Sugar-induced cell death is temperature dependent and conserved in <i>Saccharomyces cerevisiae</i> and <i>Candida</i> species

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 <i>Saccharomyces cerevisiae</i> undergo SICD. The majority of studies on SICD are focused on <i>S. cerevisiae</i>; 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 <i>S. cerevisiae</i> and <i>Candida</i> spp. We first established that SICD is prevalent in <i>S. cerevisiae</i> and <i>Candida</i> spp.; however, this phenomenon is highly dependent on temperature, which may explain why this phenotype was perhaps missed previously in <i>C. albicans</i>. 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.IMPORTANCESince the discovery of the yeast metacaspase, <i>YCA1</i>, research on cell death and aging in <i>Saccharomyces cerevisiae</i> 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 <i>S. cerevisiae</i>, 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 <i>S. cerevisiae</i>. In this study, we expand the systematic characterization of SICD in <i>Saccharomyces</i> to pathogenic <i>Candida</i> spp. The extension of SICD in pathogenic yeast raises the possibility of this mechanism being of potential interest in therapeutic development.