{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:40:23Z","timestamp":1791560423320,"version":"4.3.4"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2017,2,1]],"date-time":"2017-02-01T00:00:00Z","timestamp":1485907200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"United States Department of Veterans Affairs Biomedical Laboratory Research and Development","award":["BX002440"],"award-info":[{"award-number":["BX002440"]}]},{"name":"Peer Reviewed Medical Research Program Project","award":["PR130649"],"award-info":[{"award-number":["PR130649"]}]},{"DOI":"10.13039\/100000738","name":"United States Department of Veterans Affairs","doi-asserted-by":"crossref","award":["BX003312"],"award-info":[{"award-number":["BX003312"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI100569"],"award-info":[{"award-number":["R01 AI100569"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content content-type=\"genus-species\">Toxoplasma gondii<\/jats:named-content>\n            is an apicomplexan parasite that causes fatal and debilitating brain and eye disease. Endochinlike quinolones (ELQs) are preclinical compounds that are efficacious against apicomplexan-caused diseases, including toxoplasmosis, malaria, and babesiosis. Of the ELQs, ELQ-316 has demonstrated the greatest efficacy against acute and chronic experimental toxoplasmosis. Although genetic analyses in other organisms have highlighted the importance of the cytochrome\n            <jats:italic>bc<\/jats:italic>\n            <jats:sub>1<\/jats:sub>\n            complex Q\n            <jats:sub>i<\/jats:sub>\n            site for ELQ sensitivity, the mechanism of action of ELQs against\n            <jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>\n            and the specific mechanism of ELQ-316 remain unknown. Here, we describe the selection and genetic characterization of\n            <jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>\n            clones resistant to ELQ-316. A\n            <jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>\n            strain selected under ELQ-316 drug pressure was found to possess a Thr222-Pro amino acid substitution that confers 49-fold resistance to ELQ-316 and 19-fold resistance to antimycin, a well-characterized Q\n            <jats:sub>i<\/jats:sub>\n            site inhibitor. These findings provide further evidence for ELQ Q\n            <jats:sub>i<\/jats:sub>\n            site inhibition in\n            <jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>\n            and greater insight into the interactions of Q\n            <jats:sub>i<\/jats:sub>\n            site inhibitors with the apicomplexan cytochrome\n            <jats:italic>bc<\/jats:italic>\n            <jats:sub>1<\/jats:sub>\n            complex.\n          <\/jats:p>","DOI":"10.1128\/aac.01866-16","type":"journal-article","created":{"date-parts":[[2016,12,6]],"date-time":"2016-12-06T03:00:36Z","timestamp":1480993236000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":58,"title":["Genetic Evidence for Cytochrome\n            <i>b<\/i>\n            Q\n            <sub>i<\/sub>\n            Site Inhibition by 4(1\n            <i>H<\/i>\n            )-Quinolone-3-Diarylethers and Antimycin in Toxoplasma gondii"],"prefix":"10.1128","volume":"61","author":[{"given":"P. Holland","family":"Alday","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Oregon Health &amp; Science University, Portland, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4155-7596","authenticated-orcid":false,"given":"Igor","family":"Bruzual","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Portland VA Medical Center, Portland, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Nilsen","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Portland VA Medical Center, Portland, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sovitj","family":"Pou","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Portland VA Medical Center, Portland, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Winter","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Portland VA Medical Center, Portland, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Choukri","family":"Ben Mamoun","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael K.","family":"Riscoe","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Portland VA Medical Center, Portland, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Stone","family":"Doggett","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Oregon Health &amp; Science University, Portland, Oregon, USA"},{"name":"Department of Research and Development, Portland VA Medical Center, Portland, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-7519(00)00124-7"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2015.04.005"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2013.05.006"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/339551"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/322694"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2016.06.006"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1202018"},{"key":"e_1_3_3_9_2","unstructured":"Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. 2016. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention the National Institutes of Health and the HIV Medicine Association of the Infectious Diseases Society of America. http:\/\/aidsinfo.nih.gov\/contentfiles\/lvguidelines\/adult_oi.pdf. Accessed 17 July 2016."},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)55879-8"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1416611112"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm500147k"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1208069109"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20151519"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04149-14"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2013.05.008"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00486-12"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(00)00184-5"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-013-3296-4"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2005.05.053"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(03)00391-0"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi0341814"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.052704699"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.3791\/3807"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0092444"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh340"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/1745-6150-7-12"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.molbev.a003851"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.2307\/2408678"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msw054"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01866-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01866-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:41:47Z","timestamp":1645476107000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01866-16"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2]]},"references-count":29,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2017,2]]}},"alternative-id":["10.1128\/AAC.01866-16"],"URL":"https:\/\/doi.org\/10.1128\/aac.01866-16","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2]]},"assertion":[{"value":"2016-08-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-11-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-01-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01866-16"}}