{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T10:37:48Z","timestamp":1760783868833,"version":"3.40.4"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2014,12,1]],"date-time":"2014-12-01T00:00:00Z","timestamp":1417392000000},"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":[[2014,12]]},"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\">Candida albicans<\/jats:named-content>is a common cause of catheter-related bloodstream infections (CR-BSI), in part due to its strong propensity to form biofilms. Drug repurposing is an approach that might identify agents that are able to overcome antifungal drug resistance within biofilms. Quinacrine (QNC) is clinically active against the eukaryotic protozoan parasites<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium<\/jats:named-content>and<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Giardia<\/jats:named-content>. We sought to investigate the antifungal activity of QNC against<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. albicans<\/jats:named-content>biofilms.<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. albicans<\/jats:named-content>biofilms were incubated with QNC at serially increasing concentrations (4 to 2,048 \u03bcg\/ml) and assessed using a 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2<jats:italic>H<\/jats:italic>-tetrazolium-5-carboxanilide (XTT) assay in a static microplate model. Combinations of QNC and standard antifungals were assayed using biofilm checkerboard analyses. To define a mechanism of action, QNC was assessed for the inhibition of filamentation, effects on endocytosis, and pH-dependent activity. High-dose QNC was effective for the prevention and treatment of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. albicans<\/jats:named-content>biofilms<jats:italic>in vitro<\/jats:italic>. QNC with fluconazole had no interaction, while the combination of QNC and either caspofungin or amphotericin B demonstrated synergy. QNC was most active against planktonic growth at alkaline pH. QNC dramatically inhibited filamentation. QNC accumulated within vacuoles as expected and caused defects in endocytosis. A tetracycline-regulated<jats:italic>VMA3<\/jats:italic>mutant lacking vacuolar ATPase (V-ATPase) function demonstrated increased susceptibility to QNC. These experiments indicate that QNC is active against<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. albicans<\/jats:named-content>growth in a pH-dependent manner. Although QNC activity is not biofilm specific, QNC is effective in the prevention and treatment of biofilms. QNC antibiofilm activity likely occurs via several independent mechanisms: vacuolar alkalinization, inhibition of endocytosis, and impaired filamentation. Further investigation of QNC for the treatment and prevention of biofilm-related<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida<\/jats:named-content>CR-BSI is warranted.<\/jats:p>","DOI":"10.1128\/aac.03083-14","type":"journal-article","created":{"date-parts":[[2014,10,7]],"date-time":"2014-10-07T07:44:04Z","timestamp":1412667844000},"page":"7501-7509","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":33,"title":["Quinacrine Inhibits Candida albicans Growth and Filamentation at Neutral pH"],"prefix":"10.1128","volume":"58","author":[{"given":"Vibhati V.","family":"Kulkarny","sequence":"first","affiliation":[{"name":"Section of Infectious Diseases, New Mexico Veterans Health Care System, Albuquerque, New Mexico, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alba","family":"Chavez-Dozal","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, New Mexico Veterans Health Care System, Albuquerque, New Mexico, USA"},{"name":"Division of Infectious Diseases, University of New Mexico Health Science Center, Albuquerque, New Mexico, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hallie S.","family":"Rane","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, New Mexico Veterans Health Care System, Albuquerque, New Mexico, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maximillian","family":"Jahng","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, New Mexico Veterans Health Care System, Albuquerque, New Mexico, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stella M.","family":"Bernardo","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, New Mexico Veterans Health Care System, Albuquerque, New Mexico, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karlett J.","family":"Parra","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of New Mexico Health Science Center, Albuquerque, New Mexico, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel A.","family":"Lee","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, New Mexico Veterans Health Care System, Albuquerque, New Mexico, USA"},{"name":"Division of Infectious Diseases, University of New Mexico Health Science Center, Albuquerque, New Mexico, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.4.4.633-638.2005"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(02)00002-1"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.11.3657-3659.2003"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3109\/10408410903241436"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00856-07"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkp429"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01351-12"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.11.3499-3505.2002"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/1478-811X-9-13"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2013.04.004"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2012.106"},{"key":"e_1_3_3_13_2","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/S0190-9622(81)70065-3","article-title":"Antimalarials","volume":"4","author":"Koranda FC","year":"1981","unstructured":"KorandaFC. 1981. 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