Modulation of antioxidant defence system in response to berberine in Candida albicans

Yeast. 2021 Feb;38(2):157-169. doi: 10.1002/yea.3531. Epub 2020 Dec 10.

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.

Keywords: Candida albicans; antioxidant enzymes; berberine; gene expression; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Berberine / pharmacology*
  • Candida albicans / drug effects*
  • Candida albicans / genetics*
  • Drug Resistance, Fungal
  • Fungal Proteins / genetics
  • Microbial Sensitivity Tests
  • Reactive Oxygen Species / metabolism
  • Up-Regulation

Substances

  • Antifungal Agents
  • Antioxidants
  • Fungal Proteins
  • Reactive Oxygen Species
  • Berberine