Phenol group of terpenoids is crucial for antibacterial activity upon ion leakage

Plant tissues are natural sources of bioactive molecules to control pathogens that cause infections in plants and humans, as they contain secondary metabolites with antibacterial activities. Especially, terpenoids are responsible for the protection of various plants against herbivores and pathogens. In this study, we studied the antibacterial activity of 12 different terpenoid or related structures in a comparative way and revealed that the phenolic terpenoids are superior to other substituted derivatives against both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacteria. We also aimed to analyse effect of these compounds on the bacteria cell wall structure and maintenance of homeostasis. We observed an immediate loss of cell membrane integrity and ion leakage upon treatment of both Gram-negative and Gram-positive cells with phenolic terpenoids carvacrol and thymol. After prolonged treatment, leakage of genetic material and increase of membrane permeability for molecules were also observed. Hydroxyl group of the phenol moiety was essential for this effect, since neither the O-methyl derivatives nor the benzylic partners were as effective. We thus propose that perturbation of ion homeostasis upon increase in cell wall permeability is key for the action of terpenoids against bacteria cells.