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Induction of Apoptosis in Candida albicans by Sphinganine

M. L. St. Louis, A. Cortese, L. R. Aaronson

 

Sphinganine is a simple sphingolipid that is a precursor in the synthesis of complex sphingolipids such as cerebrosides, ceramides and sphingomyelin. Free sphingoid bases have been found in epidermal tissue at concentrations as high as 250 µM where they have been shown to exhibit potent antifungal activity. Research in our lab has demonstrated that among other affects, sublethal concentrations of sphinganine (<12.5 µM) inhibited the yeast-to-hyphal morphological transition in the dimorphic fungus, Candida albicans. At concentrations of 12.5 µM and higher, viability of C. albicans cells declined sharply. Recent reports have shown that sphingoid bases such as sphinganine induce apoptosis-like events in the filamentous fungi Neurospora crassa and Aspergilus nidulans. Apoptosis in these fungi is a complex process of programmed cell death caused by environmental stress, which can result in fragmentation of chromatin within a cell. However, the induction of apoptosis by sphinganine in dermatophytic fungal species such as C. albicans has been undetermined. Since growth and viability of C. albicans are impaired by incubation with sphinganine, we hypothesized that C. albicans yeast-phase cells exposed to sphinganine would exhibit apoptotic fragmentation of chromatin. Neurospora crassa was used as a control for comparison of chromatin fragmentation as a result of apoptosis. Using a terminal deoxynucleotidyl fluorescein-dUTP nick-end labeling (TUNEL) assay, we observed evidence of chromatin fragmentation in C. albicans yeast cells at concentrations of sphinganine as low as 12.5 µM after 4 hrs of incubation, similar to that observed in N. crassa. The concentration dependence of this phenomenon is consistent with the sphinganine dose-response curve for loss of cell viability. Results indicate that although C. albicans is a significantly different fungus than previously studied molds, it is similarly susceptible to sphinganine-induced apoptosis.