{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:30:17Z","timestamp":1790573417073,"version":"4.1.0"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"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":[[2015,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            We report on the\n            <jats:italic>in vitro<\/jats:italic>\n            effects of the bumped kinase inhibitor 1294 (BKI-1294) in cultures of virulent\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Neospora caninum<\/jats:named-content>\n            isolates Nc-Liverpool (Nc-Liv) and Nc-Spain7 and in two strains of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Toxoplasma gondii<\/jats:named-content>\n            (RH and ME49), all grown in human foreskin fibroblasts. In these parasites, BKI-1294 acted with 50% inhibitory concentrations (IC\n            <jats:sub>50<\/jats:sub>\n            s) ranging from 20 nM (\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. gondii<\/jats:named-content>\n            RH) to 360 nM (\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">N. caninum<\/jats:named-content>\n            Nc-Liv), and exposure of intracellular stages to 1294 led to the nondisjunction of newly formed tachyzoites, resulting in the formation of multinucleated complexes similar to complexes previously observed in BKI-1294-treated\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">N. caninum<\/jats:named-content>\n            beta-galactosidase-expressing parasites. However, such complexes were not seen in a transgenic\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. gondii<\/jats:named-content>\n            strain that expressed CDPK1 harboring a mutation (G to M) in the gatekeeper residue. In\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. gondii<\/jats:named-content>\n            ME49 and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">N. caninum<\/jats:named-content>\n            Nc-Liv, exposure of cultures to BKI-1294 resulted in the elevated expression of mRNA coding for the bradyzoite marker BAG1. Unlike in bradyzoites, SAG1 expression was not repressed. Immunofluorescence also showed that these multinucleated complexes expressed SAG1 and BAG1 and the monoclonal antibody CC2, which binds to a yet unidentified bradyzoite antigen, also exhibited increased labeling. In a pregnant mouse model, BKI-1294 efficiently inhibited vertical transmission in BALB\/c mice experimentally infected with one of the two virulent isolates Nc-Liv or Nc-Spain7, demonstrating proof of concept that this compound protected offspring from vertical transmission and disease. The observed deregulated antigen expression effect may enhance the immune response during BKI-1294 therapy and will be the subject of future studies.\n          <\/jats:p>","DOI":"10.1128\/aac.01236-15","type":"journal-article","created":{"date-parts":[[2015,7,28]],"date-time":"2015-07-28T01:31:15Z","timestamp":1438047075000},"page":"6361-6374","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":87,"title":["<i>In Vitro<\/i>\n            and\n            <i>In Vivo<\/i>\n            Effects of the Bumped Kinase Inhibitor 1294 in the Related Cyst-Forming Apicomplexans Toxoplasma gondii and Neospora caninum"],"prefix":"10.1128","volume":"59","author":[{"given":"Pablo","family":"Winzer","sequence":"first","affiliation":[{"name":"Institute of Parasitology, Vetsuisse Faculty, University of Berne, Berne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, Vetsuisse Faculty, University of Berne, Berne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Aguado-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, Vetsuisse Faculty, University of Berne, Berne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahbubur","family":"Rahman","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, Vetsuisse Faculty, University of Berne, Berne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vreni","family":"Balmer","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, Vetsuisse Faculty, University of Berne, Berne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Manser","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, Vetsuisse Faculty, University of Berne, Berne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis Miguel","family":"Ortega-Mora","sequence":"additional","affiliation":[{"name":"SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Ciudad Universitaria, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayode K.","family":"Ojo","sequence":"additional","affiliation":[{"name":"Center for Emerging and Reemerging Infectious Diseases (CERID), Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erkang","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of 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