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Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
Published on: March 19, 2019
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.
Abstract:
Arsenic is a toxic metalloid widespread in nature. Recently, it has been demonstrated a main role of the transcription factor Pho4 in the acquisition of tolerance to arsenic-derived compounds, arsenite and arsenate in Candida albicans. Here, the effect of these compounds on this pathogenic yeast has been analyzed. In wild type cells, both arsenite and arsenate induced a marked increase in the endogenous production of Reactive Oxygen Species (ROS), together with the accumulation of intracellular trehalose and the activation of catalase, suggesting their role as generators of oxidative stress in this yeast. However, a pho4 null mutant showed a minor increase of intracellular ROS and a different kinetics of catalase activation upon exposure to arsenite and arsenate. Interestingly, the enzymatic activity of glutathione reductase and superoxide dismutase were exclusively triggered by arsenite but not by arsenate. pho4 mutant cells were also found to be sensitive to azide but significantly resistant to arsenate through a process dependent on an active electron transport chain and the alternative oxidase system. Therefore, arsenic-derived compounds induce a strong antioxidant response in C.albicans via different mechanisms.
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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