Natural Terpenes Influence the Activity of Antibiotics against Isolated Mycobacterium tuberculosis

Abstract

Objective: In this study, we aimed to describe the influence of natural terpenes on the antimycobacterial activity of first-line tuberculostatic drugs against isolated Mycobacterium tuberculosis. Materials and Methods: The natural terpenes used in this study were R-limonene, S-limonene, myrcene, sabinene, α-pinene, and β-elemene. The values of the minimum inhibitory concentration (MIC) for these terpenes, as well as for combinations of terpenes with tuberculostatic antibiotics (ethambutol, isoniazid, and rifampicin), were determined using a tube log2 dilution method in the range of 125-0.059 μg/mL. Results:S-limonene had a strong synergistic effect with all tested antibiotics (MIC decreased from 16 to 0.475 μg/mL for ethambutol, from 16 to 0.237 μg/mL for rifampicin, and from 32 to 0.475 μg/mL for isoniazid). Combinations of myrcene, R-limonene, β-elemene, and sabinene with tuberculostatic antibiotics resulted in a decreased MIC of the antibiotics (from 3.9 to 0.475 μg/mL for ethambutol, from 15 to 0.475 μg/mL for isoniazid, and from 0.475 to 0.237 μg/mL for rifampicin) while combinations of α-pinene with ethambutol and isoniazid resulted in increased MIC values (from 16 to 125 μg/mL for ethambutol, and from 32 to 125 μg/mL for isoniazid). Rifampicin had a synergistic increase in activity with all the tested compounds. Conclusions: Our study showed that terpenes enhance the activity of tuberculostatic antibiotics.