Dissertations, Theses, and Capstone Projects
Date of Degree
2-2026
Document Type
Doctoral Dissertation
Degree Name
Doctor of Philosophy
Program
Biology
Advisor
Hai-Ping Cheng
Committee Members
Edward Kennelly
Pratyusha Mandal
Stefan Pukatzki
David H Bechhofer
Subject Categories
Biochemistry | Cell Biology | Microbiology
Keywords
Sugar-induced cell death, Yeast, Apoptosis, Antimicrobial, Antimicrobial Resistance, Drug Discovery
Abstract
When Saccharomyces cerevisiae cells are transferred to water alone, they remain viable for many days. However, when transferred to glucose-only solutions, they exhibit a rapid decline in viability. This phenomenon is termed sugar-induced cell death (SICD). Cell death is thought to be triggered by an increase in intracellular reactive oxygen species (ROS) and is associated with a decline in extracellular pH, an increase in plasma membrane potential, and leakage of small molecules. SICD shares similarities with mammalian cell death. When stationary-phase cells are transferred to glucose-only solutions, cell death resembles apoptosis. However, when exponential-phase cells are transferred to glucose-only solutions, cell death resembles primary necrosis. A similar response is observed in mammalian cells exposed to high glucose, particularly in cases of diabetes and hyperglycemia, raising the possibility that this mechanism is conserved in higher eukaryotes.
Since glucose is a universal energy source and signaling molecule for yeast, we propose that glucose does not directly cause cell death but instead signals the production of inhibitory compounds that result in the death of both clonal and neighboring cells. If this hypothesis is supported, these compound(s) could be developed into potential antifungal agents.
We have successfully demonstrated, for the first time, that SICD occurs in a variety of Candida species, including multidrug-resistant (MDR) pathogens: Candida albicans, Candida auris, and Candida glabrata. Additionally, SICD is highly dependent on temperature, occurring mainly at physiological temperature (37 °C). SICD in S. cerevisiae was also found to be highly regulated when induced by low concentrations of glucose and can be prevented either by disrupting apoptotic pathways or by supplementing with essential or non-essential nitrogen sources.
More interestingly, we found that culture supernatants from cells undergoing SICD demonstrate potent antimicrobial activity against clonal cells, MDR Candida spp. (including C. auris), molds, and both Gram-negative and Gram-positive bacteria. Strikingly, SICD culture supernatants induce a cell death phenotype that closely resembles that of cells undergoing SICD, thereby supporting our hypothesis that SICD is caused by the production of inhibitory compound(s).
Our metabolomic analysis suggests that the active compound(s) in the culture supernatants are less than 3 kDa in molecular weight and are hydrophilic, negatively charged, and volatile. We conducted bioassay-guided fractionation to reduce the pool of candidates to 44 metabolites, most of which were unidentified.
Taken together, our data suggest that SICD results in the production of inhibitory compounds with potent antimicrobial activity. Additionally, SICD is highly regulated and occurs primarily at physiological temperature; therefore, this pathway may be of interest not only for the discovery of new antimicrobial agents but also for identifying novel targets in the fight against drug resistance.
Recommended Citation
Parbhudayal, Raveena, "Sugar-Induced Cell Death is a Common Phenomenon in Yeast Mediated by the Production of Broad-Spectrum Antimicrobial Compounds" (2026). CUNY Academic Works.
https://academicworks.cuny.edu/gc_etds/6549
