It has been proposed that sphinganine may function as a natural antifungal barrier in mammals. This sphingoid base is found highly concentrated in epidermis, where it has been documented to inhibit the colonization of pathogenic fungi such as Epidermophyton and Candida. Since Neurospora crassa is sensitive to the effects of sphinganine within the same concentration range as infectious fungi, it is being employed as the model to study the mechanism of sphinganine toxicity in fungal pathogens. With the dramatic increase in fungal mycoses seen in immunocompromised individuals to date, this natural constituent of mammalian epidermis may be employed as a potent, novel antifungal drug.
During this project, radioactive labelling with [3H]sphinganine was employed to observe metabolism of exogenous sphinganine into complex sphingolipids. Transmission electron microscopy analysis was utilized to observe changes in cellular ultrastructure, while fluorescence microscopic techniques were used to assay certain cell functions.
Within 1 hr, exogenous sources of sphinganine are metabolized into dihydroceramides and cerebrosides by the enzymes of complex sphingolipid synthesis.