Surfactants, Aromatic and Isoprenoid Compounds, and Fatty Acid Biosynthesis Inhibitors Suppress Staphylococcus aureus Production of Toxic Shock Syndrome Toxin 1

Abstract

Menstrual toxic shock syndrome is a rare but potentially life-threatening illness manifest through the actions of Staphylococcus aureus toxic shock syndrome toxin 1 (TSST-1). Previous studies have shown that tampon additives can influence staphylococcal TSST-1 production. We report here on the TSST-1-suppressing activity of 34 compounds that are commonly used additives in the pharmaceutical, food, and perfume industries. Many of the tested chemicals had a minimal impact on the growth of S. aureus and yet were potent inhibitors of TSST-1 production. The TSST-1-reducing compounds included surfactants with an ether, amide, or amine linkage to their fatty acid moiety (e.g., myreth-3-myristate, Laureth-3, disodium lauroamphodiacetate, disodium lauramido monoethanolamido, sodium lauriminodipropionic acid, and triethanolamine laureth sulfate); aromatic compounds (e.g. phenylethyl and benzyl alcohols); and several isoprenoids and related compounds (e.g., terpineol and menthol). The membrane-targeting and -altering effects of the TSST-1-suppressing compounds led us to assess the activity of molecules that are known to inhibit fatty acid biosynthesis (e.g., cerulenin, triclosan, and hexachlorophene). These compounds also reduced S. aureus TSST-1 production. This study suggests that more additives than previously recognized inhibit the production of TSST-1.

Glycerol Monolaurate and Dodecylglycerol Effects on Staphylococcus aureus and Toxic Shock Syndrome Toxin-1 In Vitro and In Vivo

“…In our study, GML (25–50 µg/ml) was able to inhibit TSST-1 production independent of S. aureus growth inhibition properties, which is in agreement with previously described results by Schlievert et al (20 µg/ml) [15], and Holland et al (17 µg/ml) [31]. DDG was also reported to inhibit TSST-1 production by McNamara and colleagues [20]. However, our results suggest that DDG, and likely other glycerol monoethers, inhibition of toxin production is dependent on bacterial growth inhibition, which is different from that of GML.…”

“…Many surfactants, including fatty acids linked through ester, ether, amide, or amine bonds, appear to inhibit S. aureus growth and toxin production [20]. However, fatty acid esters and amides are susceptible to S. aureus enzyme degradation, and amines are irritable to mucous membranes [29].…”

Staphylococcal and Streptococcal Superantigen Exotoxins

“…optiBalance tampons in Europe. Other molecules that could be applied to mucosal surfaces and devices to reduce the risk of staphylococcal and streptococcal illnesses have also been identified (306)(307)(308)(309), including agents that prevent superantigen production and those that stabilize mucosal surfaces.…”

Crystal structure and fluorescence studies reveal the role of helical dimeric interface of staphylococcal fabg1 in positive cooperativity for NADPH

“…This unambiguously indicates the importance of the fatty acid synthesis in this Gram‐positive coccus. The sole source of fatty acid in staphylococcus is governed by the type II fatty acid synthesis pathway and thus the understanding the FASII is in demand to combat the Staphylococcal infection 4. More recently, the essentiality of type II fatty acid synthesis (FAS‐II) has been validated for S. aureus.…”