Chemoinformatic Investigation of Antibiotic Antagonism: The Interference of Thymus glabrescens Essential Oil Components with the Action of Streptomycin

Given the importance of Thymus glabrescens as a useful antibacterial remedy, we have evaluated the antibacterial and streptomycin-modifying activity of Thymus glabrescens essential oil, geraniol, geranyl acetate and thymol. It was shown that all substance-streptomycin combinations produced predominantly antagonistic interactions. Furthermore, combinations between geraniol and thymol showed dominant additive effect. Chemoinformatics results, combined with experimental data, suggest that antagonistic interactions with streptomycin were not a consequence of the antimicrobial action at the same target, but an outcome of the membrane impairment, followed by the membrane potential/proton motive force dissipation, which decreased the streptomycin uptake. Furthermore, the membrane toxicity of geraniol and thymol was confirmed by their additive antibacterial interactions and parameters of their penetration and accumulation throughout a cell membrane. This study should greatly help in an intelligent and a controlled pharmacomodulation of antibiotics.