{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T13:41:42Z","timestamp":1762004502778},"reference-count":44,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2013,8,1]],"date-time":"2013-08-01T00:00:00Z","timestamp":1375315200000},"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":[[2013,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Azoles are among the most successful classes of antifungals. They act by inhibiting \u03b1-14 lanosterol demethylase in the ergosterol biosynthesis pathway. Oropharyngeal candidiasis (OPC) occurs in about 90% of HIV-infected individuals, and 4 to 5% are refractory to current therapies, including azoles, due to the formation of resistant biofilms produced in the course of OPC. We reasoned that compounds affecting a different target may potentiate azoles to produce increased killing and an antibiofilm therapeutic. 2-Adamantanamine (AC17) was identified in a screen for compounds potentiating the action of miconazole against biofilms of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida albicans<\/jats:named-content>\n            . AC17, a close structural analog to the antiviral amantadine, did not affect the viability of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. albicans<\/jats:named-content>\n            but caused the normally fungistatic azoles to become fungicidal. Transcriptome analysis of cells treated with AC17 revealed that the ergosterol and filamentation pathways were affected. Indeed, cells exposed to AC17 had decreased ergosterol contents and were unable to invade agar.\n            <jats:italic>In vivo<\/jats:italic>\n            , the combination of AC17 and fluconazole produced a significant reduction in fungal tissue burden in a guinea pig model of cutaneous candidiasis, while each treatment alone did not have a significant effect. The combination of fluconazole and AC17 also showed improved efficacy (\n            <jats:italic>P<\/jats:italic>\n            value of 0.018) compared to fluconazole alone when fungal lesions were evaluated. AC17 is a promising lead in the search for more effective antifungal therapeutics.\n          <\/jats:p>","DOI":"10.1128\/aac.00294-13","type":"journal-article","created":{"date-parts":[[2013,5,21]],"date-time":"2013-05-21T05:04:18Z","timestamp":1369112658000},"page":"3585-3592","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":33,"title":["Potentiation of Azole Antifungals by 2-Adamantanamine"],"prefix":"10.1128","volume":"57","author":[{"given":"Michael D.","family":"LaFleur","sequence":"first","affiliation":[{"name":"Arietis Corporation, Boston, Massachusetts, USA"},{"name":"Antimicrobial Discovery Center and Department of Biology, Northeastern University, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingmei","family":"Sun","sequence":"additional","affiliation":[{"name":"Antimicrobial Discovery Center and Department of Biology, Northeastern University, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ida","family":"Lister","sequence":"additional","affiliation":[{"name":"Arietis Corporation, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Keating","sequence":"additional","affiliation":[{"name":"Arietis Corporation, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andre","family":"Nantel","sequence":"additional","affiliation":[{"name":"National Research Council of Canada, Montreal, QC, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Long","sequence":"additional","affiliation":[{"name":"Center for Medical Mycology, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahmoud","family":"Ghannoum","sequence":"additional","affiliation":[{"name":"Center for Medical Mycology, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"North","sequence":"additional","affiliation":[{"name":"Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard E.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Coleman","sequence":"additional","affiliation":[{"name":"Arietis Corporation, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Dahl","sequence":"additional","affiliation":[{"name":"Arietis Corporation, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim","family":"Lewis","sequence":"additional","affiliation":[{"name":"Antimicrobial Discovery Center and Department of Biology, Northeastern University, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/520192"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/511039"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1310\/T7A7-1E63-2KA0-JKWD"},{"issue":"4","key":"e_1_3_3_5_2","first-page":"1","article-title":"Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America","volume":"58","author":"Kaplan JE","year":"2009","unstructured":"KaplanJE BensonC HolmesKH BrooksJT PauA MasurH. 2009. 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