Glycerol Monolaurate Inhibits the Effects of Gram-Positive Select Agents on Eukaryotic Cells

Abstract

Many exotoxins of Gram-positive bacteria, such as superantigens [staphylococcal enterotoxins, toxic shock syndrome toxin-1 (TSST-1), and streptococcal pyrogenic exotoxins] and anthrax toxin are bioterrorism agents that cause diseases by immunostimulation or cytotoxicity. Glycerol monolaurate (GML), a fatty acid monoester found naturally in humans, has been reported to prevent synthesis of Gram-positive bacterial exotoxins. This study explored the ability of GML to inhibit the effects of exotoxins on mammalian cells and prevent rabbit lethality from TSS. GML (≥10 μg/mL) inhibited superantigen (5 μg/mL) immunoproliferation, as determined by inhibition of ³H-thymidine incorporation into DNA of human peripheral blood mononuclear cells (1 × 10⁶ cells/mL) as well as phospholipase Cγ1, suggesting inhibition of signal transduction. The compound (20 μg/mL) prevented superantigen (100 μg/mL) induced cytokine secretion by human vaginal epithelial cells (HVECs) as measured by ELISA. GML (250 μg) inhibited rabbit lethality as a result of TSST-1 administered vaginally. GML (10 μg/mL) inhibited HVEC and macrophage cytotoxicity by anthrax toxin, prevented erythrocyte lysis by purified hemolysins (staphylococcal α and β) and culture fluids containing streptococcal and Bacillus anthracis hemolysins, and was nontoxic to mammalian cells (up to 100 μg/mL) and rabbits (250 μg). GML stabilized mammalian cell membranes, because erythrocyte lysis was reduced in the presence of hypotonic aqueous solutions (0−0.05 M saline) or staphylococcal α- and β-hemolysins when erythrocytes were pretreated with GML. GML may be useful in the management of Gram-positive exotoxin illnesses; its action appears to be membrane stabilization with inhibition of signal transduction.