{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:49:47Z","timestamp":1790434187282,"version":"4.1.0"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2002,6,1]],"date-time":"2002-06-01T00:00:00Z","timestamp":1022889600000},"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":[[2002,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Candida dubliniensis<\/jats:italic>\n            is a newly identified species of\n            <jats:italic>Candida<\/jats:italic>\n            that is phenotypically similar to but genetically distinct from\n            <jats:italic>C. albicans<\/jats:italic>\n            . This organism has been recovered with increasing frequency from the oral cavities of human immunodeficiency virus (HIV)-infected and AIDS patients and has been implicated as a causative agent of oral candidiasis and systemic disease. In the present study we characterized the molecular mechanisms of resistance to fluconazole (FLC) in\n            <jats:italic>C. dubliniensis<\/jats:italic>\n            clinical isolates from two different HIV-infected patients with oropharyngeal candidiasis. Isolates were identified to the species level by phenotypic and genotypic tests. DNA-typing techniques were used to assess strain identity. Antifungal susceptibility testing was performed by NCCLS techniques. Northern blotting analysis was used to monitor the expression of genes encoding lanosterol demethylase (\n            <jats:italic>ERG11<\/jats:italic>\n            ) and efflux transporters (\n            <jats:italic>CDR<\/jats:italic>\n            and\n            <jats:italic>MDR1<\/jats:italic>\n            ) in matched sets of\n            <jats:italic>C. dubliniensis<\/jats:italic>\n            -susceptible and -resistant isolates by using probes generated from their homologous\n            <jats:italic>C. albicans<\/jats:italic>\n            sequences. In addition,\n            <jats:italic>ERG11<\/jats:italic>\n            genes were amplified by PCR, and their nucleotide sequences were determined in order to detect point mutations with a possible effect in the affinity for azoles. Decreasing susceptibilities to FLC were detected in\n            <jats:italic>C. dubliniensis<\/jats:italic>\n            isolates recovered from both patients during the course of treatment. FLC-resistant\n            <jats:italic>C. dubliniensis<\/jats:italic>\n            isolates from one patient demonstrated combined upregulation of the\n            <jats:italic>MDR1<\/jats:italic>\n            ,\n            <jats:italic>CDR1<\/jats:italic>\n            , and\n            <jats:italic>ERG11<\/jats:italic>\n            genes. Among the isolates from the second patient, all isolates showing decreased susceptibility to FLC demonstrated upregulation of\n            <jats:italic>MDR1<\/jats:italic>\n            , whereas the levels of mRNA for the\n            <jats:italic>ERG11<\/jats:italic>\n            genes remained constant and the expression of\n            <jats:italic>CDR<\/jats:italic>\n            genes was negligible. Fourteen point mutations were found in the\n            <jats:italic>ERG11<\/jats:italic>\n            genes of the isolates with decreased susceptibility to FLC. These data demonstrate that the development of azole resistance in\n            <jats:italic>C. dublinensis<\/jats:italic>\n            clinical isolates from HIV-infected patients treated with FLC is mediated by multiple molecular mechanisms of resistance, similar to the observations found in the case of\n            <jats:italic>C. albicans<\/jats:italic>\n            .\n          <\/jats:p>","DOI":"10.1128\/aac.46.6.1695-1703.2002","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:09:29Z","timestamp":1027764569000},"page":"1695-1703","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":66,"title":["Molecular Mechanisms of Fluconazole Resistance in\n            <i>Candida dubliniensis<\/i>\n            Isolates from Human Immunodeficiency Virus-Infected Patients with Oropharyngeal Candidiasis"],"prefix":"10.1128","volume":"46","author":[{"given":"Sofia","family":"Perea","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose\u0301 L.","family":"Lo\u0301pez-Ribot","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"Wickes","sequence":"additional","affiliation":[{"name":"Department of Microbiology, The University of Texas Health Science Center at San Antonio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William R.","family":"Kirkpatrick","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga P.","family":"Dib","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano P.","family":"Bachmann","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne M.","family":"Keller","sequence":"additional","affiliation":[{"name":"Department of Microbiology, The University of Texas Health Science Center at San Antonio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas F.","family":"Patterson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases"},{"name":"Audie L. 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