Inhibitory Effects on Staphylococcus aureus Sortase A by Aesculus sp. Extracts and Their Toxicity Evaluation

Area of Science:

• Microbiology and Biochemistry
• Natural Product Chemistry
• Toxicology

Background:

• Antivirulence strategies offer an alternative to traditional antibiotics by targeting bacterial pathogenicity factors.
• Sortase A is a critical enzyme in Gram-positive bacteria, essential for anchoring surface virulence factors.
• Extracts from Aesculus species (horse chestnut) are explored for their potential antimicrobial and antivirulence properties.

Purpose of the Study:

• To evaluate the inhibitory activity of Aesculus species extracts against Staphylococcus aureus sortase A.
• To determine the polyphenol content and chemical profile of the extracts.
• To assess the toxicity of the extracts using in vitro (fibroblast cell line) and in vivo (Daphnia magna) models.

Main Methods:

• Preparation of ethanol and water extracts from four Aesculus species: A. pavia, A. parviflora, A. x carnea, and A. hippocastanum.
• High-Performance Liquid Chromatography (HPLC) for extract characterization and Folin-Ciocalteu assay for total polyphenol content.
• Enzyme inhibition assays to determine the half maximal inhibitory concentration (IC50) against sortase A, and toxicity assessments using median lethal concentration (LC50) in Daphnia magna and fibroblast cell lines.

Main Results:

• The half maximal inhibitory concentration (IC50) values for sortase A inhibition ranged from 82.70 to 304.31 µg/mL.
• The water extract of Aesculus pavia demonstrated the highest inhibitory activity against sortase A.
• Aesculus pavia water extract exhibited low toxicity to human fibroblasts and Daphnia magna, with no significant toxicity observed at 500 µg/mL in fibroblast assays.

Conclusions:

• Aesculus pavia water extract is a potent inhibitor of Staphylococcus aureus sortase A.
• The extract displays a favorable low toxicity profile, making it a promising candidate for developing novel antivirulence therapies.
• Further research into this extract could lead to new strategies for combating bacterial infections without promoting antibiotic resistance.