Yeast Chemogenetic Screening as a Tool to Unravel  the Antifungal Mode of Action of Two Selected Selenocyanates

During recent decades, selenium-containing compounds, as with the chemically similar sulfur-containing compounds, have gained considerable interest as cytotoxic and anticancer agents. Selenocyanates represent a well-established class of organic selenium compounds. These agents exhibit a wide range o...

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Bibliographic Details
Published in:Applied sciences 2019-09, Vol.9 (18), p.3728
Main Authors: Sarfraz, Muhammad, Nasim, Muhammad Jawad, Jacob, Claus, Gruhlke, Martin C.H.
Format: Article
Language:English
Subjects:
Apoptosis
Arabidopsis
Arabidopsis mutants
Cancer
Cell cycle
chemogenetic screening
Chromatography
Cytotoxicity
DNA damage
DNA repair
Fungicides
Genes
glutathione metabolism
Homeostasis
Hypersensitivity
Intracellular levels
Mammals
Metabolism
Metabolites
Mode of action
Mutants
Organoselenium compounds
Oxidants
Oxidative stress
Oxidizing agents
Proteins
Selenium
Selenium compounds
selenocyanates
Sulfur
Yeast
yeast mutants
Yeasts
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Summary:During recent decades, selenium-containing compounds, as with the chemically similar sulfur-containing compounds, have gained considerable interest as cytotoxic and anticancer agents. Selenocyanates represent a well-established class of organic selenium compounds. These agents exhibit a wide range of biological activities. Classically, selenocyanates may cause an increase in the intracellular levels of reactive oxygen species (ROS) and exert cytotoxic activities, thus, acting as pro-oxidants. In this study, chemogenetic profiling was carried out to decipher the resistance mechanisms as central part of the antifungal mode of action against two selected selenocyanates. If a mutant line is less resistant against a compound compared to the wildtype, the gene deleted in that strain seems to be correlated with the resistance. Yeast mutants carrying gene deletions for specific redox-related protein function were employed in the chemogenetic screening. The results of screening reveal the hypersensitivity of mutants carrying deletions for glutathione pool and metabolism. To confirm the results, Arabidopsis mutants deficient in glutathione were subjected to various concentrations of selenocyanates to observe their effects on mutants and the wildtype. A significant dose dependent inhibition in Arabidopsis mutants compared to the wildtype confirmed the findings of the chemogenetic screening. The data suggest that the two representatives of organoselenium compounds cause oxidative stress in yeast cells and glutathione participates towards the development of resistance against the chemicals.
ISSN:2076-3417
2076-3417
DOI:10.3390/app9183728