Sugar-induced cell death is temperature dependent and conserved in Saccharomyces cerevisiae and Candida species

ABSTRACT Yeast sugar-induced cell death (SICD) is a phenomenon whereby cells lose viability in the presence of glucose and the absence of other nutrients to support their growth. Both stationary- and exponential-phase cells of Saccharomyces cerevisiae undergo SICD. The majority of studies on SICD are focused on S. cerevisiae ; however, since glucose is a universal carbon source for yeast, we hypothesized that a similar response may be seen in other species of yeast. In this study, we sought to conduct a comparative analysis of SICD in S. cerevisiae and Candida spp. We first established that SICD is prevalent in S. cerevisiae and Candida spp.; however, this phenomenon is highly dependent on temperature, which may explain why this phenotype was perhaps missed previously in C. albicans . We found that glucose is a universal inducer of cell death in all tested strains, but other carbon sources may also lead to cell death to a lesser extent. Additionally, cells transferred to a glucose-only solution induce a dramatic decline in extracellular pH, which may not be directly associated with cell death. Together, our data suggest that SICD is a fundamental and conserved mechanism in yeast. IMPORTANCE Since the discovery of the yeast metacaspase, YCA1 , research on cell death and aging in Saccharomyces cerevisiae has expanded significantly. Increasing evidence demonstrates similarities between yeast and mammalian cell death. A less discussed type of cell death is sugar-induced cell death (SICD). SICD is a phenomenon observed in S. cerevisiae , whereby cells transferred to water-only remain viable for many days; however, when transferred to glucose-only solutions, there is a rapid loss of viability. Studies on SICD in yeast have been focusing mostly on S. cerevisiae . In this study, we expand the systematic characterization of SICD in Saccharomyces to pathogenic Candida spp. The extension of SICD in pathogenic yeast raises the possibility of this mechanism being of potential interest in therapeutic development.