{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:08:51Z","timestamp":1791317331315,"version":"4.3.1"},"reference-count":26,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2013,4,1]],"date-time":"2013-04-01T00:00:00Z","timestamp":1364774400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2013,4]]},"abstract":"ABSTRACT<\/jats:title>\n \n Toxoplasma gondii<\/jats:named-content>\n is an obligate intracellular parasite that permanently infects warm-blooded vertebrates through its ability to convert into a latent tissue cyst form. The latent form (bradyzoite) can reinitiate a life-threatening acute infection if host immunity wanes, most commonly in AIDS or organ transplant patients. We have previously shown that bradyzoite development is accompanied by phosphorylation of the parasite eukaryotic initiation factor 2 alpha subunit (eIF2\u03b1), which dampens global protein synthesis and reprograms gene expression. In this study, we analyzed the activities of two specific inhibitors of eIF2\u03b1 dephosphorylation, salubrinal (SAL) and guanabenz (GA). We establish that these drugs are able to inhibit the dephosphorylation of\n Toxoplasma<\/jats:named-content>\n eIF2\u03b1. Our results show that SAL and GA reduce tachyzoite replication\n in vitro<\/jats:italic>\n and\n in vivo<\/jats:italic>\n . Furthermore, both drugs induce bradyzoite formation and inhibit the reactivation of latent bradyzoites\n in vitro<\/jats:italic>\n . To address whether the antiparasitic activities of SAL and GA involve host eIF2\u03b1 phosphorylation, we infected mutant mouse embryonic fibroblast (MEF) cells incapable of phosphorylating eIF2\u03b1, which had no impact on the efficacies of SAL and GA against\n Toxoplasma<\/jats:named-content>\n infection. Our findings suggest that SAL and GA may serve as potential new drugs for the treatment of acute and chronic toxoplasmosis.\n <\/jats:p>","DOI":"10.1128\/aac.01899-12","type":"journal-article","created":{"date-parts":[[2013,2,5]],"date-time":"2013-02-05T04:56:57Z","timestamp":1360040217000},"page":"1815-1822","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":51,"title":["Inhibitors of eIF2\u03b1 Dephosphorylation Slow Replication and Stabilize Latency in Toxoplasma gondii"],"prefix":"10.1128","volume":"57","author":[{"given":"Christian","family":"Konrad","sequence":"first","affiliation":[{"name":"Department of Biochemistry & Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA"},{"name":"Department of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherry F.","family":"Queener","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald C.","family":"Wek","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"William J.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, USA"},{"name":"Department of Microbiology & Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16412-X"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-010-1899-6"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2011.00305.x"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/22.2.268"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj20040262"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M800681200"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST0340007"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1586\/eri.10.146"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.05117-11"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1007610107"},{"key":"e_1_3_3_12_2","article-title":"Translational control in Plasmodium and Toxoplasma parasites","author":"Zhang M","year":"2012","unstructured":"ZhangM JoyceBR SullivanWJJr NussenzweigV. 14 December 2012. 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