A derivative of butyric acid, the fermentation metabolite of staphylococcus epidermidis, inhibits the growth of a staphylococcus aureus strain isolated from atopic dermatitis patients

Supitchaya Traisaeng, Deron Raymond Herr, Hsin Jou Kao, Tsung Hsien Chuang, Chun Ming Huang

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

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.

Original languageEnglish
Article number311
JournalToxins
Volume11
Issue number6
DOIs
StatePublished - Jun 2019

Keywords

  • Atopic dermatitis
  • Butyric acid derivative
  • Fermentation
  • Microbiome
  • S. aureus

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