{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:24:05Z","timestamp":1791239045701,"version":"4.1.0"},"reference-count":30,"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":"<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 neoformans<\/jats:named-content>\n                    strains resistant to azoles due to mutations causing alterations in the\n                    <jats:italic>ERG11<\/jats:italic>\n                    gene, encoding lanosterol 14\u03b1-demethylase, have rarely been reported. In this study, we have characterized a\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                    serotype A strain that is resistant to high concentrations of fluconazole (FLC). This strain, which was isolated from an FLC-treated patient, contained five missense mutations in the\n                    <jats:italic>ERG11<\/jats:italic>\n                    gene compared to the sequence of reference strain H99. Molecular manipulations of the\n                    <jats:italic>ERG11<\/jats:italic>\n                    gene coupled with susceptibility to triazole revealed that a single missense mutation resulting in the replacement of tyrosine by phenylalanine at amino acid 145 was sufficient to cause the high FLC resistance of the strain. Importantly, this newly identified point mutation in the\n                    <jats:italic>ERG11<\/jats:italic>\n                    gene of\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                    afforded resistance to voriconazole (VRC) but increased susceptibility to itraconazole (ITC) and posaconazole (PSC), which are structurally similar to each other but distinct from FLC\/VRC. The\n                    <jats:italic>in vitro<\/jats:italic>\n                    susceptibility\/resistance of the strains with or without the missense mutation was reflected in the therapeutic efficacy of FLC versus ITC in the animals infected with the strains. This study shows the importance of the Y145F alteration of Erg11 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                    for manifestation of differential susceptibility toward different triazoles. It underscores the necessity of\n                    <jats:italic>in vitro<\/jats:italic>\n                    susceptibility testing for each FLC-resistant\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                    clinical isolate against different groups of azoles in order to assist patient management.\n                  <\/jats:p>","DOI":"10.1128\/aac.05502-11","type":"journal-article","created":{"date-parts":[[2011,12,13]],"date-time":"2011-12-13T00:21:18Z","timestamp":1323735678000},"page":"1162-1169","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":120,"title":["Identification of a Cryptococcus neoformans Cytochrome P450 Lanosterol 14\u03b1-Demethylase (Erg11) Residue Critical for Differential Susceptibility between Fluconazole\/Voriconazole and Itraconazole\/Posaconazole"],"prefix":"10.1128","volume":"56","author":[{"given":"Edward","family":"Sionov","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun C.","family":"Chang","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Martin","family":"Garraffo","sequence":"additional","affiliation":[{"name":"Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive &amp; Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Dolan","sequence":"additional","affiliation":[{"name":"Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud A.","family":"Ghannoum","sequence":"additional","affiliation":[{"name":"Center for Medical Mycology, Case Western Reserve University, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung J.","family":"Kwon-Chung","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1093\/clinids\/23.6.1337-a","article-title":"Possible development of resistance to fluconazole during suppressive therapy for AIDS-associated cryptococcal meningitis","volume":"23","author":"Armengou A","year":"1996","unstructured":"ArmengouA PorcarC MascaroJ Garcia-BragadoF. 1996. Possible development of resistance to fluconazole during suppressive therapy for AIDS-associated cryptococcal meningitis. Clin. Infect. Dis. 23:1337\u20131338.","journal-title":"Clin. Infect. Dis"},{"key":"e_1_3_3_3_2","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1046\/j.1469-0691.2003.00571.x","article-title":"Cryptococcus neoformans var neoformans resistant to fluconazole in an HIV-negative patient with chronic lymphocytic leukemia","volume":"9","author":"Assing K","year":"2003","unstructured":"AssingK BirgensH ArendrupM. 2003. Cryptococcus neoformans var neoformans resistant to fluconazole in an HIV-negative patient with chronic lymphocytic leukemia. Clin. Microbiol. Infect. 9:441\u2013444.","journal-title":"Clin. Microbiol. 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Biochemistry 42:9091\u20139101.","journal-title":"Biochemistry"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.2.577-581.2003"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.8.1856"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2009.11.006"},{"key":"e_1_3_3_18_2","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.abb.2008.11.003","article-title":"Sterol 24-C-methyltransferase: an enzymatic target for the disruption of ergosterol biosynthesis and homeostasis in Cryptococcus neoformans","volume":"481","author":"Nes WD","year":"2009","unstructured":"NesWD. 2009. Sterol 24-C-methyltransferase: an enzymatic target for the disruption of ergosterol biosynthesis and homeostasis in Cryptococcus neoformans. Arch. Biochem. Biophys. 481:210\u2013218.","journal-title":"Arch. Biochem. 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