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.

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.

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