Interaction of Four Monoterpenes Contained in Essential Oils with Model Membranes: Implications for Their Antibacterial Activity
Abstract
The present article reports the antimicrobial efficacy of four monoterpenes (thymol, carvacrol, p-cymene, and gamma-terpinene) against the Gram-positive bacterium Staphylococcus aureus and the Gram-negative bacterium Escherichia coli. For a better understanding of their mechanism of action, the damage caused by these four monoterpenes on biomembranes was evaluated by monitoring the release, following exposure to the compounds under study, of the water-soluble fluorescent marker carboxyfluorescein (CF) from large unilamellar vesicles (LUVs) with different lipidic composition (phosphatidylcholine, PC, phosphatidylcholine/phosphatidylserine, PC/PS, 9:1; phosphatidylcholine/stearylamine, PC/SA, 9:1). Furthermore, the interaction of these terpenes with dimyristoylphosphatidylcholine multilamellar vesicles as model membranes was monitored by means of differential scanning calorimetry (DSC) technique. Finally, the results were related also with the relative lipophilicity and water solubility of the compounds examined. We observed that thymol is considerably more toxic against S. aureus than the other three terpenes, while carvacrol and p-cymene are the most inhibitory against E. coli. Thymol and carvacrol, but not gamma-terpinene and p-cymene, caused a concentration-dependent CF leakage from all kinds of LUVs employed; in particular, thymol was more effective on PC and PC/SA LUVS than on PC/PS vesicles, while carvacrol challenge evoked a CF leakage from PC/PS LUVs similar to that induced from PC/SA LUVs, and lower than that measured with PC vesicles. Concerning DSC experiments, these four terpenes caused a decrease in Tm and (especially carvacrol and p-cymene) DeltaH values, very likely acting as substitutional impurities. Taken together, our findings lead us to speculate that the antimicrobial effect of thymol, carvacrol, p-cymene, and gamma-terpinene may result, partially at least, from a gross perturbation of the lipidic fraction of the plasmic membrane of the microorganism. In addition to being related to the physicochemical characteristics of the compounds (such as lipophilicity and water solubility), this effect seems to be dependent on the lipidic composition and net surface charge of the microbic membranes. Furthermore, the compounds might cross the cell membranes, thus penetrating into the interior of the cell and interacting with intracellular sites critical for antibacterial activity.
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Carvacrol's effect on membrane permeability was confirmed by monitoring the efflux of H+, K+, carboxyfluorescein and ATP and the influx of nucleic acid stains.
“Carvacrol’s effect on membrane permeability was confirmed monitoring the efflux of H+, K+, carboxyfluorescein and ATP and the influx of nucleic acid stains [13,20,24,28,36].”
From Effect of essential oils on pathogenic bacteria (2013) · cites this paper as [24]
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- Authors
- Cristani, M., D'Arrigo, M., Mandalari, G., Castelli, F., Sarpietro, M. G., Micieli, D., Venuti, V., Bisignano, G., Saija, A., & Trombetta, D.
- Affiliations
- University of Messina (IT)
- Department Farmaco-Biologico, School of Pharmacy, University of Messina, Contrada Annunziata, 98168 Messina, Italy, and Department of Chemical Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy
- Corresponding author
- Trombetta, Domenico
- ORCID
- Venue
- Journal of Agricultural and Food Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2007-06-30
- Volume
- 55
- Issue
- 15
- Pages
- 6300-6308
- ISSN
- 0021-8561 (ISSN-L)
- 1520-5118
- OpenAlex
- W2004870695
- Cited by
- 671
- References
- 51
- Citations by year
- 2026: 39 · 2025: 31 · 2024: 33 · 2023: 37 · 2022: 47 · 2021: 51 · 2020: 56 · 2019: 57 · 2018: 40 · 2017: 49 · 2016: 42 · 2015: 37 · 2014: 32 · 2013: 40 · 2012: 22
- FWCI
- 19.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Agricultural and Food Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Essential Oils and Antimicrobial Activity
- Physical Sciences › Chemistry › Organic Chemistry › Antimicrobial agents and applications
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Keywords
- monoterpenes, thymol, carvacrol, p-cymene, γ-terpinene, essential oils, antibacterial activity, Staphylococcus aureus, Escherichia coli, membrane damage, lipid vesicles, carboxyfluorescein leakage, membrane fluidity, lipophilicity, water solubility, mechanism of action
- MeSH terms
- Cyclohexane Monoterpenes, Cymenes, Anti-Bacterial Agents, Escherichia coli, Oils, Volatile, Staphylococcus aureus, Thymol, Monoterpenes, Unilamellar Liposomes
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