Overexpression and Mutation as a Genetic Mechanism of Fluconazole Resistance in Candida albicans Isolated from HIV Patients in Indonesia.
J Med Microbiol. 2015 Jul 9;
Authors: Rosana Y, Yasmon A, Lestari DC
Fluconazole was the standard treatment for oropharyngeal candidiasis, which was the third most common opportunistic infection in HIV/AIDS patients in Indonesia. Overused of this drug could lead to the emergence of resistance. The objective of this study was to analyze 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 analyzed by real-time RT-PCR, while ERG11 gene mutation analysis was performed using sequencing methods. Twelve isolates out of 92 strains of C. albicans isolated from 108 HIV patients were found to be resistant to fluconazole antifungals. The highest gene overexpression of ERG11 was found in C. albicans resistance 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. An amino acid substitution at I261V was identified in this study and was probably associated with fluconazole resistance. However, the combination of overexpression of CDR2 and ERG11 and mutation in the ERG11 gene were responsible as a genetic mechanism of fluconazole resistance in C. albicans isolated from HIV patients in Indonesia.
PMID: 26297039 [PubMed - as supplied by publisher]