{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:58:02Z","timestamp":1790845082426,"version":"4.1.0"},"reference-count":38,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[1998,12,1]],"date-time":"1998-12-01T00:00:00Z","timestamp":912470400000},"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":[[1998,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            From each of two AIDS patients with oropharyngeal candidiasis, five\n            <jats:italic>Candida albicans<\/jats:italic>\n            isolates from recurrent episodes of infection which became gradually resistant against fluconazole during antimycotic treatment were analyzed for molecular changes responsible for drug resistance. In both patients, a single\n            <jats:italic>C. albicans<\/jats:italic>\n            strain was responsible for the recurrent infections, but the\n            <jats:italic>CARE-2<\/jats:italic>\n            fingerprint pattern of the isolates exhibited minor genetic alterations, indicating that microevolution of the strains took place during fluconazole therapy. In the isolates from patient 1, enhanced mRNA levels of the\n            <jats:italic>MDR1<\/jats:italic>\n            gene, encoding a multiple drug resistance protein from the superfamily of major facilitators, and constitutive high expression of the\n            <jats:italic>ERG11<\/jats:italic>\n            gene, coding for the drug target enzyme sterol 14\u03b1-demethylase, correlated with a stepwise development of fluconazole resistance. The resistant strains exhibited reduced accumulation of fluconazole and, for the last in the series, a slight increase in drug needed to inhibit sterol 14\u03b1-demethylation in vitro. In the isolates from patient 2, increased\n            <jats:italic>MDR1<\/jats:italic>\n            mRNA levels and the change from heterozygosity to homozygosity for a mutant form of the\n            <jats:italic>ERG11<\/jats:italic>\n            gene correlated with continuously decreased drug susceptibility. In this series, reduced drug accumulation and increased resistance in the target enzyme activity, sterol 14\u03b1-demethylase, were observed. These results demonstrate that different molecular mechanisms contribute to a gradual development of fluconazole resistance in\n            <jats:italic>C. albicans.<\/jats:italic>\n          <\/jats:p>","DOI":"10.1128\/aac.42.12.3065","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T00:29:51Z","timestamp":1539044991000},"page":"3065-3072","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":267,"title":["Multiple Molecular Mechanisms Contribute to a Stepwise Development of Fluconazole Resistance in Clinical\n            <i>Candida albicans<\/i>\n            Strains"],"prefix":"10.1128","volume":"42","author":[{"given":"Renate","family":"Franz","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Zentrum fu\u0308r Infektionsforschung, Universita\u0308t Wu\u0308rzburg, D-97070 Wu\u0308rzburg,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven L.","family":"Kelly","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Institute of Biological Sciences, University of Wales\u2014Aberystwyth, Aberystwyth, Wales, SY23 3DA, United Kingdom2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Lamb","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Institute of Biological Sciences, University of Wales\u2014Aberystwyth, Aberystwyth, Wales, SY23 3DA, United Kingdom2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane E.","family":"Kelly","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Institute of Biological Sciences, University of Wales\u2014Aberystwyth, Aberystwyth, Wales, SY23 3DA, United Kingdom2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Ruhnke","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->Charite\u0301Campus Virchow-Klinikum, Humboldt-Universita\u0308t Berlin, D-13353 Berlin,3 Germany, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Morschha\u0308user","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Zentrum fu\u0308r Infektionsforschung, Universita\u0308t Wu\u0308rzburg, D-97070 Wu\u0308rzburg,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.12.2835"},{"key":"e_1_3_2_3_2","unstructured":"Ausubel\n              F. 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A.\n              Struhl\n              K.\n          Current protocols in molecular biology.\n          1989\n          John Wiley & Sons Inc.\n          New York N.Y"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00259685"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/134.3.717"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.34.3.489-495.1996"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.2.422"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.14.7.4653-4661.1994"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.12.6875"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1042\/bst0211034"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.1272"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)65949-1"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(96)01360-9"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.179.7.2331-2338.1997"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/17.2.804"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.9.5682"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.1997.tb10303.x"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(92)90628-3"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.34.4.767-777.1996"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1097(97)00172-9"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/17.22.9488"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1996.tb02493.x"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.32.4.1115-1118.1994"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.17.9.5453"},{"key":"e_1_3_2_25_2","unstructured":"Odds\n              F. 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F.\n              Maniatis\n              T.\n          Molecular cloning: a laboratory manual\n          2nd ed.\n          1989\n          Cold Spring Harbor Laboratory Press\n          Cold Spring Harbor N.Y"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.11.2378"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.10.2300"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-143-2-405"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.2.241"},{"key":"e_1_3_2_34_2","unstructured":"Scherer\n              S.\n              Ran\n              Y.\n          Candida albicans information: webpage\n          1997\n          http:\/\/alces.med.umn.edu\/Candida.html"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.32.11.2646-2654.1994"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/0966-842X(94)90618-1"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.1995.tb07797.x"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.7.1482"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.7.1488"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.42.12.3065","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.42.12.3065","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T15:45:16Z","timestamp":1645458316000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.42.12.3065"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,12]]},"references-count":38,"journal-issue":{"issue":"12","published-print":{"date-parts":[[1998,12]]}},"alternative-id":["10.1128\/AAC.42.12.3065"],"URL":"https:\/\/doi.org\/10.1128\/aac.42.12.3065","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,12]]},"assertion":[{"value":"1997-09-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-09-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-12-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}