Glycerol monolaurate inhibits the effects of Gram-positive select agents on eukaryotic cells.
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 (>or=10 microg/mL) inhibited superantigen (5 microg/mL) immunoproliferation, as determined by inhibition of (3)H-thymidine incorporation into DNA of human peripheral blood mononuclear cells (1 x 10(6) cells/mL) as well as phospholipase Cgamma1, suggesting inhibition of signal transduction. The compound (20 microg/mL) prevented superantigen (100 microg/mL) induced cytokine secretion by human vaginal epithelial cells (HVECs) as measured by ELISA. GML (250 microg) inhibited rabbit lethality as a result of TSST-1 administered vaginally. GML (10 microg/mL) inhibited HVEC and macrophage cytotoxicity by anthrax toxin, prevented erythrocyte lysis by purified hemolysins (staphylococcal alpha and beta) and culture fluids containing streptococcal and Bacillus anthracis hemolysins, and was nontoxic to mammalian cells (up to 100 microg/mL) and rabbits (250 microg). GML stabilized mammalian cell membranes, because erythrocyte lysis was reduced in the presence of hypotonic aqueous solutions (0-0.05 M saline) or staphylococcal alpha- and beta-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.
Peterson
Marnie L
ML
Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota 55455-0312, USA.
Schlievert
Patrick M
PM
D000818:Animals; D000942:Antigens, Bacterial; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects; D005098:Exotoxins / Q000037:antagonists & inhibitors*; D006460:Hemolysin Proteins; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007848:Laurates / Q000494:pharmacology*; D050178:Monoglycerides / Q000494:pharmacology*; D011817:Rabbits; D012772:Shock, Septic / Q000517:prevention & control; D018089:Superantigens / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D005098:Exotoxins; D006460:Hemolysin Proteins; D007848:Laurates; D050178:Monoglycerides; D018089:Superantigens; C030325:anthrax toxin; C021091:staphylococcal alpha-toxin; C020777:monolaurin; D015544:Inositol 1,4,5-Trisphosphate