Glycerol monolaurate inhibits the effects of Gram-positive select agents on eukaryotic cells

Marnie L Peterson; Patrick M Schlievert

doi:10.1021/bi051992u

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Glycerol monolaurate inhibits the effects of Gram-positive select agents on eukaryotic cells

Journal article

Open access

Peer reviewed

Glycerol monolaurate inhibits the effects of Gram-positive select agents on eukaryotic cells

Marnie L Peterson and Patrick M Schlievert

Biochemistry (Easton), Vol.45(7), pp.2387-2397

02/21/2006

DOI: 10.1021/bi051992u

PMCID: PMC2553893

PMID: 16475828

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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 (>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.

Endothelium, Vascular - cytology

Hemolysis - drug effects

Rabbits

Hemolysin Proteins

Humans

Cells, Cultured

Endothelium, Vascular - drug effects

Shock, Septic - prevention & control

Antigens, Bacterial

Monoglycerides - pharmacology

Superantigens - immunology

Erythrocytes - drug effects

Bacterial Toxins - antagonists & inhibitors

Animals

Inositol 1,4,5-Trisphosphate - secretion

T-Lymphocytes - cytology

Exotoxins - antagonists & inhibitors

T-Lymphocytes - drug effects

Laurates - pharmacology

Details

Title: Subtitle: Glycerol monolaurate inhibits the effects of Gram-positive select agents on eukaryotic cells
Creators: Marnie L Peterson - Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota 55455-0312, USA
Patrick M Schlievert
Resource Type: Journal article
Publication Details: Biochemistry (Easton), Vol.45(7), pp.2387-2397
DOI: 10.1021/bi051992u
PMID: 16475828
PMCID: PMC2553893
NLM abbreviation: Biochemistry
ISSN: 0006-2960
eISSN: 1520-4995
Publisher: United States
Grant note: HL36611 / NHLBI NIH HHS R01 AI074283 / NIAID NIH HHS T32 HD007381 / NICHD NIH HHS R01 AI074283-20 / NIAID NIH HHS AI57164 / NIAID NIH HHS R01 HL036611 / NHLBI NIH HHS T32-HD07381 / NICHD NIH HHS U56 AI057164 / NIAID NIH HHS
Language: English
Date published: 02/21/2006
Academic Unit: Microbiology and Immunology; Internal Medicine
Record Identifier: 9984001211802771

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