{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T13:44:38Z","timestamp":1778852678995,"version":"3.51.4"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2013,11,1]],"date-time":"2013-11-01T00:00:00Z","timestamp":1383264000000},"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":[[2013,11]]},"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            is responsible for an expanding epidemic of serious infections in Western Canada and the Northwestern United States (Pacific Northwest). Some patients with these infections respond poorly to azole antifungals, and high azole MICs have been reported in Pacific Northwest\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            . In this study, multiple azoles (but not amphotericin B) had higher MICs for 25 Pacific Northwest\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            than for 34 non-Pacific Northwest\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            or 20\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Cryptococcus neoformans<\/jats:named-content>\n            strains. We therefore examined the roles in azole resistance of overexpression of or mutations in the gene (\n            <jats:italic>ERG11<\/jats:italic>\n            ) encoding the azole target enzyme.\n            <jats:italic>ERG11<\/jats:italic>\n            \/\n            <jats:italic>ACT1<\/jats:italic>\n            mRNA ratios were higher 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            than in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. neoformans<\/jats:named-content>\n            , but these ratios did not differ in Pacific Northwest and non-Pacific Northwest\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            strains, nor did they correlate with fluconazole MICs within any group. Three Pacific Northwest\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            strains with low azole MICs and 2 with high azole MICs had deduced Erg11p sequences that differed at one or more positions from that of the fully sequenced Pacific Northwest\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            strain R265. However, the azole MICs for conditional\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            <jats:italic>erg11<\/jats:italic>\n            mutants expressing the 5 variant\n            <jats:italic>ERG11<\/jats:italic>\n            s were within 2-fold of the azole MICs for\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. cerevisiae<\/jats:named-content>\n            expressing the\n            <jats:italic>ERG11<\/jats:italic>\n            gene from\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            R265, non-Pacific Northwest\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            strain WM276, or\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. neoformans<\/jats:named-content>\n            strains H99 or JEC21. We conclude that neither\n            <jats:italic>ERG11<\/jats:italic>\n            overexpression nor variations in\n            <jats:italic>ERG11<\/jats:italic>\n            coding sequences was responsible for the high azole MICs observed for the Pacific Northwest\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            strains we studied.\n          <\/jats:p>","DOI":"10.1128\/aac.02287-12","type":"journal-article","created":{"date-parts":[[2013,8,27]],"date-time":"2013-08-27T04:14:23Z","timestamp":1377576863000},"page":"5478-5485","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":40,"title":["Azole Resistance in Cryptococcus gattii from the Pacific Northwest: Investigation of the Role of\n            <i>ERG11<\/i>"],"prefix":"10.1128","volume":"57","author":[{"given":"Charles E.","family":"Gast","sequence":"first","affiliation":[{"name":"Infectious Diseases Division, Department of Medicine, Oregon Health and Science University, Portland, Oregon, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Luiz R.","family":"Basso","sequence":"additional","affiliation":[{"name":"Infectious Diseases Division, Department of Medicine, Oregon Health and Science University, Portland, Oregon, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor","family":"Bruzual","sequence":"additional","affiliation":[{"name":"Infectious Diseases Division, Department of Medicine, Oregon Health and Science University, Portland, Oregon, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Wong","sequence":"additional","affiliation":[{"name":"Infectious Diseases Division, Department of Medicine, Oregon Health and Science University, Portland, Oregon, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cir723"},{"key":"e_1_3_2_3_2","first-page":"865","article-title":"Emergence of Cryptococcus gattii\u2014Pacific Northwest, 2004\u20132010","volume":"59","author":"Centers for Disease Control and Prevention","year":"2010","unstructured":"Centers for Disease Control and Prevention. 2010. 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