{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:42:40Z","timestamp":1792114960256,"version":"4.4.0"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2018,12,4]],"date-time":"2018-12-04T00:00:00Z","timestamp":1543881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/AuthorWarrantyLicense.v1"},{"start":{"date-parts":[[2018,12,21]],"date-time":"2018-12-21T00:00:00Z","timestamp":1545350400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000052","name":"HHS | NIH | NIH Office of the Director","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"HHS | NIH | NIH Office of the Director","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"HHS | NIH | NIH Office of the Director","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2018,12,21]]},"abstract":"<jats:p>\n                    The gold standard of cryptococcosis treatment consists of induction therapy with amphotericin B followed by lifelong maintenance therapy with fluconazole (FLC). However, prolonged exposure to FLC induces the emergence of clones heteroresistant to azoles. All the heteroresistant clones thus far analyzed have been shown to be aneuploids, but how the aneuploid is formed remains unclear. Aneuploidy in fungi and other eukaryotic cells is known to result most commonly from chromosome missegregation during cell division due to defects in any one of the multiple components and processes that are required for the formation of two genetically identical daughter cells. Although formation of multinucleated cells has been observed in cells exposed to FLC, evidence for the emergence of drug-resistant aneuploid populations directly from such cells has been lacking. We show the evidence that the aneuploid in fluconazole-heteroresistant clones of\n                    <jats:named-content content-type=\"genus-species\">Cryptococcus neoformans<\/jats:named-content>\n                    is derived neither from multinucleated cells nor from chromosome missegregation.\n                  <\/jats:p>","DOI":"10.1128\/mbio.01290-18","type":"journal-article","created":{"date-parts":[[2018,12,3]],"date-time":"2018-12-03T06:08:31Z","timestamp":1543817311000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":33,"title":["Cryptococcus neoformans, Unlike Candida albicans, Forms Aneuploid Clones Directly from Uninucleated Cells under Fluconazole Stress"],"prefix":"10.1128","volume":"9","author":[{"given":"Yun C.","family":"Chang","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ami","family":"Khanal Lamichhane","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung J.","family":"Kwon-Chung","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a019760"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30243-8"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/649858"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00295-09"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000848"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1128242"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/femsyr\/fow020"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001815"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00205-17"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.108.090878"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003022"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/1574-6976.12048"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1215"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.1.2.114"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0084645"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.11.2.382"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.1992.tb00001.x"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.07.046"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00145-06"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/28.6.491"},{"key":"e_1_3_2_22_2","first-page":"28","article-title":"The fidelity of mitotic chromosome reproduction in S. cerevisiae","volume":"1","author":"Hartwell LH","year":"1982","unstructured":"Hartwell LH, Dutcher SK, Wood JS, Garvik B. 1982. The fidelity of mitotic chromosome reproduction in S. cerevisiae. Rec Adv Yeast Mol Biol 1:28\u201338.","journal-title":"Rec Adv Yeast Mol Biol"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10795"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12940-016-0180-6"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(10)70021-5"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-313x.2000.00868.x"},{"key":"e_1_3_2_27_2","unstructured":"CLSI. 2008. Reference method for broth dilution antifungal susceptibility testing of yeasts\u20143rd ed approved standard M27-A3. CLSI Wayne PA."},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1080\/02681219680000521"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2012.08.015"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp253"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.01290-18","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.01290-18","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T21:43:14Z","timestamp":1646689394000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mBio.01290-18"}},"subtitle":[],"editor":[{"given":"J. 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