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Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
Published on: March 19, 2019
Modulation of antioxidant defence system in response to berberine in Candida albicans
Evida Poopedi1, Musa Marimani2, Suliman Yousef AlOmar3
1Clinical Microbiology and Infectious Diseases, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa.
Abstract:
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 defence system in Candida albicans is known as forefront mechanism to escape drug toxicity. This study evaluated the role of antioxidant defence 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 with 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 greater than 250 μg/ml. Therefore, berberine could serve as a potent Reactive Oxygen Species (ROS)-inducing agent, disrupting the antioxidant system especially in fluconazole-resistant C. albicans to overcome antifungal drug resistance. TAKE AWAYS: Evaluated the role of antioxidant enzymes in FLC resistance in C. albicans Studied the effect of berberine on growth of different C. albicans isolates Investigated the modulation of antioxidant enzymes by berberine in C. albicans Studied the effect of berberine on antioxidant gene expression in C. albicans.
Insights
Multidrug-resistant Candida albicans employs antioxidant defenses to resist fluconazole. Berberine disrupts this system by inducing oxidative stress, offering a potential strategy to overcome antifungal resistance.
Area of Science:
- Mycology
- Antimicrobial Resistance
- Biochemistry
Background:
- Multidrug resistance in Candida species, particularly Candida albicans, is a growing clinical concern.
- The antioxidant defense system in Candida albicans is a key mechanism for surviving antifungal drug toxicity.
- Fluconazole resistance is often associated with the upregulation of antioxidant genes.
Purpose of the Study:
- To investigate the role of antioxidant defense genes in fluconazole resistance in Candida albicans.
- To evaluate the effect of berberine on the growth, antioxidant enzyme activity, and gene expression in Candida albicans isolates.
- To determine if berberine can overcome fluconazole resistance by disrupting the antioxidant system.
Main Methods:
- Comparative analysis of antioxidant gene expression in fluconazole-susceptible and resistant Candida albicans isolates.
- Determination of minimum inhibitory concentrations (MICs) for berberine against Candida albicans.
- Measurement of antioxidant enzyme activities and mRNA expression levels following berberine treatment.
Main Results:
- Fluconazole-resistant isolates showed significantly higher expression of major antioxidant genes compared to susceptible isolates.
- Berberine exhibited antifungal activity with MIC values ranging from 125 to 500 μg/ml.
- Berberine treatment upregulated both the expression and enzymatic activity of key antioxidant enzymes in Candida albicans.
- Candida albicans could not overcome berberine-induced oxidative stress at concentrations above 250 μg/ml.
Conclusions:
- Berberine effectively disrupts the antioxidant system in Candida albicans, particularly in fluconazole-resistant strains.
- Berberine acts as a potent inducer of Reactive Oxygen Species (ROS), overwhelming the fungal antioxidant defenses.
- Berberine shows promise as a therapeutic agent to combat fluconazole-resistant Candida albicans infections by overcoming drug resistance.

