{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T19:37:46Z","timestamp":1784403466661,"version":"3.55.0"},"reference-count":35,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2022YFD1800205"],"award-info":[{"award-number":["2022YFD1800205"]}]},{"name":"National Key Research and Development Program of China","award":["2023YFD1802400"],"award-info":[{"award-number":["2023YFD1802400"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The protozoan parasite Toxoplasma gondii transitions between acute (tachyzoite) and chronic (bradyzoite) stages, enabling lifelong persistence in hosts. Iron depletion triggers bradyzoite differentiation, with the phosphotyrosyl phosphatase activator (PTPA) identified as a key regulator. Here, we define PTPA\u2019s role in T. gondii pathogenesis. PTPA forms a ternary complex with PP2A A\/C subunits, validated by reciprocal pull-down assays. Depleting PTPA impaired tachyzoite proliferation, invasion, and gliding motility, while stress-induced bradyzoites exhibited defective cyst formation and vacuolar swelling. Metabolic dysregulation included amylopectin accumulation and lipid droplet proliferation. The PP2A inhibitor LB-100 phenocopied PTPA depletion, suppressing tachyzoite growth and bradyzoite differentiation. TgPTPA emerges as a linchpin coordinating PP2A activity, metabolic flux, and lifecycle transitions. Its dual roles in acute virulence and chronic persistence, combined with LB-100\u2019s efficacy, position the PTPA\u2013PP2A axis as a promising target for antitoxoplasmosis strategies.<\/jats:p>","DOI":"10.3390\/cells14110835","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T08:51:04Z","timestamp":1749027064000},"page":"835","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["PTPA Governs Stress-Responsive Differentiation and Metabolic Homeostasis in Toxoplasma gondii"],"prefix":"10.3390","volume":"14","author":[{"given":"Zhu","family":"Ying","sequence":"first","affiliation":[{"name":"National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China"},{"name":"Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China"},{"name":"National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuntong","family":"Wu","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China"},{"name":"Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China"},{"name":"National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqun","family":"Pei","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China"},{"name":"Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China"},{"name":"National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Shang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China"},{"name":"Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China"},{"name":"National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7309-0340","authenticated-orcid":false,"given":"Jing","family":"Liu","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China"},{"name":"Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China"},{"name":"National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Liu","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China"},{"name":"Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China"},{"name":"National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1016\/j.pt.2019.07.001","article-title":"Toxoplasma gondii\u00a0","volume":"35","author":"Lourido","year":"2019","journal-title":"Trends Parasitol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1111\/j.1574-6976.2011.00305.x","article-title":"Mechanisms of Toxoplasma gondii persistence and latency","volume":"36","author":"Sullivan","year":"2012","journal-title":"FEMS Microbiol. 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