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Open AccessArticle

A Derivative of Butyric Acid, the Fermentation Metabolite of Staphylococcus epidermidis, Inhibits the Growth of a Staphylococcus aureus Strain Isolated from Atopic Dermatitis Patients

1
Department of Life Sciences, National Central University, Taoyuan 32001, Taiwan
2
Department of Pharmacology, National University of Singapore, Singapore 117600, Singapore
3
Department of Biomedical Sciences and Engineering, National Central University, Taoyuan 32001, Taiwan
4
Immunology Research Center, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan
5
Department of Dermatology, University of California, San Diego 3525 John Hopkins Court, Rm276, San Diego, CA 92121, USA
*
Author to whom correspondence should be addressed.
Toxins 2019, 11(6), 311; https://doi.org/10.3390/toxins11060311
Received: 18 April 2019 / Revised: 24 May 2019 / Accepted: 24 May 2019 / Published: 31 May 2019
(This article belongs to the Special Issue Staphylococcus aureus Toxins)
The microbiome is a rich source of metabolites for the development of novel drugs. Butyric acid, for example, is a short-chain fatty acid fermentation metabolite of the skin probiotic bacterium Staphylococcus epidermidis (S. epidermidis). Glycerol fermentation of S. epidermidis resulted in the production of butyric acid and effectively hindered the growth of a Staphylococcus aureus (S. aureus) strain isolated from skin lesions of patients with atopic dermatitis (AD) in vitro and in vivo. This approach, however, is unlikely to be therapeutically useful since butyric acid is malodorous and requires a high concentration in the mM range for growth suppression of AD S. aureus. A derivative of butyric acid, BA–NH–NH–BA, was synthesized by conjugation of two butyric acids to both ends of an –NH–O–NH– linker. BA–NH–NH–BA significantly lowered the concentration of butyric acid required to inhibit the growth of AD S. aureus. Like butyric acid, BA–NH–NH–BA functioned as a histone deacetylase (HDAC) inhibitor by inducing the acetylation of Histone H3 lysine 9 (AcH3K9) in human keratinocytes. Furthermore, BA–NH–NH–BA ameliorated AD S. aureus-induced production of pro-inflammatory interleukin (IL)-6 and remarkably reduced the colonization of AD S. aureus in mouse skin. These results describe a novel derivative of a skin microbiome fermentation metabolite that exhibits anti-inflammatory and S. aureus bactericidal activity. View Full-Text
Keywords: atopic dermatitis; butyric acid derivative; fermentation; microbiome; S. aureus atopic dermatitis; butyric acid derivative; fermentation; microbiome; S. aureus
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Traisaeng, S.; Herr, D.R.; Kao, H.-J.; Chuang, T.-H.; Huang, C.-M. A Derivative of Butyric Acid, the Fermentation Metabolite of Staphylococcus epidermidis, Inhibits the Growth of a Staphylococcus aureus Strain Isolated from Atopic Dermatitis Patients. Toxins 2019, 11, 311.

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