PERLIN DS, PARK S, MARRAS SA; Interscience Conference on Antimicrobial Agents and Chemotherapy (43rd: 2003: Chicago, Ill.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2003 Sep 14-17; 43: abstract no. M-402.

Public Health Research Institute, Newark, NJ.

BACKGROUND: Triazole resistance in Candida albicans has been a persistent problem for the past decade. Several mechanisms have been linked to triazole resistance, including alteration and/or overexpression of drug target and reduced drug accumulation by overexpression of drug efflux pumps. To quantitatively evaluate the relative contribution of different resistance mechanisms to clinical drug resistance, a diverse collection of clinical isolates were evaluated for mutations within the target gene ERG11, as well as for overexpression of other prominent genes (e.g. drug pumps) associated with azole resistance by real-time quantitative PCR with molecular beacons. METHODS: Fifty-nine strains of Candida albicans that included 14 fluconazole susceptible (MIC <8 microg/ml), 13 susceptible dose dependent (MIC >/= 8-32 microg/ml) and 32 resistant (MIC >/= 64 microg/ml) isolates, as determined by NCCLS M27-A methodology, were used in this study. Isolates were surveyed for overexpression of drug-efflux pumps CDR1, CDR2, FLU1, and MDR1 as well as drug target gene ERG11 by RT-PCR with specific molecular beacon probes. The ERG11 gene was evaluated by DNA sequencing. RESULTS: Overexpression of CDR1, CDR2 and MDR1 was linked to azole resistance phenotypes, although overexpression of MDR1 was more closely associated with resistance. Changes in expression levels for ERG11 and FLU1 were not statistically correlated with resistance. Of twelve total mutations identified in ERG11 for all isolates, only seven mutations were linked to resistance phenotypes. CONCLUSIONS: Multiple mechanisms exist to confer triazole resistance in Candida albicans. However, ERG11 mutations Y132F and S405F were more closely linked to resistance, as was overexpression of MDR1. These targets may represent useful clinical markers for triazole resistance.

Publication Types:

• Meeting Abstracts

Keywords:

• Antigens, Fungal
• Azoles
• Candida albicans
• Fluconazole
• Genes, MDR
• Microbial Sensitivity Tests
• Mutation
• Reverse Transcriptase Polymerase Chain Reaction
• Triazoles
• genetics
• immunology

Other ID:

• GWAIDS0025911

UI: 102265535

From Meeting Abstracts