title_short | Toxoplasma bradyzoites exhibit physiological plasticity of calcium and energy stores controlling motility and egress |
| title_sort | toxoplasma bradyzoites exhibit physiological plasticity of calcium and energy stores controlling motility and egress |
| topic | tissue cyst chronic infection calcium signaling exocytosis dormancy reactivation |
| url | https://elifesciences.org/articles/73011 |
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