Modulation of antioxidant defense system in response to berberine in Candida albicans.

Emergence of multidrug resistant species of Candida is evolving, which advocates an urgent need for the development of new therapeutic strategies and antifungal drugs. Activation of antioxidant defense system in Candida albicans is known as forefront mechanism to escape drug toxicity. This study evaluated the role of antioxidant defense genes in the susceptibility to fluconazole in C. albicans. And also determined the effect of berberine on growth, antioxidant enzymes and the expression of their genes in C. albicans isolates. Expression of major antioxidant genes was significantly increased in fluconazole resistant isolates in comparison to the susceptible group. Antifungal susceptibility against berberine showed MIC values ranging from 125 to 500 μg/ml. Berberine treatment caused upregulation of mRNA expression and enzymatic activities of the targeted major antioxidants. Interestingly, C. albicans exhibited efficient antioxidant response at lower concentrations but could not sufficiently alleviate berberine-induced oxidative stress occurring at concentrations above 250 μg/ml. Therefore, berberine could serve as a potent ROS-inducing agent, disrupting the antioxidant system especially in fluconazole resistant C. albicans to overcome antifungal drug resistance.