{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:40:01Z","timestamp":1791232801066,"version":"4.1.0"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2005,2,1]],"date-time":"2005-02-01T00:00:00Z","timestamp":1107216000000},"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":[[2005,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The increasing use of azole antifungals for the treatment of mucosal and systemic\n            <jats:italic>Candida glabrata<\/jats:italic>\n            infections has resulted in the selection and\/or emergence of resistant strains. The main mechanisms of azole resistance include alterations in the\n            <jats:italic>C. glabrata ERG11<\/jats:italic>\n            gene (\n            <jats:italic>CgERG11<\/jats:italic>\n            ), which encodes the azole target enzyme, and upregulation of the\n            <jats:italic>CgCDR1<\/jats:italic>\n            and\n            <jats:italic>CgCDR2<\/jats:italic>\n            genes, which encode efflux pumps. In the present study, we evaluated these molecular mechanisms in 29 unmatched clinical isolates of\n            <jats:italic>C. glabrata<\/jats:italic>\n            , of which 20 isolates were resistant and 9 were susceptible dose dependent (S-DD) to fluconazole. These isolates were recovered from separate patients during a 3-year hospital survey for antifungal resistance. Four of the 20 fluconazole-resistant isolates were analyzed together with matched susceptible isolates previously taken from the same patients. Twenty other azole-susceptible clinical\n            <jats:italic>C. glabrata<\/jats:italic>\n            isolates were included as controls. MIC data for all the fluconazole-resistant isolates revealed extensive cross-resistance to the other azoles tested, i.e., itraconazole, ketoconazole, and voriconazole. Quantitative real-time PCR analyses showed that\n            <jats:italic>CgCDR1<\/jats:italic>\n            and\n            <jats:italic>CgCDR2<\/jats:italic>\n            , alone or in combination, were upregulated at high levels in all but two fluconazole-resistant isolates and, to a lesser extent, in the fluconazole-S-DD isolates. In addition, slight increases in the relative level of expression of\n            <jats:italic>CgSNQ2<\/jats:italic>\n            (which encodes an ATP-binding cassette [ABC] transporter and which has not yet been shown to be associated with azole resistance) were seen in some of the 29 isolates studied. Interestingly, the two fluconazole-resistant isolates expressing normal levels of\n            <jats:italic>CgCDR1<\/jats:italic>\n            and\n            <jats:italic>CgCDR2<\/jats:italic>\n            exhibited increased levels of expression of\n            <jats:italic>CgSNQ2<\/jats:italic>\n            . Conversely, sequencing of\n            <jats:italic>CgERG11<\/jats:italic>\n            and analysis of its expression showed no mutation or upregulation in any\n            <jats:italic>C. glabrata<\/jats:italic>\n            isolate, suggesting that\n            <jats:italic>CgERG11<\/jats:italic>\n            is not involved in azole resistance. When the isolates were grown in the presence of fluconazole, the profiles of expression of all genes, including\n            <jats:italic>CgERG11<\/jats:italic>\n            , were not changed or were only minimally changed in the resistant isolates, whereas marked increases in the levels of gene expression, particularly for\n            <jats:italic>CgCDR1<\/jats:italic>\n            and\n            <jats:italic>CgCDR2<\/jats:italic>\n            , were observed in either the fluconazole-susceptible or the fluconazole-S-DD isolates. Finally, known ABC transporter inhibitors, such as FK506, were able to reverse the azole resistance of all the isolates. Together, these results provide evidence that the upregulation of the\n            <jats:italic>CgCDR1<\/jats:italic>\n            -,\n            <jats:italic>CgCDR2<\/jats:italic>\n            -, and\n            <jats:italic>CgSNQ2<\/jats:italic>\n            -encoded efflux pumps might explain the azole resistance in our set of isolates.\n          <\/jats:p>","DOI":"10.1128\/aac.49.2.668-679.2005","type":"journal-article","created":{"date-parts":[[2005,1,26]],"date-time":"2005-01-26T22:04:40Z","timestamp":1106777080000},"page":"668-679","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":274,"title":["Mechanisms of Azole Resistance in Clinical Isolates of\n            <i>Candida glabrata<\/i>\n            Collected during a Hospital Survey of Antifungal Resistance"],"prefix":"10.1128","volume":"49","author":[{"given":"Maurizio","family":"Sanguinetti","sequence":"first","affiliation":[{"name":"Istituto di Microbiologia, Universita\u0300 Cattolica del Sacro Cuore, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brunella","family":"Posteraro","sequence":"additional","affiliation":[{"name":"Istituto di Microbiologia, Universita\u0300 Cattolica del Sacro Cuore, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Fiori","sequence":"additional","affiliation":[{"name":"Istituto di Microbiologia, Universita\u0300 Cattolica del Sacro Cuore, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Ranno","sequence":"additional","affiliation":[{"name":"Istituto di Microbiologia, Universita\u0300 Cattolica del Sacro Cuore, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Torelli","sequence":"additional","affiliation":[{"name":"Istituto di Microbiologia, Universita\u0300 Cattolica del Sacro Cuore, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Fadda","sequence":"additional","affiliation":[{"name":"Istituto di Microbiologia, Universita\u0300 Cattolica del Sacro Cuore, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/513663"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0732-8893(01)00214-0"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1007\/s100960050255","volume":"18","year":"1999","unstructured":"Barchiesi, F., L. 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