Glycerol monolaurate inhibits the production of beta-lactamase, toxic shock toxin-1, and other staphylococcal exoproteins by interfering with signal transduction

Projan, Steven J.; Brown-Skrobot, Susan; Schlievert, Patrick M.; Vandenesch, F.; Novick, Richard P.

doi:10.1128/jb.176.14.4204-4209.1994

Cited by 143 publications

(145 citation statements)

References 28 publications

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“…The gene for PSM-mec was identified in MRSA strains carrying the staphylococcal cassette chromosome mec (SCCmec) types II or III. The expression of all psm genes is controlled by the Agr system for quorum sensing (8,(11)(12)(13). This system modulates gene expression such that cell wall-associated virulence factors (e.g., the immunoglobulin G-binding protein A) are most highly expressed at low cell densities and that secreted virulence factors (e.g., the PSMs) are most highly expressed at high cell densities (14-21).…”

Section: S Taphylococcus Aureus Is An Opportunistic Human Pathogen Thatmentioning

confidence: 99%

Distinct Roles of Phenol-Soluble Modulins in Spreading of Staphylococcus aureus on Wet Surfaces

Tsompanidou

Denham

Becher

et al. 2013

Appl Environ Microbiol

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The human pathogen Staphylococcus aureus is renowned for the rapid colonization of contaminated wounds, medical implants, and food products. Nevertheless, little is known about the mechanisms that allow S. aureus to colonize the respective wet surfaces. The present studies were therefore aimed at identifying factors used by S. aureus cells to spread over wet surfaces, starting either from planktonic or biofilm-associated states. Through proteomics analyses we pinpoint phenol-soluble modulins (PSMs) as prime facilitators of the spreading process. To dissect the roles of the eight PSMs produced by S. aureus, these peptides were chemically synthesized and tested in spreading assays with different psm mutant strains. The results show that PSM␣3 and PSM␥ are the strongest facilitators of spreading both for planktonic cells and cells in catheter-associated biofilms. Compared to the six other PSMs of S. aureus, PSM␣3 and PSM␥ combine strong surfactant activities with a relatively low overall hydropathicity. Importantly, we show that PSM-mediated motility of S. aureus facilitates the rapid colonization of wet surfaces next to catheters and the colonization of fresh meat. S taphylococcus aureus is an opportunistic human pathogen thatcan cause a wide range of acute and chronic diseases, which range from superficial skin infections to life-threatening endocarditis and sepsis (1, 2). The ability of this Gram-positive bacterium to cause these infections depends on the production of secreted and cell wall-associated virulence factors. Of increasing concern is the ability of S. aureus to acquire resistance against antibiotics, as underscored by the global spread of methicillin-resistant S. aureus (MRSA) lineages.Intriguingly, recent proteomics studies have revealed an enormous diversity in the production of virulence factors by different isolates of S. aureus, and only a few of these seem to be invariantly produced (3-5). Among the most commonly identified staphylococcal virulence factors, especially in the community-associated (CA)-MRSA lineages, are the so-called phenol-soluble modulins (PSMs) (6). These PSMs are short, amphipathic, ␣-helical peptides that have leukocidal activity and biosurfactant properties (7-9). The growth media of S. aureus cultures contain both N-terminally formylated and deformylated PSMs, suggesting that these virulence factors are substrates for the bacterial N-formylmethionine deformylase (9, 10).To date, eight PSMs have been identified in S. aureus. These include the four PSM␣1 to PSM␣4 peptides (22 residues each), the PSM␤1 and PSM␤2 peptides (44 residues each), PSM␥ (25 residues) and the recently reported PSM-mec (22 residues). The PSM␣ peptides are encoded by the psm␣ operon, the PSM␤ peptides by the psm␤ operon, and PSM␥ by the hld gene. Notably, the hld gene is embedded within the regulatory RNAIII molecule that is encoded by the agr locus. The gene for PSM-mec was identified in MRSA strains carrying the staphylococcal cassette chromosome mec (SCCmec) types II or III. The expression of all ps...

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Section: S Taphylococcus Aureus Is An Opportunistic Human Pathogen Thatmentioning

confidence: 99%

Distinct Roles of Phenol-Soluble Modulins in Spreading of Staphylococcus aureus on Wet Surfaces

Tsompanidou

Denham

Becher

et al. 2013

Appl Environ Microbiol

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“…18,37,38 Because of its size and lipophilic nature, it has been postulated that glycerol monolaurate is inserted into cytoplasmic membrane and exerts its antibacterial effect by interfering with many transmembrane signal transduction systems. 14,39 The influence of ML-LNCs on S. aureus morphology was studied by transmission electron microscopy ( Figure 4). TE micrographs of control (untreated bacteria - Figure 4A) showed proliferating cells that were uniformly shaped with intact cell walls and well-defined cell membranes.…”

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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“…The structure of GML is comprised of a monoester of glycerol and the fatty acid lauric acid, and GML is the most commonly studied member of a class of fatty acid monoesters with antimicrobial properties. GML inhibits the production of gram positive exotoxins such as S. aureus (hemolysins, superantigens [TSST-1 and SEs], and exfoliative toxins), β-hemolytic streptococci (hemolysins and superantigens [SPEs]) (22,23), and Bacillus anthracis (anthrax toxin [protective antigen, lethal factor, and edema factor]) at the cellular level of transcription (24). GML is considered to inhibit transcription by blocking signal transduction in bacterial cells.…”

mentioning

confidence: 99%

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

Peterson

Schlievert

2006

Biochemistry

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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 ug/ml) inhibited superantigen (5 ug/ml) immunoproliferation, as determined by inhibition of 3 H-thymidine incorporation into DNA of human peripheral blood mononuclear cells (1 × 10 6 cells/ml) as well as phospholipase Cγ1, suggesting inhibition of signal transduction. The compound (20 ug/ml) prevented superantigen (100 ug/ml) induced cytokine secretion by human vaginal epithelial cells (HVECs) as measured by ELISA. GML (250 ug) inhibited rabbit lethality due to TSST-1 administered vaginally. GML (10 ug/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 non-toxic to mammalian cells (up to 100 ug/ml) and rabbits (250 ug). GML stabilized mammalian cell membranes, as erythrocyte lysis was reduced in the presence of hypotonic aqueous solutions (0 to 0.05 M saline) or staphylococcal α and β-hemolysins when erythrocytes were pretreated with GML. GML may be useful in management of gram positive exotoxin illnesses; its action appears to be membrane stabilization with inhibition of signal transduction.Many gram positive bacterial pathogens produce exotoxins that are potential agents of bioterrorism and contribute to their abilities to cause human diseases (1-3). Examples include anthrax toxin made by Bacillus anthracis (2), superantigens produced by Staphylococcus aureus, including staphylococcal enterotoxins (SEs) 1 and toxic shock syndrome toxin-1 (TSST-1) (1), and superantigens produced by group A streptococci, including streptococcal pyrogenic exotoxins (SPEs) (3). Other exotoxins, such as staphylococcal α and β-hemolysins and streptolysins, are not agents of bioterrorism but have adjunct roles in virulence and can be used as model toxins to study mechanisms of cellular toxicity.

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Glycerol monolaurate inhibits the production of beta-lactamase, toxic shock toxin-1, and other staphylococcal exoproteins by interfering with signal transduction

Cited by 143 publications

References 28 publications

Distinct Roles of Phenol-Soluble Modulins in Spreading of Staphylococcus aureus on Wet Surfaces

Distinct Roles of Phenol-Soluble Modulins in Spreading of Staphylococcus aureus on Wet Surfaces

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

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

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