Mechanisms of Azole Resistance in Clinical Isolates of Candida glabrata Collected during a Hospital Survey of Antifungal Resistance

摘要: The increasing use of azole antifungals for the treatment mucosal and systemic Candida glabrata infections has resulted in selection and/or emergence resistant strains. main mechanisms resistance include alterations C. ERG11 gene (CgERG11), which encodes target enzyme, upregulation CgCDR1 CgCDR2 genes, encode efflux pumps. In present study, we evaluated these molecular 29 unmatched clinical isolates glabrata, 20 were 9 susceptible dose dependent (S-DD) to fluconazole. These recovered from separate patients during a 3-year hospital survey antifungal resistance. Four fluconazole-resistant analyzed together with matched previously taken same patients. Twenty other azole-susceptible included as controls. MIC data all revealed extensive cross-resistance azoles tested, i.e., itraconazole, ketoconazole, voriconazole. Quantitative real-time PCR analyses showed that CgCDR2, alone or combination, upregulated at high levels but two and, lesser extent, fluconazole-S-DD isolates. addition, slight increases relative level expression CgSNQ2 (which an ATP-binding cassette [ABC] transporter not yet been shown be associated resistance) seen some studied. Interestingly, expressing normal exhibited increased CgSNQ2. Conversely, sequencing CgERG11 analysis its no mutation any isolate, suggesting is involved When grown presence fluconazole, profiles including CgERG11, changed only minimally isolates, whereas marked expression, particularly observed either fluconazole-susceptible Finally, known ABC inhibitors, such FK506, able reverse Together, results provide evidence CgCDR1-, CgCDR2-, CgSNQ2-encoded pumps might explain our set