Antifungal, antibacterial, and anti-inflammatory activity of glycerol dithionomonolaurate, an analog of glycerol monolaurate
Bibliographic record
Abstract
ABSTRACT Glycerol dithionomonolaurate (NB2) is an analog of the natural antimicrobial compound glycerol monolaurate (GML) with enhanced antimicrobial activity. The advantage of NB2 over GML is the presence of a dithionate to greatly reduce microbial cleavage through glycerol ester hydrolases, such as Staphylococcus aureus lipase. NB2 exhibited antimicrobial activity against Candida fungal species, including Candida auris , with comparable minimum bactericidal concentration (MBC) and minimum inhibitory concentration (MIC) of 50–100 µg/mL compared to 250–500 µg/mL for GML. NB2 exhibited a broad range of antibacterial activity including both gram-positive and gram-negative organisms, while sparing normal microbiome lactobacilli. When 10 8 C. auris and 10 9 S. aureus were incubated on Todd Hewitt agar plates in the presence of two times the MBC for NB2, no resistant colonies grew, likely the result of the large number of antimicrobial targets inhibited. Like GML, NB2 inhibited exotoxin production at non-antibacterial concentrations. NB2 exhibited anti-staphylococcal activity when tested topically on a dermatitis skin model on rabbits. NB2 inhibited the production of chemokines (interleukin-8 and macrophage inflammatory protein-3α) by human vaginal epithelial cells, suggesting anti-inflammatory activity. Unlike clear GML solutions, NB2 was pale yellow. The absorption spectrum of NB2 was not sufficient to raise Food and Drug Administration concerns over phototoxicity. Collectively, the data suggest that NB2 could become a useful topical agent for the prevention of both fungal and bacterial infections as a dual-active anti-infective, killing microbes and reducing harmful inflammation, such as seen in atopic dermatitis. IMPORTANCE Fungi and many bacteria commonly develop resistance to antimicrobial agents or have inherent resistance. Many microbes initiate infections through the skin and mucous membranes, in part by producing toxins and causing harmful inflammation. We describe a novel topical antimicrobial agent, glycerol dithionomonolaurate (NB2), effective against Candida and a wide range of gram-positive and gram-negative bacteria; the compound did not kill normal microbiome lactobacilli. NB2 is likely to have many microbial targets for killing, suggesting resistance to the molecule may not develop. At sub-antibacterial concentrations, glycerol dithionomonolaurate inhibited exotoxin production by Staphylococcus aureus . The molecule was not inactivated by staphylococcal lipase. Glycerol dithionomonolaurate effectively treated S. aureus dermatitis in a rabbit skin model and reduced chemokine production by human epithelial cells. Glycerol dithionomonolaurate may prove useful to treat many types of skin and mucous membrane infections by both antimicrobial and anti-inflammatory activities, such as in atopic dermatitis.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".