{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:09:57Z","timestamp":1790402997835,"version":"4.1.0"},"reference-count":54,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2012,3,1]],"date-time":"2012-03-01T00:00:00Z","timestamp":1330560000000},"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":[[2012,3]]},"abstract":"ABSTRACT<\/jats:title>\n \n Resistance to the commonly used azole antifungal fluconazole (FLC) can develop due to overexpression of ATP-binding cassette (ABC) and major facilitator superfamily (MFS) plasma membrane transporters. An approach to overcoming this resistance is to identify inhibitors of these efflux pumps. We have developed a pump assay suitable for high-throughput screening (HTS) that uses recombinant\n Saccharomyces cerevisiae<\/jats:named-content>\n strains hyperexpressing individual transporters from the opportunistic fungal pathogen\n Candida albicans<\/jats:named-content>\n . The recombinant strains possess greater resistance to azoles and other pump substrates than the parental host strain. A flow cytometry-based HTS, which measured increased intracellular retention of the fluorescent pump substrate rhodamine 6G (R6G) within yeast cells, was used to screen the Prestwick Chemical Library (PCL) of 1,200 marketed drugs. Nine compounds were identified as hits, and the monoamine oxidase A inhibitor (MAOI) clorgyline was identified as an inhibitor of two\n C. albicans<\/jats:named-content>\n ABC efflux pumps, CaCdr1p and CaCdr2p. Secondary\n in vitro<\/jats:italic>\n assays confirmed inhibition of pump-mediated efflux by clorgyline. Clorgyline also reversed the FLC resistance of\n S. cerevisiae<\/jats:named-content>\n strains expressing other individual fungal ABC transporters (\n Candida glabrata<\/jats:named-content>\n Cdr1p or\n Candida krusei<\/jats:named-content>\n Abc1p) or the\n C. albicans<\/jats:named-content>\n MFS transporter Mdr1p. Recombinant strains were also chemosensitized by clorgyline to other azoles (itraconazole and miconazole). Importantly, clorgyline showed synergy with FLC against FLC-resistant\n C. albicans<\/jats:named-content>\n clinical isolates and a\n C. glabrata<\/jats:named-content>\n strain and inhibited R6G efflux from a FLC-resistant\n C. albicans<\/jats:named-content>\n clinical isolate. Clorgyline is a novel broad-spectrum inhibitor of two classes of fungal efflux pumps that acts synergistically with azoles against azole-resistant\n C. albicans<\/jats:named-content>\n and\n C. glabrata<\/jats:named-content>\n strains.\n <\/jats:p>","DOI":"10.1128\/aac.05706-11","type":"journal-article","created":{"date-parts":[[2011,12,27]],"date-time":"2011-12-27T22:39:59Z","timestamp":1325025599000},"page":"1508-1515","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":103,"title":["The Monoamine Oxidase A Inhibitor Clorgyline Is a Broad-Spectrum Inhibitor of Fungal ABC and MFS Transporter Efflux Pump Activities Which Reverses the Azole Resistance of Candida albicans and Candida glabrata Clinical Isolates"],"prefix":"10.1128","volume":"56","author":[{"given":"Ann R.","family":"Holmes","sequence":"first","affiliation":[{"name":"Sir John Walsh Research Institute and Department of Oral Sciences, University of Otago, Dunedin, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail V.","family":"Keniya","sequence":"additional","affiliation":[{"name":"Sir John Walsh Research Institute and Department of Oral Sciences, University of Otago, Dunedin, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irena","family":"Ivnitski-Steele","sequence":"additional","affiliation":[{"name":"New Mexico Center for Molecular Discovery, University of New Mexico, Albuquerque, New Mexico, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian C.","family":"Monk","sequence":"additional","affiliation":[{"name":"Sir John Walsh Research Institute and Department of Oral Sciences, University of Otago, Dunedin, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwin","family":"Lamping","sequence":"additional","affiliation":[{"name":"Sir John Walsh Research Institute and Department of Oral Sciences, University of Otago, Dunedin, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry A.","family":"Sklar","sequence":"additional","affiliation":[{"name":"New Mexico Center for Molecular Discovery, University of New Mexico, Albuquerque, New Mexico, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D.","family":"Cannon","sequence":"additional","affiliation":[{"name":"Sir John Walsh Research Institute and Department of Oral Sciences, University of Otago, Dunedin, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1093\/jac\/dkg217","article-title":"Identification of genes differentially expressed in association with reduced azole susceptibility in Saccharomyces cerevisiae","volume":"51","author":"Barker KS","year":"2003","unstructured":"BarkerKS PearsonMM RogersPD. 2003. 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