Association of ADH1 and DDR48 Expression with Azole Resistance in Candida Albicans
Objectives: The ADH1 (alcohol dehydrogenase) and DDR48 genes were found to be upregulated in fluconazole resistant Candida albicans. Understanding the drug resistance mechanisms and genes will help in the development of new antifungal agents that can reverse drug resistance. This study aimed to investigate the role of ADH1and DDR48 genes in fluconazole resistance in C. albicans.
Methods: This study involved 19 fluconazole susceptible and 6 fluconazole resistant C. albicans isolates. The MICs of fluconazole were determined by the E-test. Quantitative expressions of ADH1, CDR1 (Candida Drug Resistance), DDR48 and FLU1 genes were assessed by real time PCR.
Results: There was a statistically significant higher expression levels of CDR1, FLU1, ADH1 and DDR48 in resistant and susceptible dose dependent isolates than in susceptible isolates (P = 0.009, 0.008, 0.01, 0.014 respectively). Strong positive correlations were observed between the expression levels of each of ADH1and DDR4 with azole resistance genes CDR1 and FLU1 [(rs) = 0.945, 0.815, respectively; P <0.001; (rs) = 0.852 and 0.76, respectively; P <0.001].
Conclusions: This is the first study that showed positive correlation between DDR48 and azole resistance genes. It indicated that ADH1 and DDR48 are associated with the resistance mechanisms of C. albicans to fluconazole. Identification of new drugs that target the proteins encoded by these genes will help in eradication of fluconazole resistant C. albicans.
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