Marine Fungal Cerebroside Flavuside B Protects HaCaT Keratinocytes against Staphylococcus aureus Induced Damage

Mar Drugs. 2021 Sep 29;19(10):553. doi: 10.3390/md19100553.

Abstract

Cerebrosides are glycosylated sphingolipids, and in mammals they contribute to the pro-/anti-inflammatory properties and innate antimicrobial activity of the skin and mucosal surfaces. Staphylococcus aureus infection can develop, not only from minor scratches of the skin, but this pathogen can also actively promote epithelial breach. The effect of cerebroside flavuside B from marine sediment-derived fungus Penicillium islandicum (Aniva Bay, the Sea of Okhotsk) on viability, apoptosis, total caspase activity, and cell cycle in human epidermal keratinocytes HaCaT line co-cultivated with S. aureus, as well as influence of flavuside B on LPS-treated HaCaT cells were studied. Influence of flavuside B on bacterial growth and biofilm formation of S. aureus and its effect on the enzymatic activity of sortase A was also investigated. It was found S. aureus co-cultivated with keratinocytes induces caspase-depended apoptosis and cell death, arrest cell cycle in the G0/G1 phase, and increases in cellular immune inflammation. Cerebroside flavuside B has demonstrated its antimicrobial and anti-inflammatory properties, substantially eliminating all the negative consequences caused by co-cultivation of keratinocytes with S. aureus or bacterial LPS. The dual action of flavuside B may be highly effective in the treatment of bacterial skin lesions and will be studied in the future in in vivo experiments.

Keywords: Staphylococcus aureus; anti-inflammatory activity; antibacterial activity; apoptosis; biofilm formation; cerebroside; marine fungi; secondary metabolites; sortase A.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Aquatic Organisms
  • Cerebrosides / pharmacology*
  • Glycosphingolipids / pharmacology*
  • HaCaT Cells / drug effects
  • Humans
  • Keratinocytes / drug effects*
  • Penicillium*
  • Skin Diseases, Bacterial / prevention & control*
  • Staphylococcal Infections / prevention & control*
  • Staphylococcus aureus / drug effects*

Substances

  • Anti-Bacterial Agents
  • Cerebrosides
  • Glycosphingolipids
  • flavuside B