{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T12:56:56Z","timestamp":1782824216470,"version":"3.54.5"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | National Institutes of Health","award":["AI158417, AI124682"],"award-info":[{"award-number":["AI158417, AI124682"]}]},{"name":"HHS | National Institutes of Health","award":["AI122760"],"award-info":[{"award-number":["AI122760"]}]},{"name":"HHS | National Institutes of Health","award":["DA048815"],"award-info":[{"award-number":["DA048815"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2023,10,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The recrudescence of\n            <jats:italic>Toxoplasma<\/jats:italic>\n            cysts is the cause of clinical disease in the immunocompromised. Although\n            <jats:italic>Toxoplasma<\/jats:italic>\n            has been a useful parasite model for decades because it is relatively easy to genetically modify and culture, attempts to generate and study the recrudescence of tissue cysts have come up short with cell culture-adapted strains generating low numbers of tissue cysts\n            <jats:italic>in vivo<\/jats:italic>\n            . Taking advantage of a new\n            <jats:italic>ex vivo<\/jats:italic>\n            model of\n            <jats:italic>Toxoplasma<\/jats:italic>\n            recrudescence that uses a Type II ME49 strain unadapted to cell culture, we determined the cell biology, gene expression, and host cell dependency that define bradyzoite-cyst reactivation. Bradyzoite infection of fibroblasts and astrocytes produced sequential tachyzoite growth stages with pre-programmed kinetics; thus, an initial fast-growing stage was followed by a slow-growing replicating form.\n            <jats:italic>In vivo<\/jats:italic>\n            infections demonstrated that only fast growth tachyzoites, and not parasites post-growth shift, led to successful parasite dissemination to the brain and peripheral organs. In astrocytes, cells that reside in the central nervous system (CNS), bradyzoites initiated an additional recrudescent pathway involving brady-brady replication, which is a pathway not observed in fibroblasts. To investigate the molecular basis of growth and cell-dependent reactivation pathways, single-cell mRNA sequencing was performed on recrudescing parasites, revealing distinct gene signatures of these parasite populations and confirming multifunctionality of the original\n            <jats:italic>ex vivo<\/jats:italic>\n            bradyzoite population. This revised model of\n            <jats:italic>Toxoplasma<\/jats:italic>\n            recrudescence uncovers previously unknown complexity in the clinically important bradyzoite stage of the parasite, which opens the door to further study these novel developmental features of the\n            <jats:italic>Toxoplasma<\/jats:italic>\n            intermediate life cycle.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              The classical depiction of the\n              <jats:italic>Toxoplasma<\/jats:italic>\n              lifecycle is bradyzoite excystation conversion to tachyzoites, cell lysis, and immune control, followed by the reestablishment of bradyzoites and cysts. In contrast, we show that tachyzoite growth slows independent of the host immune response at a predictable time point following excystation. Furthermore, we demonstrate a host cell-dependent pathway of continuous amplification of the cyst-forming bradyzoite population. The developmental plasticity of the excysted bradyzoites further underlines the critical role the cyst plays in the flexibility of the lifecycle of this ubiquitous parasite. This revised model of\n              <jats:italic>Toxoplasma<\/jats:italic>\n              recrudescence uncovers previously unknown complexity in the clinically important bradyzoite stage of the parasite, which opens the door to further study these novel developmental features of the\n              <jats:italic>Toxoplasma<\/jats:italic>\n              intermediate life cycle.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.01836-23","type":"journal-article","created":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T13:01:52Z","timestamp":1694091712000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":20,"title":["An\n            <i>ex vivo<\/i>\n            model of\n            <i>Toxoplasma<\/i>\n            recrudescence reveals developmental plasticity of the bradyzoite stage"],"prefix":"10.1128","volume":"14","author":[{"given":"Edward A.","family":"Vizcarra","sequence":"first","affiliation":[{"name":"Division of Biomedical Sciences, School of Medicine, University of California , Riverside, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber L.","family":"Goerner","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease and International Medicine, Department of Internal Medicine, Morsani College of Medicine, University of South Florida , Tampa, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arzu","family":"Ulu","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, School of Medicine, University of California , Riverside, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David D.","family":"Hong","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease and International Medicine, Department of Internal Medicine, Morsani College of Medicine, University of South Florida , Tampa, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina V.","family":"Bergersen","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, School of Medicine, University of California , Riverside, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Talavera","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease and International Medicine, Department of Internal Medicine, Morsani College of Medicine, University of South Florida , Tampa, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"Le Roch","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell, and Systems Biology, University of California , Riverside, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6054-9981","authenticated-orcid":false,"given":"Emma H.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, School of Medicine, University of California , Riverside, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9727-4280","authenticated-orcid":false,"given":"Michael W.","family":"White","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease and International Medicine, Department of Internal Medicine, Morsani College of Medicine, University of South Florida , Tampa, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1017\/s0031182097008949"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1550-7408.1976.tb03836.x"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2009.02.004"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197310252891702"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-018-5950-3"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2007.06.003"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03035408"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1645\/0022-3395(2000)086[0531:ISCTIE]2.0.CO;2"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.35.6.1411-1414.1997"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","unstructured":"Hong DD Brooks K Goerner AL Vizcarra EA Loges LN Wilson EH White MW . 2022. 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