Overexpression and mutation as a genetic mechanism of fluconazole resistance in Candida albicans isolated from human immunodeficiency virus patients in Indonesia

• DOI: 10.1099/jmm.0.000123
• Publication Date: 2015-07-09T23:12:10Z
• Authors: Yeva Rosana; Andi Yasmon; Delly Chipta Lestari
• Keywords: 0301 basic medicine; Antifungal Agents; Molecular Sequence Data; Candidiasis; HIV Infections; Gene Expression Regulation, Enzymologic; 3. Good health; Fungal Proteins; Sterol 14-Demethylase; 03 medical and health sciences; Drug Resistance, Fungal; Indonesia; Gene Expression Regulation, Fungal; Candida albicans; Humans; Fluconazole

Fluconazole is the standard treatment for oropharyngeal candidiasis, which is the third most common opportunistic infection in human immunodeficiency virus (HIV)/AIDS patients in Indonesia. Overuse of this drug could lead to the emergence of resistance. The objective of this study was to analyse the role of ERG11, CDR1, CDR2 and MDR1 gene overexpression and mutations in the ERG11 gene as a genetic mechanism of fluconazole resistance in Candida albicans isolated from HIV patients in Indonesia. Overexpression of ERG11, CDR1, CDR2 and MDR1 was analysed by real-time reverse transcription PCR, while ERG11 gene mutation analysis was performed using sequencing methods. Seventeen isolates out of 92 strains of C. albicans isolated from 108 HIV patients were found to be resistant to azole antifungals. The highest gene overexpression of ERG11 was found in C. albicans resistant to single fluconazole, while the highest gene overexpression of CDR2 was detected in all isolates of C. albicans resistant to multiple azoles. Amino acid substitutions were observed at six positions, i.e. D116E, D153E, I261V, E266D, V437I and V488I. The amino acid substitution I261V was identified in this study and was probably associated with fluconazole resistance. The combination of overexpression of CDR2 and ERG11 and mutation in the ERG11 gene was found to be a genetic mechanism of fluconazole resistance in C. albicans isolated from HIV patients in Indonesia.