{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:59:21Z","timestamp":1790801961802,"version":"4.1.0"},"posted":{"date-parts":[[2024,2,29]]},"group-title":"Microbiology","reference-count":61,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,2,28]]},"abstract":"<jats:title>Abstract<\/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                  cyst 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 investigation of bradyzoite biology and development of therapeutics.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    is a widespread protozoan that chronically infects \u223c30% 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":"10.1101\/2024.02.28.582596","type":"posted-content","created":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T16:00:14Z","timestamp":1709222414000},"source":"Crossref","is-referenced-by-count":3,"title":["Constitutive upregulation of transcription factors underlies permissive bradyzoite differentiation in a natural isolate of\n                  <i>Toxoplasma gondii<\/i>"],"prefix":"10.64898","author":[{"given":"Jing","family":"Xia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanyi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. 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