{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:44:57Z","timestamp":1785422697252,"version":"3.56.0"},"reference-count":72,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1R21AI162606"],"award-info":[{"award-number":["1R21AI162606"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSphere"],"published-print":{"date-parts":[[2025,9,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Apicomplexan AP2 (ApiAP2) family proteins are a family of transcription factors that are known to regulate gene expression in apicomplexan pathogens, including\n                      <jats:italic toggle=\"yes\">Toxoplasma<\/jats:italic>\n                      . In this study, we focused on TgAP2X-7, a member of the APiAP2 family that is predicted to be essential for\n                      <jats:italic toggle=\"yes\">Toxoplasma<\/jats:italic>\n                      fitness. Endogenous tagging of TgAP2X-7 followed by immunofluorescence analysis revealed that it\u2019s a cell cycle-regulated nuclear protein with peak expression in the G1 phase. Since TgAP2X-7 is predicted to be essential for parasite growth, we adopted an auxin-inducible degron (AID) based conditional knockdown approach to understand its function. Phenotypic analysis of the conditional knockdown mutant of TgAP2X-7 showed that the protein is indeed essential for\n                      <jats:italic toggle=\"yes\">Toxoplasma<\/jats:italic>\n                      propagation\n                      <jats:italic toggle=\"yes\">in vitro,<\/jats:italic>\n                      and loss of this transcription factor results in a major defect in invasion and a minor defect in replication. Examination with cell division markers indicated that the absence of TgAP2X-7 results in defects in endodyogeny. Transcriptomic analysis indicated that loss of TgAP2X-7 leads to dysregulation of global gene expression in the parasite, including genes required for host-cell invasion, metabolism, and gene expression. Additionally, Cleavage Under Targets and Tagmentation (CUT&amp;TAG) analysis suggests that TgAP2X-7 likely binds to an 11 bp motif [C\/T\/G]GCATGCA[G\/C\/A][C\/T\/G][G\/A] in the parasite genes\u2019 promoter region. Together, these findings suggest that TgAP2X-7 is a novel transcriptional regulator in\n                      <jats:italic toggle=\"yes\">Toxoplasma<\/jats:italic>\n                      that governs the expression of genes required for parasite propagation.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Toxoplasma gondii<\/jats:italic>\n                        is a protozoan parasite that can cause life-threatening disease in mammals; hence, identifying key factors required for parasite growth and pathogenesis is important to develop novel therapeutics. In this study, we identify and characterize a member of the Apicomplexan AP2 (ApiAP2) family, TgAP2X-7, a developmentally regulated transcription factor. By generating conditional mutant TgAP2X-7, we show that this protein is required for\n                        <jats:italic toggle=\"yes\">Toxoplasma<\/jats:italic>\n                        propagation\n                        <jats:italic toggle=\"yes\">in vitro,<\/jats:italic>\n                        and the absence of this protein results in parasites with significantly reduced competency in invasion, moderate deficiency in replication, and defects in cell division. Importantly, TgAP2X-7-deficient parasites show global changes in gene expression profile, including decreased expression of genes important for\n                        <jats:italic toggle=\"yes\">Toxoplasma<\/jats:italic>\n                        entry into the host cell. Additionally, we identified an 11 bp DNA motif likely recognized by this transcription factor. Hence, this study provides an initial insight into the function of a novel cell cycle-regulated transcription factor essential for\n                        <jats:italic toggle=\"yes\">Toxoplasma<\/jats:italic>\n                        growth.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/msphere.00438-25","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T13:55:10Z","timestamp":1757339710000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["TgAP2X-7 is a novel cell cycle-regulated transcription factor that plays an essential role in\n                    <i>Toxoplasma<\/i>\n                    tachyzoite propagation"],"prefix":"10.1128","volume":"10","author":[{"given":"Padmaja","family":"Mandadi","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/010prmy50","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine","place":["Blacksburg, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramu","family":"Anandakrishnan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/010prmy50","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine","place":["Blacksburg, USA"]},{"id":[{"id":"https:\/\/ror.org\/00sda2672","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biomedical Sciences, Edward Via College of Osteopathic Medicine (VCOM)","place":["Blacksburg, 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