Investigation of mutations in Erg11 gene of fluconazole resistant Candida albicans isolates from Turkish hospitals

• Published in: Mycoses Vol. 54; no. 2; pp. 99 - 104
• Main Authors: Manastır, Lerzan, Ergon, M. Cem, Yücesoy, Mine
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-03-2011
• Subjects: Antifungal Agents - pharmacology; azoles; Candida albicans; Candida albicans - drug effects; Candida albicans - enzymology; Candida albicans - genetics; Candida albicans - isolation & purification; Drug Resistance, Fungal; Enzymes; ERG11 gene; ERG3 gene; fluconazole; Fluconazole - pharmacology; Fungal Proteins - genetics; Fungal Proteins - metabolism; Hospitals; Humans; Molecular Sequence Data; Mutation; mutations; Nucleotides; resistance
• ISSN: 0933-7407; 1439-0507
• DOI: 10.1111/j.1439-0507.2009.01766.x

Widespread use of fluconazole has resulted in resistance in strains of Candida. The aim of our study was to investigate Y132H and other mutations in the ERG11 gene in conferring fluconazole resistance to C. albicans isolates. Seven fluconazole-resistant (R)/susceptible dose-dependent (SDD)/trailing and 10 fluconazole-susceptible (S) isolates were included. Restriction enzyme analysis was performed on all isolates for Y132H mutation and sequence analysis was performed for other mutations in the ERG11 gene. None of our strains had Y132H mutation. One single mutation (D153E, E266D, D116E, V437I) was detected in isolates 348, 533, 644, 1453, 2157, while the others had more than one nucleotide change. D116E and E266D, which were two mutations found in fluconazole R/SDD/trailing isolates with the highest frequency, were also detected in azole S strains. K143R, G464S, G465S and V488I mutations were determined in three of the R/SDD isolates. S412T and R469K mutations were detected only in this group of strains by sequence analysis. Mutations such as K143R, G464S, G465S, V488I, S412T and R469K in the ERG11 gene were determined to be effective mechanisms in our fluconazole R/SDD C. albicans isolates. Other mechanisms of resistance, such as overexpression of ERG11 and efflux pumps and mutations in the ERG3 gene should also be investigated.