{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:24:34Z","timestamp":1791239074957,"version":"4.1.0"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2016,3,1]],"date-time":"2016-03-01T00:00:00Z","timestamp":1456790400000},"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":[[2016,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Cryptococcus gattii<\/jats:named-content>\n            isolates from the Pacific Northwest have exhibited higher fluconazole MICs than isolates from other sites. The mechanism of fluconazole resistance in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. gattii<\/jats:named-content>\n            is unknown. We sought to determine the role of the efflux pumps Mdr1 and Pdr11 in fluconazole susceptibility. Using biolistic transformation of the parent isolate, we created a strain lacking Mdr1 (\n            <jats:italic>mdr1<\/jats:italic>\n            \u0394) and another strain lacking Pdr11 (\n            <jats:italic>pdr11<\/jats:italic>\n            \u0394). Phenotypic virulence factors were assessed by standard methods (capsule size, melanin production, growth at 30 and 37\u00b0C). Survival was assessed in an intranasal murine model of cryptococcosis. Antifungal MICs were determined by the M27-A3 methodology. No differences in key virulence phenotypic components were identified. Fluconazole susceptibility was unchanged in the Mdr1 knockout or reconstituted isolates. However, fluconazole MICs decreased from 32 \u03bcg\/ml for the wild-type isolate to &lt;0.03 \u03bcg\/ml for the\n            <jats:italic>pdr11<\/jats:italic>\n            \u0394 strain and reverted to 32 \u03bcg\/ml for the reconstituted strain. In murine models, no difference in virulence was observed between wild-type, knockout, or reconstituted isolates. We conclude that Pdr11 plays an essential role in fluconazole susceptibility in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. gattii<\/jats:named-content>\n            . Genomic and expression differences between resistant and susceptible\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. gattii<\/jats:named-content>\n            clinical isolates should be assessed further in order to identify other potential mechanisms of resistance.\n          <\/jats:p>","DOI":"10.1128\/aac.01777-15","type":"journal-article","created":{"date-parts":[[2015,12,8]],"date-time":"2015-12-08T15:05:43Z","timestamp":1449587143000},"page":"1202-1207","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["Fluconazole Susceptibility in Cryptococcus gattii Is Dependent on the ABC Transporter Pdr11"],"prefix":"10.1128","volume":"60","author":[{"given":"Mai Lee","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Coccidioidomycosis Serology Laboratory, University of California\u2014Davis, Davis, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Uhrig","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of California, Genome and Biomedical Sciences Facility, Davis, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiem","family":"Vu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of California, Genome and Biomedical Sciences Facility, Davis, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Singapuri","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Coccidioidomycosis Serology Laboratory, University of California\u2014Davis, Davis, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Dennis","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Coccidioidomycosis Serology Laboratory, University of California\u2014Davis, Davis, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3351-0683","authenticated-orcid":false,"given":"Angie","family":"Gelli","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of California, Genome and Biomedical Sciences Facility, Davis, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"George R.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Coccidioidomycosis Serology Laboratory, University of California\u2014Davis, Davis, California, USA"},{"name":"Department of Internal Medicine, Division of Infectious Diseases, University of California\u2014Davis Medical Center, University of California\u2014Davis, Davis, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.13.123"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1601.090369"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dks060"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1301.060827"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002205"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005851"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1910.130441"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1810.120068"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1086\/649858"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01115-12"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00746-10"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2012.02.018"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01505-09"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.11.3653-3656.2003"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05502-11"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(95)00684-2"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033022"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000848"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00051-08"},{"key":"e_1_3_3_21_2","volume-title":"CLSI document M27-A3","author":"Clinical and Laboratory Standards Institute","year":"2008","unstructured":"Clinical and Laboratory Standards Institute. 2008. 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