Arsenic inorganic compounds cause oxidative stress mediated by the transcription factor PHO4 in Candida albicans

Verónica Urrialde1, Begoña Alburquerque2, José Pedro Guirao-Abad2

  • 1Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza de Ramón y Cajal s/n, E-28040, Madrid, Spain.

Insights

The transcription factor Pho4 plays a key role in Candida albicans's tolerance to arsenic compounds. Arsenic exposure triggers antioxidant responses in this pathogenic yeast through various mechanisms.

Area of Science:

  • Microbiology
  • Toxicology
  • Molecular Biology

Background:

  • Arsenic is a naturally occurring toxic metalloid.
  • The transcription factor Pho4 is crucial for arsenic compound tolerance in *Candida albicans*.
  • Arsenic compounds, arsenite and arsenate, are environmental toxins.

Purpose of the Study:

  • To analyze the effects of arsenite and arsenate on *Candida albicans*.
  • To investigate the role of the transcription factor Pho4 in the yeast's response to arsenic.
  • To elucidate the mechanisms underlying arsenic tolerance in *C. albicans*.

Main Methods:

  • Analysis of wild-type and *pho4* null mutant *Candida albicans*.
  • Measurement of Reactive Oxygen Species (ROS) production.
  • Assessment of intracellular trehalose accumulation.
  • Enzymatic activity assays for catalase, glutathione reductase, and superoxide dismutase.
  • Evaluation of sensitivity and resistance to arsenic compounds, azide, and related pathways.

Main Results:

  • Both arsenite and arsenate increased ROS production, trehalose accumulation, and catalase activity in wild-type cells.
  • The *pho4* mutant exhibited reduced ROS increase and altered catalase activation kinetics.
  • Glutathione reductase and superoxide dismutase activities were induced solely by arsenite.
  • *pho4* mutant cells showed azide sensitivity and significant arsenate resistance, dependent on the electron transport chain and alternative oxidase.

Conclusions:

  • Arsenic-derived compounds induce a robust antioxidant response in *C. albicans*.
  • Pho4 influences the yeast's reaction to oxidative stress induced by arsenic.
  • Distinct mechanisms mediate the tolerance to arsenite and arsenate, involving oxidative stress pathways and the electron transport system.

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