Raveena Parbhudayal, PhD
The Graduate Center of The City University of New York
Sugar-Induced Cell Death in Saccharomyces cerevisiae is Associated with the Production of Broad-Spectrum Antimicrobial Compounds
When Saccharomyces cerevisiae is transferred to water only, they survive for many days. However, when transferred to a glucose-only solution, viability rapidly declines. This phenomenon is called sugar-induced cell death (SICD). SICD can be induced by other carbon sources and can be prevented by neutralizing the extracellular pH or by supplementing with amino acids. The cell death phenotype of cells undergoing SICD resembles that of primary necrosis and apoptosis, depending on the age of the cells. SICD is potentially conserved in eukaryotic cells, as it occurs in other yeast strains and is similar to high-glucose-induced cell death seen in cases of hyperglycemia in mammalian cells. Since glucose is a universal energy source and signaling molecule, we hypothesize that glucose induces the production of a compound that induces cell death.
To test our hypothesis, we collected supernatants from yeast cells incubated in a glucose-only solution and treated other cells. The supernatants inhibited growth and killed producer cells and a range of pathogenic bacteria and yeasts, including Candida albicans, C. glabrata, C. parapsilosis, C. dubliniensis, and C. auris. Glucose in the culture supernatants was depleted, and the cell death phenotype closely resembles that of cells undergoing SICD. These data strongly support the hypothesis that glucose induces the production of the inhibitory compound that results in SICD.
Analysis of the culture supernatant with anti-yeast activity revealed that the activity of the compound is optimal at pH 3.4-4.0, the compound is hydrophilic, negatively charged, and volatile. Therefore, SICD is caused by the production of inhibitory compounds.
When Saccharomyces cerevisiae is transferred to water only, they survive for many days. However, when transferred to a glucose-only solution, viability rapidly declines. This phenomenon is called sugar-induced cell death (SICD). SICD can be induced by other carbon sources and can be prevented by neutralizing the extracellular pH or by supplementing with amino acids. The cell death phenotype of cells undergoing SICD resembles that of primary necrosis and apoptosis, depending on the age of the cells. SICD is potentially conserved in eukaryotic cells, as it occurs in other yeast strains and is similar to high-glucose-induced cell death seen in cases of hyperglycemia in mammalian cells. Since glucose is a universal energy source and signaling molecule, we hypothesize that glucose induces the production of a compound that induces cell death.
To test our hypothesis, we collected supernatants from yeast cells incubated in a glucose-only solution and treated other cells. The supernatants inhibited growth and killed producer cells and a range of pathogenic bacteria and yeasts, including Candida albicans, C. glabrata, C. parapsilosis, C. dubliniensis, and C. auris. Glucose in the culture supernatants was depleted, and the cell death phenotype closely resembles that of cells undergoing SICD. These data strongly support the hypothesis that glucose induces the production of the inhibitory compound that results in SICD.
Analysis of the culture supernatant with anti-yeast activity revealed that the activity of the compound is optimal at pH 3.4-4.0, the compound is hydrophilic, negatively charged, and volatile. Therefore, SICD is caused by the production of inhibitory compounds.
