Overexpression as a major genetic mechanism of fluconazole resistance in Candida albicans isolated from HIV patients in Indonesia

Global Medical Microbiology Summit & Expo

November 28-29, 2016 San Francisco, USA

Yeva Rosana

Universitas Indonesia, Indonesia

Posters & Accepted Abstracts: J Med Microb Diagn

Abstract :

Overexpression and mutations as a genetic mechanism of Candida albicans resistance to fluconazole have been reported. Mechanisms responsible for Candida albicans isolated from HIV patients in Indonesia are less understood. Overused of fluconazole for treatment of oropharyngeal candidiasis, which was the third most common opportunistic infection in HIV/AIDS patients in Indonesia could lead to the emergence of resistance. Result analysis of ERG11, CDR1, CDR2 and MDR1 by real-time RT-PCR and ERG11 gene mutation using sequencing methods showed that the highest gene overexpression of CDR2 was detected in all isolates of C. albicans resistant to multiple azoles, overexpression of ERG11 gene that play a role in C. albicans isolates resistant to a single fluconazole. Although amino acid substitutions were observed at six positions, i.e. D116E, D153E, I261V, E266D, V437I and V488I, it seems not directly related to the fluconazole resistance. This shows that the genetic polymorphism lanosterol 14-�± demethylase is highly permissive to structural changes. Amino acid substitution at I261V due to ERG11 genes mutation identified in this study is probably associated with fluconazole resistance, since it is located at the �² helical chain, the binding site of fluconazole and the substitution from the large size isoleucine amino acid to small size valine hinders the entry of fluconazole. 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.

Biography :

Email: yeva.rosana@ui.ac.id