Antimicrobial activity of sphingosines

Abstract

The antimicrobial activity of stratum corneum lipids was examined by screening in vitro various representative phospholipids and sphingolipids. Of mixed galacto-cerebrosides; phosphatidic acid; phosphatidic acid-monomethylester-dioleoyl; phosphatidylethanolamine; phosphatidylethanolamine-beta-oleoyl-gamma-palmitoyl; phosphatidylcholine; D-sphingosine; D,L-sphinganine; 4-D-hydroxysphinganine; oleoyl-sphingosine; N,N-dimethylsphingosine; and stearylamine, only the sphingosines and, to a lesser extent, stearylamine were clearly and profoundly effective against Staphylococcus aureus (4-log reduction at 6.25 micrograms/ml [20 microM]; 2-log reduction at 0.78 mu/ml [2.5 microM]). The sphingosines were similarly active against Streptococcus pyogenes, Micrococcus luteus, Propionibacterium acnes, Brevibacterium epidermidis, and Candida albicans, moderately active against Pseudomonas aeruginosa, and ineffective against Escherichia coli and Serratia marcescens. Both erythro- and threo-isomers were effective. Optimal inhibition was at 60 min incubation at 37 degrees C and at pH 6.5. Antimicrobial activity, which was Ca++ dependent, was confirmed in vivo by topical application and microbial challenge. Because free sphingosines are available in the stratum corneum and other epidermal layers, these lipids may contribute to the cutaneous antimicrobial barrier.