Study of the antimicrobial activity of carvacrol and its mechanism of action against drug-resistant bacteria.

Drug-resistant bacterial infections have been one of the critical health issues encountered worldwide currently because most conventional antibiotics are losing their effectiveness in clinical treatments. It is thus urgently to identify new antibiotics or alternatives against drug-resistant bacteria. For this purpose, we attempted to seek active compounds from commercially available natural products, which may be one of the fast-tracks to address the drug-resistant bacterial infections. In the present study, we investigated the antibacterial activity, antibacterial mechanism and synergistic effects of carvacrol against a panel of drug-resistant bacteria, including some clinical isolates. The results show that carvacrol (cymophenol), a monoterpenoid phenol, has excellent antibacterial activity. The MIC values against the bacteria examined are found to be 4-16 μg/mL. Our results also suggested that carvacrol might not likely to induce drug-resistance. More importantly, when carvacrol combined with first-line antibiotics, it exhibited good synergistic effects against drug-resistant bacteria. Moreover, in morphological studies, carvacrol could cause B. subtilis 168 elongation and S. aureus BAA-41 enlargement, which may suggest an antibacterial mechanism possibly correlated with the inhibition of bacterial cell division. We further demonstrated that carvacrol facilitated the polymerization of FtsZ that is a critically important protein for regulating bacterial cell division. Furthermore, molecular modeling predicted that carvacrol could interact with T7-loop of FtsZ. The findings of this study suggest that carvacrol may be a potential inhibitor of FtsZ and it could be utilized to combat drug-resistant bacteria in combination with existing antibiotics.