Harnessing Monoterpenes and Monoterpenoids as Weapons against Antimicrobial Resistance

Amanda Shen-Yee Kong; Swee-Hua Erin Lim; Wan-Hee Cheng; Mohd Hafis Yuswan; Ngai-Paing Tan; Kok-Song Lai

doi:10.33073/pjm-2025-010

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Harnessing Monoterpenes and Monoterpenoids as Weapons against Antimicrobial Resistance

Polish Journal of Microbiology

Volume 74 (2025): Issue 1 (March 2025)

By: Amanda Shen-Yee Kong, Swee-Hua Erin Lim, Wan-Hee Cheng, Mohd Hafis Yuswan, Ngai-Paing Tan and Kok-Song Lai

Open Access

|Mar 2025

Figures & Tables

Chemical structures of monoterpenes discussed in this review, sourced from the PubChem database.

A schematic representation of mechanisms of action of monoterpenes targeting MDR bacteria.
The diagram was created using Inkscape 1.3.2.

Table I

Mechanism of action of monoterpenes against tested pathogens.

Chemical compounds	Tested pathogen	Mechanisms of action	References
Eugenol	Staphylococcus aureus	Inhibition of efflux pump	Macêdo et al. 2022
Eugenol	Staphylococcus aureus	Inhibition of norA efflux pump	Muniz et al. 2021
Eugenol α-Bromo-trans-cinnamaldehyde	Staphylococcus aureus	Gene expression reduction linked to intracellular adhesion	Mastoor et al. 2022
Eugenol	Methicillin-resistant Staphylococcus aureus	Downregulation of luxS gene Inhibition of biofilm production Enhancement of secondary metabolites Upregulation of argC protein	Buru et al. 2022
Eugenol	Methicillin-resistant Staphylococcus aureus	Downregulation of biofilm-related genes (sarA, icaA, icaD) Reduction of polysaccharide accumulation and cell adhesion	El-Far et al. 2021
Carvacrol	Staphylococcus aureus Pseudomonas fluorescens	Targeted extracellular polymeric substances Disruption of biofilm structures	Wang et al. 2020b.
Eugenol Geraniol	Acinetobacter baumannii	Reduction in exopolysaccharide production Disruption and inhibition of biofilm Downregulation of csuE gene	Choudhary et al. 2022
p-Cymene	Campylobacter jejuni	Inhibition of efflux pump	Šimunović et al. 2020
Carvacrol	Pseudomonas aeruginosa Enterococcus faecalis	Cell membrane destruction Leakage of the intercellular pool Anti-biofilm properties Increased extracellular K+ ions concentrations	Mechmechani et al. 2022
Carvacrol Thymol	Salmonella Thyphimurium	Anti-inflammatory effects Anti-oxidant properties Enhanced epithelial barrier integrity Reduction of bacterial translocation Improved transepithelial electrical resistance Inhibited bacterial growth	Giovagnoni et al. 2020
Eugenol	Extended-spectrum β-lactamases-quinoloneresistant strains of Klebsiella pneumoniae	Induced shrinkage of cell surfaces Diminished cytoplasm Triggered cellular stress and autolysis	Dhara and Tripathi 2020
Eugenol	Carbapenem-resistant Klebsiella pneumoniae (CRKP)	Disruption of cell membrane Reduction in intracellular pH and ATP levels Cell membrane hyperpolarization Downregulation of biofilm-related genes (pgaA, luxS, wbbM, wzm) Upregulation of mrkA gene	Qian et al. 2020
Carvacrol	Extended-spectrum beta-lactamases Escherichia coli	Disintegration of bacterial cell membranes Elevation of reactive oxygen species levels Protected macrophage cells from bacterial invasion Increased the release of K+ ions, ATP, and cellular DNA Anti-biofilm properties	Khan et al. 2020
Carvacrol Thymol Eugenol Methyl eugenol	Candida albicans	Reduced proteinase production	Shaban et al. 2020
Carvacrol Thymol Eugenol Methyl eugenol	Candida auris	Reduced proteinase production and host cell adherence	Shaban et al. 2020
Carvacrol	Candida auris	Induced oxidative stress Increased CAT, SOD and GPx enzyme activity Decreased GR and GST enzyme activity Caused membrane disintegration	Ismail et al. 2022

Table II

Comprehensive summary of MIC values of monoterpenes against AMR pathogens, grouped as Gram-positive, Gram-negative, and fungal pathogens.

Tested pathogens	Chemical compounds	MIC/Sensitivity	References
Gram-positive bacteria
Bacillus subtilis	Limonene	0.048 μg/ml	Noumi et al. 2023
Listeria monocytogenes	Limonene	0.048 μg/ml	Noumi et al. 2023
Enterococcus sp.	Thymol Carvacrol Geraniol Limonene Eugenol Cinnamaldehyde	200–450 μg/ml 100–450 μg/ml 100–350 μg/ml 100–450 μg/ml 200–450 μg/ml 10–50 μg/ml	Caballero Gómez et al. 2022
Vancomycin-sensitive Enterococcus (VSE)	Carvacrol Cuminaldehyde Linalool p-Cymene γ-Terpinene	593.37 μg/ml 19919562 μg/ml 35199850 μg/ml 8599475.4 μg/ml 17060082.9 μg/ml	Owen et al. 2019
Vancomycin-resistant Enterococcus (VRE)	Carvacrol Cuminaldehyde Linalool p-Cymene γ-Terpinene	593369 μg/ml 79679730 μg/ml 8799962.5 μg/ml 8599475.4 μg/ml 17060082.9 μg/ml	Owen et al. 2019
Staphylococcus sp.	Thymol Carvacrol Geraniol Limonene Eugenol Cinnamaldehyde	200–400 μg/ml 200–400 μg/ml 100–400 μg/ml 100–400 μg/ml 300–400 μg/ml 10–50 μg/ml	Caballero Gómez et al. 2022
Staphylococcus aureus	Thymol Carvacrol Limonene α-Pinene β-Pinene p-Cymene 1,8-Cineole Limonene Fenchone Linalool Camphor cis-Verbenol Borneol Terpinen-4-ol Verbenone Carvone Eugenol Linalyl acetate trans-Anethole Menthone	72–800 μg/ml 256–3200 μg/ml 0.048 μg/ml 11.88 μg/ml 10.13 μg/ml 10.25 μg/ml 5.63–115100 μg/ml 2.63 μg/ml 4.25 μg/ml 2.88–6800 μg/ml 7.63 μg/ml 2.38 μg/ml 3.75 μg/ml 3.13 μg/ml 5.88 μg/ml 11.38 μg/ml 24–11100 μg/ml 46900 μg/ml 494000 μg/ml 27900 μg/ml	Kwiatkowski et al. 2020; Sayout et al. 2020; Sousa Silveira et al. 2020; Macêdo et al. 2022; Noumi et al. 2023; Sharma et al. 2023
Methicillin-susceptible Staphylococcus aureus	Carvacrol Cuminaldehyde Linalool p-Cymene γ-Terpinene	297435.6 μg/ml 4979520 μg/ml 17599925 μg/ml 1075102.2 μg/ml 8529360.3 μg/ml	Owen et al. 2019
Methicillin-resistant Staphylococcus aureus	Carvacrol Cuminaldehyde Linalool p-Cymene γ-Terpinene	148717.8 μg/ml 9960522 μg/ml 8799962.5 μg/ml 2150204.4 μg/ml 17060082.9 μg/ml	Owen et al. 2019
Mupirocin-susceptible Staphylococcus aureus	1,8-cineole Eugenol Carvacrol Linalool (–)-Menthone Linalyl acetate trans-Anethole	307000 μg/ml 2080 μg/ml 950 μg/ml 6800 μg/ml 27910 μg/ml 450500 μg/ml 494000 μg/ml	Kwiatkowski et al. 2019
Mupirocin-resistant Staphylococcus aureus	1,8-cineole Eugenol Carvacrol Linalool (–)-Menthone Linalyl acetate trans-Anethole	57560 μg/ml 8340 μg/ml 480 μg/ml 2830 μg/ml 6980 μg/ml 450500 μg/ml 494000 μg/ml	Kwiatkowski et al. 2019
Staphylococcus pseudintermedius	Thymol Carvacrol	100–200 μg/ml 146–292 μg/ml	Sim et al. 2019
β-haemolytic Streptococcus spp.	Thymol Carvacrol	200–400 μg/ml 146–292 μg/ml	Sim et al. 2019
Streptococcus suis	Cinnamaldehyde Carvacrol Thymol	156.25–312.5 μg/ml 156.25 μg/ml 156.25 μg/ml	de Aguiar et al. 2019
Gram-negative bacteria
Acinetobacter baumannii	α-Pinene Camphene β-Pinene d-3-Carene p-Cymene 1,8-Cineole Limonene γ-Terpinene Fenchone Linalool Camphor cis-Verbenol Borneol Terpinen-4-ol Verbenone Carvone	11.88 μg/ml 20.00 μg/ml 13.50 μg/ml 7.88 μg/ml 5.13 μg/ml 5.63 μg/ml 5.25 μg/ml 4.88 μg/ml 1.06 μg/ml 1.44 μg/ml 10.17 μg/ml 9.50 μg/ml 0.94 μg/ml 0.78 μg/ml 4.70 μg/ml 7.58 μg/ml	Sayout et al. 2020
Campylobacter jejuni	Thymol Carvacrol Thymoquinone p-Cymene γ-Terpinene	31.25 μg/ml 31.25 μg/ml 31.25 μg/ml 1000 μg/ml 1000 μg/ml	Šimunović et al. 2020
Enterobacter aerogenes	β-Pinene 1,8-Cineole Limonene γ–Terpinene Fenchone Linalool Camphor cis-Verbenol Borneol Verbenone Carvone	20.25 μg/ml 2.81 μg/ml 1.31 μg/ml 4.88 μg/ml 2.13 μg/ml 1.44 μg/ml 15.25 μg/ml 2.38 μg/ml 0.94 μg/ml 2.94 μg/ml 5.69 μg/ml	Sayout et al. 2020
Enterobacter cloacae	α-Pinene β-Pinene Myrcene d-3-Carene p-Cymene 1,8-Cineole Limonene γ-Terpinene Fenchone Linalool Camphor cis-Verbenol Borneol Terpinen-4-ol Verbenone Carvone	11.88 μg/ml 5.06 μg/ml 7.75 μg/ml 7.88 μg/ml 4.10 μg/ml 5.63 μg/ml 2.63 μg/ml 6.50 μg/ml 1.70 μg/ml 1.92 μg/ml 6.10 μg/ml 3.17 μg/ml 1.50 μg/ml 3.13 μg/ml 3.36 μg/ml 9.10 μg/ml	Sayout et al. 2020
Ciprofloxacin-resistant Escherichia coli	Carvacrol Cuminaldehyde Linalool p-Cymene γ-Terpinene	297435.6 μg/ml 1244880 μg/ml 8799962.5 μg/ml 1075102.2 μg/ml 34120165.8 μg/ml	Owen et al. 2019
Escherichia coli	Carvacrol Cuminaldehyde Linalool p-Cymene γ-Terpinene Limonene α-Pinene Camphene β-Pinene Myrcene d-3-Carene p-Cymene 1,8-Cineole Limonene γ-Terpinene Fenchone Linalool Camphor cis-Verbenol Borneol Terpinen-4-ol Verbenone Carvone	297435.6 μg/ml 311220 μg/ml 8799962.5 μg/ml 2150204.4 μg/ml 34120165.8 μg/ml 0.048 μg/ml 11.88 μg/ml 15.00 μg/ml 5.06 μg/ml 1.94 μg/ml 7.88 μg/ml 2.56 μg/ml 2.81 μg/ml 2.63 μg/ml 4.88 μg/ml 4.25 μg/ml 2.88 μg/ml 7.63 μg/ml 4.75 μg/ml 3.75 μg/ml 3.13 μg/ml 5.88 μg/ml 11.38 μg/ml	Owen et al. 2019; Sayout et al. 2020; Noumi et al. 2023
Klebsiella oxytoca	β-Pinene 1,8-Cineole Limonene γ-Terpinene Fenchone Linalool Camphor cis-Verbenol Borneol Terpinen-4-ol Verbenone Carvone	13.50 μg/ml 5.63 μg/ml 2.63 μg/ml 4.88 μg/ml 2.13 μg/ml 1.44 μg/ml 10.17 μg/ml 3.17 μg/ml 2.5 μg/ml 6.25 μg/ml 5.88 μg/ml 11.38 μg/ml	Sayout et al. 2020
Klebsiella pneumoniae	Thymol Carvacrol Geraniol α-Pinene Camphene β-Pinene Myrcene d-3-Carene p-Cymene 1,8-Cineole Limonene γ-Terpinene Fenchone Linalool Camphor cis-Verbenol Borneol Terpinen-4-ol Verbenone Carvone	780 μg/ml 130–1910 μg/ml 1740 μg/ml 23.75 μg/ml 30.00 μg/ml 10.13 μg/ml 15.50 μg/ml 7.88 μg/ml 10.25 μg/ml 11.25 μg/ml 2.63 μg/ml 4.88 μg/ml 2.13 μg/ml 3.83 μg/ml 5.08 μg/ml 2.38 μg/ml 0.47 μg/ml 1.56 μg/ml 3.36 μg/ml 15.17 μg/ml	Sayout et al. 2020; de Souza et al. 2021; Kwiatkowski et al. 2022
Malassezia pachydermatis	Thymol Carvacrol Cinnamaldehyde	10–800 μg/ml 10–585 μg/ml 2.5–640 μg/ml	Schlemmer et al. 2019; Sim et al. 2019
Salmonella enterica	Limonene	0.048 μg/ml	Noumi et al. 2023
Salmonella spp.	β-Pinene 1,8-Cineole Limonene γ-Terpinene Fenchone Linalool Camphor cis-Verbenol Terpinen-4-ol Verbenone Carvone	8.10 μg/ml 7.50 μg/ml 2.63 μg/ml 6.50 μg/ml 1.70 μg/ml 2.88 μg/ml 6.10 μg/ml 1.90 μg/ml 3.13 μg/ml 3.92 μg/ml 22.75 μg/ml	Sayout et al. 2020
Shigella flexeneri	Limonene	0.048 μg/ml	Noumi et al. 2023
Proteus mirabilis	Thymol Carvacrol	200 μg/ml 146–292 μg/ml	Sim et al. 2019
Pseudomonas sp.	Thymol Carvacrol Geraniol Limonene Eugenol Cinnamaldehyde	100–300 μg/ml 100–400 μg/ml 100–400 μg/ml 100–300 μg/ml 300–400 μg/ml 10–50 μg/ml	Caballero Gómez et al. 2022
Ciprofloxacin-resistant Pseudomonas aeruginosa	Carvacrol Cuminaldehyde Linalool p-Cymene γ-Terpinene	4749956.4 μg/ml 39840606 μg/ml 140799400 μg/ml 8599475.4 μg/ml 34120165.8 μg/ml	Owen et al. 2019
Pseudomonas aeruginosa	Thymol Carvacrol Cuminaldehyde Linalool p-Cymene γ-Terpinene Limonene β-Pinene	400–800 μg/ml 585–1120 μg/ml 39839124 μg/ml 35199850 μg/ml 8599475.4 μg/ml 68240331.6 μg/ml 0.048 μg/ml 10.13 μg/ml	Owen et al. 2019; Sim et al. 2019; Noumi et al. 2023
Pseudomonas aeruginosa	Limonene Fenchone Linalool Camphor cis-Verbenol Borneol Terpinen-4-ol Verbenone Carvone	2.63 μg/ml 1.70 μg/ml 1.92 μg/ml 6.10 μg/ml 1.58 μg/ml 1.88 μg/ml 3.13 μg/ml 4.70 μg/ml 9.10 μg/ml	Owen et al. 2019; Sim et al. 2019; Noumi et al. 2023
Vibrio vulnificus	Limonene	0.048 μg/ml	Noumi et al. 2023
Vibrio anguillarum	Thymol Carvacrol Eugenol Geraniol Cinnamaldehyde	282413.6 μg/ml 282413.6 μg/ml 308696 μg/ml 1156875 μg/ml 555750 μg/ml	Rossi et al. 2021
Vibrio harveyi	Thymol Carvacrol Eugenol Geraniol Cinnamaldehyde	141206.8 μg/ml 141206.8 μg/ml 308696 μg/ml 1156875 μg/ml 278616 μg/ml	Rossi et al. 2021
Fungal pathogens
Candida albicans	Thymol Carvacrol Eugenol Methyl eugenol (+)-α-Pinene (–)-α-Pinene β-Pinene (+)-Limonene (–)-Limonene (+)-Menthone (–)-Menthone Thujone Piperitone (+)-Carvone (–)-Carvone Camphor (+)-Citronellol (–)-Citronellol (+)-Menthol (–)-Menthol	195–625 μg/ml 43.75–250 μg/ml 500–2000 μg/ml 1250 μg/ml 51767.4–1716498 μg/ml 858249–54927936 μg/ml 213881.1–13731984 μg/ml 8173.8–6865992 μg/ml 8173.8–13731984 μg/ml 3578600–6787000 μg/ml 1789300–28628800 μg/ml 459734.6–7355753.6 μg/ml 239762.25–3732679.6 μg/ml 473193–3785544 μg/ml 473193–3785544 μg/ml 494747.5–3957980 μg/ml 49360–1665900 μg/ml 49360–1665900 μg/ml 221889.2–7125456 μg/ml 221889.2–7125456 μg/ml	Sharifzadeh et al. 2019; Iraji et al. 2020; Shaban et al. 2020; Stringaro et al. 2022; Biernasiuk et al. 2022
Candida auris	Carvacrol Thymol Eugenol Methyl eugenol	125 μg/ml 312 μg/ml 625 μg/ml 1250 μg/ml	Shaban et al. 2020
Candida dubliniensis	(+)-α-Pinene (–)-α-Pinene β-Pinene (+)-Limonene (–)-Limonene (+)-Menthone (–)-Menthone Thujone Piperitone (+)-Carvone (–)-Carvone Camphor (+)-Citronellol (–)-Citronellol (+)-Menthol (–)-Menthol	103534.8–1716498 μg/ml 858249–27463968 μg/ml 103534.8–6865992 μg/ml 12260.7–3432996 μg/ml 12260.7–1716498 μg/ml 223662.5–6787000 μg/ml 894650–14314400 μg/ml 919469.2–7355753.6 μg/ml 112650.2–3732679.6 μg/ml 114167.2–1892772 μg/ml 114167.2–1892772 μg/ml 246612.6–1978990 μg/ml 24680–208237.5 μg/ml 24680–208237.5 μg/ml 53128.4–3562728 μg/ml 53128.4–3562728 μg/ml	Iraji et al. 2020
Fungal pathogens
Candida glabrata	Thymol Carvacrol Eugenol (+)-α-Pinene (–)-α-Pinene β-Pinene (+)-Limonene (–)-Limonene (+)-Menthone (–)-Menthone Thujone Piperitone (+)-Carvone (–)-Carvone Camphor (+)-Citronellol (–)-Citronellol (+)-Menthol (–)-Menthol	390 μg/ml 62.50–195 μg/ml 1000–2000 μg/ml 51767.4–1716498 μg/ml 858249–54927936 μg/ml 103534.8–1716498 μg/ml 50405.1–3432996 μg/ml 50405.1–3432996 μg/ml 447325–7157200 μg/ml 1789300–14314400 μg/ml 1838938.4–14711507.2 μg/ml 232911.9–3732679.6 μg/ml 114167.2–3785544 μg/ml 114167.2–3785544 μg/ml 59369.7–989495 μg/ml 49360–208237.5 μg/ml 49360–208237.5 μg/ml 26564.2–445341 μg/ml 26564.2–445341 μg/ml	Sharifzadeh et al. 2019; Iraji et al. 2020; Biernasiuk et al. 2022; Stringaro et al. 2022
Candida krusei	Thymol Carvacrol Eugenol (+)-α-Pinene (–)-α-Pinene β-Pinene (+)-Limonene (–)-Limonene (+)-Menthone (–)-Menthone Thujone Piperitone (+)-Carvone (–)-Carvone Camphor (+)-Citronellol (–)-Citronellol (+)-Menthol (–)-Menthol	390 μg/ml 87.50–125 μg/ml 250–1000 μg/ml 51767.4–858249 μg/ml 858249–1716498 μg/ml 103534.8–429124.5 μg/ml 8173.8–6865992 μg/ml 8173.8–429124.5 μg/ml 447325–3578600 μg/ml 3578600–7157200 μg/ml 919469.2–7355753.6 μg/ml 112650.2–933169.9 μg/ml 114167.2–1892772 μg/ml 114167.2–1892772 μg/ml 246612.6–3957980 μg/ml 100262.5–832950 μg/ml 100262.5–1665900 μg/ml 100006.4–445341 μg/ml 53128.4–445341 μg/ml	Sharifzadeh et al. 2019; Iraji et al. 2020; Biernasiuk et al. 2022; Stringaro et al. 2022
Candida parapsilosis	Eugenol (+)-α-Pinene (–)-α-Pinene β-Pinene (+)-Limonene (–)-Limonene (+)-Menthone (–)-Menthone Thujone Piperitone (+)-Carvone (–)-Carvone Camphor (+)-Citronellol (–)-Citronellol (+)-Menthol (–)-Menthol	500–100 μg/ml 51767.4–429124.5 μg/ml 429124.5–1716498 μg/ml 213881.1–431849.1 μg/ml 50405.1–429124.5 μg/ml 50405.1–213881.1 μg/ml 107975–1789300 μg/ml 894650–14314400 μg/ml 3677876.8–14711507.2 μg/ml 479524.5–3732679.6 μg/ml 473193–7571088 μg/ml 473193–7571088 μg/ml 59369.7–1978990 μg/ml 49360–416475 μg/ml 49360–416475 μg/ml 53128.4–890682 μg/ml 53128.4–445341 μg/ml	Iraji et al. 2020; Biernasiuk et al. 2022
Fungal pathogens
Candida tropicalis	Thymol Carvacrol (+)-α-Pinene (–)-α-Pinene β-Pinene (+)-Limonene (–)-Limonene (+)-Menthone (–)-Menthone Thujone Piperitone (+)-Carvone (–)-Carvone Camphor (+)-Citronellol (–)-Citronellol (+)-Menthol (–)-Menthol	390 μg/ml 97.5 μg/ml 429124.5–1716498 μg/ml 6865992–27463968 μg/ml 103534.8–3432996 μg/ml 213881.1–3432996 μg/ml 213881.1–1716498 μg/ml 447325–1789300 μg/ml 1789300–14314400 μg/ml 919469.2–7355753.6 μg/ml 112650.2–3732679.6 μg/ml 114167.2–1892772 μg/ml 114167.2–1892772 μg/ml 246612.6–989495 μg/ml 24680–100262.5 μg/ml 24680–100262.5 μg/ml 100006.4–445341 μg/ml 100006.4–445341 μg/ml	Iraji et al. 2020; Stringaro et al. 2022

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DOI: https://doi.org/10.33073/pjm-2025-010 | Journal eISSN: 2544-4646 | Journal ISSN: 1733-1331

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Language: English

Page range: 1 - 18

Submitted on: Jul 12, 2024

Accepted on: Sep 16, 2024

Published on: Mar 7, 2025

Published by: Polish Society of Microbiologists

In partnership with: Paradigm Publishing Services

Publication frequency: 4 issues per year

Keywords:

antimicrobial resistance,

Related subjects:

Microbiology and virology

© 2025 Amanda Shen-Yee Kong, Swee-Hua Erin Lim, Wan-Hee Cheng, Mohd Hafis Yuswan, Ngai-Paing Tan, Kok-Song Lai, published by Polish Society of Microbiologists
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Volume 74 (2025): Issue 1 (March 2025)

Harnessing Monoterpenes and Monoterpenoids as Weapons against Antimicrobial Resistance

Figures & Tables

Fig. 1.

Fig. 2.

Table I

Table II

Paradigm

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