A novel volatile staphyloxanthin biosynthesis inhibitor against Staphylococcus aureus

Abstract

In the present research, volatile organic compounds (VOCs) of garlic/mustard oil macerate (GMM) (garlic clove and mustard oil in the ratio of 1:4, heated at 80 ^OC for 4 h) were found to enhance the antibacterial activity of antibiotics (gentamycin, 41.17 %; kanamycin, 38.89 %, and streptomycin, 43.75 %) against S. aureus. The mechanism behind the enhancement of S. aureus's sensitivity to antibiotics may be due to the reduction of antibiotic resistance. On evaluating one of the well-known antibiotic resistance mechanisms of S. aureus, the ability to produce staphyloxanthin, it has been observed that the VOCs of GMM alone can decrease staphyloxanthin (44.23 ± 0.14 %) production. This decrease in staphyloxanthin production thereby increasing sensitivity to antibiotics, may be assigned to the compounds present in the VOCs of GMM. The major VOCs present in the GMM were identified as allicin, ajoene, vinyl dithiin, allyl isothiocyanate (AITC) and sinigrin. The order of binding of VOCs with dehydroxysqualene synthase (crtM) protein, which is important in staphyloxanthin production of S. aureus, was found to be sinigrin > ajoene > allicin > dithiin > AITC. Further, a decrease in staphyloxanthin production was found to increase the membrane fluidity of S. aureus as validated by Fourier-transformed infrared spectroscopy and scanning electron microscopy and this may allow antibiotics to enter inside the bacterial cell more rapidly. Thus, our research indicates that the VOCs in GMM may serve as a potential adjuvant when treating S. aureus infection.