{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:47:59Z","timestamp":1792100879996,"version":"4.4.0"},"reference-count":60,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T00:00:00Z","timestamp":1726012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T00:00:00Z","timestamp":1726012800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | National Institutes of Health","award":["AI162749"],"award-info":[{"award-number":["AI162749"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2024,9,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              <jats:italic>Toxoplasma gondii<\/jats:italic>\n              bradyzoites play a critical role in pathology due to their long-term persistence in intermediate hosts and their potential to reactivate, resulting in severe diseases in immunocompromised individuals. Currently, there is no effective treatment for eliminating bradyzoites. Hence, better\n              <jats:italic>in vitro<\/jats:italic>\n              models of\n              <jats:italic>T. gondii<\/jats:italic>\n              bradyzoite development would facilitate identification of therapeutic targets for bradyzoites. Herein, we characterized a natural isolate of\n              <jats:italic>T. gondii<\/jats:italic>\n              , called Tg68, which showed slower\n              <jats:italic>in vitro<\/jats:italic>\n              replication of tachyzoites, and permissive bradyzoite development under stress conditions\n              <jats:italic>in vitro<\/jats:italic>\n              . Transcriptional analysis revealed constitutive expression in Tg68 tachyzoites of the key regulators of bradyzoite development including\n              <jats:italic>BFD1<\/jats:italic>\n              ,\n              <jats:italic>BFD2<\/jats:italic>\n              , and several AP2 factors. Consistent with this finding, Tg68 tachyzoites expressed high levels of bradyzoite-specific genes including\n              <jats:italic>BAG1<\/jats:italic>\n              ,\n              <jats:italic>ENO1<\/jats:italic>\n              , and\n              <jats:italic>LDH2<\/jats:italic>\n              . Moreover, after stress-induced differentiation, Tg68 bradyzoites exhibited gene expression profiles of mature bradyzoites, even at early time points. These data suggest that Tg68 tachyzoites exist in a pre-bradyzoite stage primed to readily develop into mature bradyzoites under stress conditions\n              <jats:italic>in vitro<\/jats:italic>\n              . Tg68 presents a novel model for differentiation\n              <jats:italic>in vitro<\/jats:italic>\n              that will serve as a useful tool for the investigation of bradyzoite biology and the development of therapeutics.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              <jats:italic>Toxoplasma gondii<\/jats:italic>\n              is a widespread protozoan that chronically infects ~30% of the world\u2019s population.\n              <jats:italic>T. gondii<\/jats:italic>\n              can differentiate between the fast-growing life stage that causes acute infection and the slow-growing stage that persists in the host for extended periods of time. The slow-growing stage cannot be eliminated by the host immune response or currently known antiparasitic drugs. Studies on the slow-growing stage have been limited due to the limitations of\n              <jats:italic>in vivo<\/jats:italic>\n              experiments and the challenges of\n              <jats:italic>in vitro<\/jats:italic>\n              manipulation. Here, we characterize a natural isolate of\n              <jats:italic>T. gondii<\/jats:italic>\n              , which constitutively expresses factors that drive development and that is permissive to convert to the slow-growing stage under stress conditions\n              <jats:italic>in vitro<\/jats:italic>\n              . The strain presents a novel\n              <jats:italic>in vitro<\/jats:italic>\n              model for studying the chronic phase of toxoplasmosis and identifying new therapeutic treatments for chronic infections.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.00641-24","type":"journal-article","created":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T13:00:57Z","timestamp":1723813257000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Constitutive upregulation of transcription factors underlies permissive bradyzoite differentiation in a natural isolate of\n            <i>Toxoplasma gondii<\/i>"],"prefix":"10.1128","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7590-4544","authenticated-orcid":false,"given":"Jing","family":"Xia","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7590-4544","authenticated-orcid":false,"given":"Yong","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanyi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taher","family":"Uddin","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7110-0285","authenticated-orcid":true,"given":"L. 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