{"doi":"10.7554/elife.73011","title":"Toxoplasma bradyzoites exhibit physiological plasticity of calcium and energy stores controlling motility and egress","abstract":"Toxoplasma gondii has evolved different developmental stages for disseminating during acute infection (i.e., tachyzoites) and establishing chronic infection (i.e., bradyzoites). Calcium ion (Ca 2+ ) signaling tightly regulates the lytic cycle of tachyzoites by controlling microneme secretion and motility to drive egress and cell invasion. However, the roles of Ca 2+ signaling pathways in bradyzoites remain largely unexplored. Here, we show that Ca 2+ responses are highly restricted in bradyzoites and that they fail to egress in response to agonists. Development of dual-reporter parasites revealed dampened Ca 2+ responses and minimal microneme secretion by bradyzoites induced in vitro or harvested from infected mice and tested ex vivo. Ratiometric Ca 2+ imaging demonstrated lower Ca 2+ basal levels, reduced magnitude, and slower Ca 2+ kinetics in bradyzoites compared with tachyzoites stimulated with agonists. Diminished responses in bradyzoites were associated with downregulation of Ca 2+ -ATPases involved in intracellular Ca 2+ storage in the endoplasmic reticulum (ER) and acidocalcisomes. Once liberated from cysts by trypsin digestion, bradyzoites incubated in glucose plus Ca 2+ rapidly restored their intracellular Ca 2+ and ATP stores, leading to enhanced gliding. Collectively, our findings indicate that intracellular bradyzoites exhibit dampened Ca 2+ signaling and lower energy levels that restrict egress, and yet upon release they rapidly respond to changes in the environment to regain motility.","journal":"eLife","year":2021,"id":170449,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":28,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9527,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":704104,"name":"Kevin M Brown","orcid":null,"position":1,"is_corresponding":false},{"id":703255,"name":"Nathaniel G Jones","orcid":"0000-0001-7328-4487","position":2,"is_corresponding":false},{"id":480891,"name":"Silvia N.J. Moreno","orcid":"0000-0002-2041-6295","position":3,"is_corresponding":false},{"id":317860,"name":"L. David Sibley","orcid":"0000-0001-7110-0285","position":4,"is_corresponding":false},{"id":469327,"name":"Yong Fu","orcid":"0000-0001-6480-1147","position":0,"is_corresponding":true}],"reference_count":84,"raw_metadata":null,"created_at":"2026-07-18T23:46:24.040760Z","pmid":"34860156","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}