{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T01:50:38Z","timestamp":1777600238169,"version":"3.51.4"},"reference-count":50,"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            Chloroquine (CQ) has been a mainstay of antimalarial drug treatment for several decades. Additional therapeutic actions of CQ have been described, including some reports of fungal inhibition. Here we investigated the action of CQ in fungi, including the yeast model\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Saccharomyces cerevisiae<\/jats:named-content>\n            . A genomewide yeast deletion strain collection was screened against CQ, revealing that\n            <jats:italic>bck1<\/jats:italic>\n            \u0394 and\n            <jats:italic>slt2<\/jats:italic>\n            \u0394 mutants of the cell wall integrity pathway are CQ hypersensitive. This phenotype was rescued with sorbitol, consistent with cell wall involvement. The cell wall-targeting agent caffeine caused hypersensitivity to CQ, as did cell wall perturbation by sonication. The phenotypes were not caused by CQ-induced changes to cell wall components. Instead, CQ accumulated to higher levels in cells with perturbed cell walls: CQ uptake was 2- to 3-fold greater in\n            <jats:italic>bck1<\/jats:italic>\n            \u0394 and\n            <jats:italic>slt2<\/jats:italic>\n            \u0394 mutants than in wild-type yeast. CQ toxicity was synergistic with that of the major cell wall-targeting antifungal drug, caspofungin. The MIC of caspofungin against the yeast pathogen\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            was decreased 2-fold by 250 \u03bcM CQ and up to 8-fold at higher CQ concentrations. Similar effects were seen in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Candida glabrata<\/jats:named-content>\n            and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Aspergillus fumigatus<\/jats:named-content>\n            . The results show that the cell wall is critical for CQ resistance in fungi and suggest that combination treatments with cell wall-targeting drugs could have potential for antifungal treatment.\n          <\/jats:p>","DOI":"10.1128\/aac.00478-13","type":"journal-article","created":{"date-parts":[[2013,6,4]],"date-time":"2013-06-04T00:46:00Z","timestamp":1370306760000},"page":"3889-3896","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":31,"title":["Cell Wall Perturbation Sensitizes Fungi to the Antimalarial Drug Chloroquine"],"prefix":"10.1128","volume":"57","author":[{"given":"Farida","family":"Islahudin","sequence":"first","affiliation":[{"name":"School of Biology, University of Nottingham, Nottingham, United Kingdom"},{"name":"School of Pharmacy, University of Nottingham Malaysia Campus, Semenyih, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Combiz","family":"Khozoie","sequence":"additional","affiliation":[{"name":"School of Biology, University of Nottingham, Nottingham, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Bates","sequence":"additional","affiliation":[{"name":"University of Exeter, College of Life &amp; Environmental Sciences, Exeter, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kang-Nee","family":"Ting","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, University of Nottingham Malaysia Campus, Semenyih, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J.","family":"Pleass","sequence":"additional","affiliation":[{"name":"University of Liverpool, Liverpool School of Tropical Medicine, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon V.","family":"Avery","sequence":"additional","affiliation":[{"name":"School of Biology, University of Nottingham, Nottingham, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00029-06"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.46548-0"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.3.693-715.2004"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0307490100"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0036021"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.005843"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)01035-3"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dks253"},{"key":"e_1_3_3_10_2","volume-title":"Guidelines for the treatment of malaria","author":"WHO","year":"2010","unstructured":"WHO. 2010. 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