CHOLESTEROL SULFATE PROTECTS CANDIDA-ALBICANS FROM INHIBITION BY SPHINGOSINE IN-VITRO

Sphingosine is known to have potent biological activity, including pro nounced anti-microbial action in vitro against Candida albicans and so me bacteria, Several sphingosine bases are present in stratum corneum at concentrations several orders of magnitude above those in other tis sues, Sphingosine forms an undissociated salt with organic sulfates, h owever, so that the free sphingosine in the epidermis may be inactivat ed by the cholesterol sulfate known to be present, To investigate this hypothesis, C, albicans was grown in cultures with graded concentrati ons of sphingosine added in ethanol, In 1% ethanol, 0.1-100 mu g/ml sp hingosine completely prevented growth of the organism for 12 h. All cu ltures eventually entered log-phase growth and reached limiting densit y at a rate inversely proportional to sphingosine concentration. When sphingosine was added, together with an equimolar amount of cholestero l sulfate, there was no delay in the onset. of growth of the yeast and the rate of growth and final density were similar to control cultures , These results demonstrate that natural ratios of cholesterol sulfate neutralize the antimicrobial activity of sphingosine in vitro, In the epidermis, endogenous cholesterol sulfate is hydrolyzed by sterol sul fatase at the skin surface, where the released sphingosine may resist microbial colonization of the stratum corneum. This mechanism for libe rating anti-microbial sphingosine base only at the skin surface may pr otect the viable epidermis against known cytotoxic effects of free sph ingosine.