{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:06:06Z","timestamp":1791252366885,"version":"4.1.0"},"reference-count":32,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2015,11,1]],"date-time":"2015-11-01T00:00:00Z","timestamp":1446336000000},"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":[[2015,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Toxoplasma gondii<\/jats:named-content>is a protozoan parasite that persists as a chronic infection.<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Toxoplasma<\/jats:named-content>evades immunity by forming tissue cysts, which reactivate to cause life-threatening disease during immune suppression. There is an urgent need to identify drugs capable of targeting these latent tissue cysts, which tend to form in the brain. We previously showed that translational control is critical during infections with both replicative and latent forms of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Toxoplasma<\/jats:named-content>. Here we report that guanabenz, an FDA-approved drug that interferes with translational control, has antiparasitic activity against replicative stages of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Toxoplasma<\/jats:named-content>and the related apicomplexan parasite<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium falciparum<\/jats:named-content>(a malaria agent). We also found that inhibition of translational control interfered with tissue cyst biology<jats:italic>in vitro<\/jats:italic>.<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Toxoplasma<\/jats:named-content>bradyzoites present in these abnormal cysts were diminished and misconfigured, surrounded by empty space not seen in normal cysts. These findings prompted analysis of the efficacy of guanabenz<jats:italic>in vivo<\/jats:italic>by using established mouse models of acute and chronic toxoplasmosis. In addition to protecting mice from lethal doses of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Toxoplasma<\/jats:named-content>, guanabenz has a remarkable ability to reduce the number of brain cysts in chronically infected mice. Our findings suggest that guanabenz can be repurposed into an effective antiparasitic with a unique ability to reduce tissue cysts in the brain.<\/jats:p>","DOI":"10.1128\/aac.01683-15","type":"journal-article","created":{"date-parts":[[2015,8,25]],"date-time":"2015-08-25T01:40:12Z","timestamp":1440466812000},"page":"6939-6945","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":69,"title":["Guanabenz Repurposed as an Antiparasitic with Activity against Acute and Latent Toxoplasmosis"],"prefix":"10.1128","volume":"59","author":[{"given":"Imaan","family":"Benmerzouga","sequence":"first","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, USA"},{"name":"Department of Biochemistry &amp; Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A.","family":"Checkley","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Ferdig","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Eck Institute for Global Health, University of Notre Dame, Notre Dame, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Arrizabalaga","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, USA"},{"name":"Department of Microbiology &amp; Immunology, 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 &amp; 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 &amp; Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, USA"},{"name":"Department of Microbiology &amp; Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1079\/AHR2005100"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2011.00305.x"},{"key":"e_1_3_2_4_2","first-page":"2131","article-title":"Congenital toxoplasmosis","volume":"67","author":"Jones J","year":"2003","unstructured":"Jones J, Lopez A, Wilson M. 2003. Congenital toxoplasmosis. 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