A novel volatile staphyloxanthin biosynthesis inhibitor against Staphylococcus aureus

Area of Science:

• Microbiology
• Pharmacology
• Natural Products Chemistry

Background:

• Antibiotic resistance in Staphylococcus aureus (S. aureus) poses a significant global health threat.
• Staphyloxanthin production is a key mechanism contributing to S. aureus antibiotic resistance.
• Natural compounds are being explored as potential adjuvants to overcome antibiotic resistance.

Purpose of the Study:

• To investigate the effect of volatile organic compounds (VOCs) from garlic/mustard oil macerate (GMM) on the antibacterial activity of antibiotics against S. aureus.
• To elucidate the mechanism by which GMM VOCs enhance antibiotic sensitivity, specifically focusing on staphyloxanthin production.
• To identify key compounds within GMM VOCs responsible for these effects.

Main Methods:

• Preparation of garlic/mustard oil macerate (GMM) and extraction of its volatile organic compounds (VOCs).
• Assessment of GMM VOCs' impact on the antibacterial activity of gentamycin, kanamycin, and streptomycin against S. aureus.
• Quantification of staphyloxanthin production in S. aureus treated with GMM VOCs.
• Identification of major VOCs in GMM using gas chromatography-mass spectrometry (GC-MS).
• In silico analysis of VOC binding affinity to dehydroxysqualene synthase (crtM).
• Validation of changes in S. aureus membrane fluidity using Fourier-transformed infrared spectroscopy and scanning electron microscopy.

Main Results:

• GMM VOCs significantly enhanced the antibacterial activity of gentamycin (41.17%), kanamycin (38.89%), and streptomycin (43.75%) against S. aureus.
• GMM VOCs alone reduced staphyloxanthin production by 44.23% in S. aureus.
• Key identified VOCs included allicin, ajoene, vinyl dithiin, allyl isothiocyanate (AITC), and sinigrin, with sinigrin showing the highest binding affinity to crtM.
• Reduced staphyloxanthin production led to increased bacterial membrane fluidity, facilitating antibiotic entry.

Conclusions:

• VOCs from GMM exhibit potent antibacterial-enhancing properties against S. aureus.
• GMM VOCs effectively inhibit staphyloxanthin production, a crucial mechanism for S. aureus antibiotic resistance.
• The identified VOCs, particularly sinigrin, ajoene, and allicin, are likely responsible for the observed effects.
• GMM VOCs demonstrate significant potential as an adjuvant therapy to combat S. aureus infections and overcome antibiotic resistance.