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

Lin, Ying; Schlievert, Patrick M.; Anderson, Michael; Fair, Christina; Schaefers, Matthew M.; Muthyala, Ramaiah; Peterson, Marnie L.

doi:10.1371/journal.pone.0007499

Cited by 42 publications

(49 citation statements)

References 46 publications

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“…Therefore, other lipids reported to kill S. aureus were tested to determine if these molecules functioned by triggering the leakage of cellular components. 1-Laurylglycerol (12-MG) has antibacterial activity against S. aureus (35,45) and is regarded as a safe food preservative. Because lauric acid (12:0) was a moderately toxic fatty acid (Fig.…”

Section: Resultsmentioning

confidence: 99%

Membrane Disruption by Antimicrobial Fatty Acids Releases Low-Molecular-Weight Proteins from Staphylococcus aureus

et al. 2012

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The skin represents an important barrier for pathogens and is known to produce fatty acids that are toxic toward Gram-positive bacteria. A screen of fatty acids as growth inhibitors of Staphylococcus aureus revealed structure-specific antibacterial activity. Fatty acids like oleate (18:1⌬9) were nontoxic, whereas palmitoleate (16:1⌬9) was a potent growth inhibitor. Cells treated with 16:1⌬9 exhibited rapid membrane depolarization, the disruption of all major branches of macromolecular synthesis, and the release of solutes and low-molecular-weight proteins into the medium. Other cytotoxic lipids, such as glycerol ethers, sphingosine, and acyl-amines blocked growth by the same mechanisms. Nontoxic 18:1⌬9 was used for phospholipid synthesis, whereas toxic 16:1⌬9 was not and required elongation to 18:1⌬11 prior to incorporation. However, blocking fatty acid metabolism using inhibitors to prevent acyl-acyl carrier protein formation or glycerol-phosphate acyltransferase activity did not increase the toxicity of 18:1⌬9, indicating that inefficient metabolism did not play a determinant role in fatty acid toxicity. Nontoxic 18:1⌬9 was as toxic as 16:1⌬9 in a strain lacking wall teichoic acids and led to growth arrest and enhanced release of intracellular contents. Thus, wall teichoic acids contribute to the structure-specific antimicrobial effects of unsaturated fatty acids. The ability of poorly metabolized 16:1 isomers to penetrate the cell wall defenses is a weakness that has been exploited by the innate immune system to combat S. aureus. Staphylococcus aureus is a common cutaneous pathogen responsible for serious infections that are becoming increasingly dangerous due to the prevalence of antibiotic-resistant organisms (8). Lipids have an important role in innate immunity. Human skin deploys a variety of innate defenses against S. aureus colonization that include antimicrobial peptides and fatty acids (9,18,47,49,51). In mice, 16:1⌬9 is the most potent antibacterial fatty acid, whereas humans synthesize a different isomer, 16:1⌬6 (49). It has been known for decades that these skin fatty acids block the growth of S. aureus (21,27,44). Humans (49) and mice (18) deficient in the production of these 16-carbon monounsaturated fatty acids are more susceptible to S. aureus skin infections. However, it is much less clear how these specific fatty acids produce their antibacterial effect. Ideas include the destabilization of the bacterial membrane due to their surfactant properties (19), uncoupling of ATP synthesis (17), the formation of fatty acid hydroperoxides that elicit oxidative stress (29), increased membrane fluidity due to the incorporation in unsaturated fatty acids in phospholipid (5, 7), and the inhibition of de novo fatty acid synthesis at the FabI step (44, 54). These toxic properties of fatty acids stand in contrast to the observations that S. aureus readily incorporates exogenous fatty acids into membrane phospholipids (1, 3, 4, 41) and that acetyl-coenzyme A (CoA) carboxylase knockout mutants can be isolated a...

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Section: Resultsmentioning

confidence: 99%

Membrane Disruption by Antimicrobial Fatty Acids Releases Low-Molecular-Weight Proteins from Staphylococcus aureus

et al. 2012

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“…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.…”

Section: Preventing Superantigen Production By Mucosal Microbicides Amentioning

confidence: 99%

Staphylococcal and Streptococcal Superantigen Exotoxins

et al. 2013

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SUMMARY This review begins with a discussion of the large family of Staphylococcus aureus and beta-hemolytic streptococcal pyrogenic toxin T lymphocyte superantigens from structural and immunobiological perspectives. With this as background, the review then discusses the major known and possible human disease associations with superantigens, including associations with toxic shock syndromes, atopic dermatitis, pneumonia, infective endocarditis, and autoimmune sequelae to streptococcal illnesses. Finally, the review addresses current and possible novel strategies to prevent superantigen production and passive and active immunization strategies.

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“…The production of exotoxins by S. aureus was inhibited at monolaurin concentration that did not inhibit bacterial growth. 14,17,34,35 Monolaurin has 12 carbon molecules in its fatty acid backbone chain, which makes it span exactly one-half the width of a lipid bilayer. 36 Interestingly, it has been reported that the optimum chain length of fatty acids and their corresponding monoglycerides to achieve the maximum antibacterial activity is 12 carbons.…”

Section: Antibacterial Properties Of Ml-lncsmentioning

confidence: 99%

Synergistic interactions between antimicrobial peptides derived from plectasin and lipid nanocapsules containing monolaurin as a cosurfactant against <em>Staphylococcus aureus</em>

Umerska¹,

Cassisa²,

Bastiat³

et al. 2017

IJN

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Development of effective antibacterial agents for the treatment of infections caused by Gram-positive bacteria resistant to existing antibiotics, such as methicillin-resistant Staphylococcus aureus (MRSA), is an area of intensive research. In this work, the antibacterial efficacy of two antimicrobial peptides derived from plectasin, AP114 and AP138, used alone and in combination with monolaurin-lipid nanocapsules (ML-LNCs) was evaluated. Several interesting findings emerged from the present study. First, ML-LNCs and both plectasin derivatives showed potent activity against all 14 tested strains of S. aureus , independent of their resistance phenotype. Both peptides displayed a considerable adsorption (33%–62%) onto ML-LNCs without having an important impact on the particle properties such as size. The combinations of peptide with ML-LNC displayed synergistic effect against S. aureus , as confirmed by two methods: checkerboard and time-kill assays. This synergistic interaction enables a dose reduction and consequently decreases the risk of toxicity and has the potential of minimizing the development of resistance. Together, these results suggest that ML-LNCs loaded with a plectasin derivative may be a very promising drug delivery system for further development as a novel antibacterial agent against S. aureus , including MRSA.

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

Cited by 42 publications

References 46 publications

Membrane Disruption by Antimicrobial Fatty Acids Releases Low-Molecular-Weight Proteins from Staphylococcus aureus

Membrane Disruption by Antimicrobial Fatty Acids Releases Low-Molecular-Weight Proteins from Staphylococcus aureus

Staphylococcal and Streptococcal Superantigen Exotoxins

Synergistic interactions between antimicrobial peptides derived from plectasin and lipid nanocapsules containing monolaurin as a cosurfactant against <em>Staphylococcus aureus</em>

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