The natural plant compound carvacrol as an antimicrobial and anti-biofilm agent: mechanisms, synergies and bio-inspired anti-infective materials

The natural antimicrobial compound carvacrol shows a high preference for hydrophobic phases. The partition coefficients of carvacrol in both octanol-water and liposome-buffer phases were determined (3.64 and 3.26, respectively). Addition of carvacrol to a liposomal suspension resulted in an expansion of the liposomal membrane. Maximum expansion was observed after the addition of 0.50 micromol of carvacrol/mg of L-alpha-phosphatidylethanolamine. Cymene, a biological precursor of carvacrol which lacks a hydroxyl group, was found to have a higher preference for liposomal membranes, thereby causing more expansion. The effect of cymene on the membrane potential was less pronounced than the effect of carvacrol. The pH gradient and ATP pools were not affected by cymene. Measurement of the antimicrobial activities of compounds similar to carvacrol (e.g., thymol, cymene, menthol, and carvacrol methyl ester) showed that the hydroxyl group of this compound and the presence of a system of delocalized electrons are important for the antimicrobial activity of carvacrol. Based on this study, we hypothesize that carvacrol destabilizes the cytoplasmic membrane and, in addition, acts as a proton exchanger, thereby reducing the pH gradient across the cytoplasmic membrane. The resulting collapse of the proton motive force and depletion of the ATP pool eventually lead to cell death.

Implant infections in orthopaedics, as well as in many other medical fields, are chiefly caused by staphylococci. The ability of growing within a biofilm enhances the chances of staphylococci to protect themselves from host defences, antibiotic therapies, and biocides. Advances in scientific knowledge on structural molecules (exopolysaccharide, proteins, teichoic acids, and the most recently described extracellular DNA), on the synthesis and genetics of staphylococcal biofilms, and on the complex network of signal factors that intervene in their control are here presented, also reporting on the emerging strategies to disrupt or inhibit them. The attitude of polymorphonuclear neutrophils and macrophages to infiltrate and phagocytise biofilms, as well as the ambiguous behaviour exhibited by these innate immune cells in biofilm-related implant infections, are here discussed. Research on anti-biofilm biomaterials is focused, reviewing materials loaded with antibacterial substances, or coated with anti-adhesive/anti-bacterial immobilized agents, or surfaced with nanostructures. Latter approaches appear promising, since they avoid the spread of antibacterial substances in the neighbouring tissues with the consequent risk of inducing bacterial resistance. Copyright © 2012 Elsevier Ltd. All rights reserved.

Thymol (2-isopropyl-5-methylphenol) is the main monoterpene phenol occurring in essential oils isolated from plants belonging to the Lamiaceae family (Thymus, Ocimum, Origanum, and Monarda genera), and other plants such as those belonging to the Verbenaceae, Scrophulariaceae, Ranunculaceae, and Apiaceae families. These essential oils are used in the food industry for their flavouring and preservative properties, in commercial mosquito repellent formulations for their natural repellent effect, in aromatherapy, and in traditional medicine for the treatment of headaches, coughs, and diarrhea. Many different activities of thymol such as antioxidant, anti-inflammatory, local anaesthetic, antinociceptive, cicatrizing, antiseptic, and especially antibacterial and antifungal properties have been shown. This review aims to critically evaluate the available literature regarding the antibacterial and antifungal effects of thymol.