Harnessing Monoterpenes and Monoterpenoids as Weapons against Antimicrobial Resistance

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

doi:10.33073/pjm-2025-010

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

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

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.	ThymolCarvacrolGeraniolLimoneneEugenolCinnamaldehyde	200–450 μg/ml100–450 μg/ml100–350 μg/ml100–450 μg/ml200–450 μg/ml10–50 μg/ml	Caballero Gómez et al. 2022
Vancomycin-sensitive Enterococcus (VSE)	CarvacrolCuminaldehydeLinaloolp-Cymeneγ-Terpinene	593.37 μg/ml19919562 μg/ml35199850 μg/ml8599475.4 μg/ml17060082.9 μg/ml	Owen et al. 2019
Vancomycin-resistant Enterococcus (VRE)	CarvacrolCuminaldehydeLinaloolp-Cymeneγ-Terpinene	593369 μg/ml79679730 μg/ml8799962.5 μg/ml8599475.4 μg/ml17060082.9 μg/ml	Owen et al. 2019
Staphylococcus sp.	ThymolCarvacrolGeraniolLimoneneEugenolCinnamaldehyde	200–400 μg/ml200–400 μg/ml100–400 μg/ml100–400 μg/ml300–400 μg/ml10–50 μg/ml	Caballero Gómez et al. 2022
Staphylococcus aureus	ThymolCarvacrolLimoneneα-Pineneβ-Pinenep-Cymene1,8-CineoleLimoneneFenchoneLinaloolCamphorcis-VerbenolBorneolTerpinen-4-olVerbenoneCarvoneEugenolLinalyl acetatetrans-AnetholeMenthone	72–800 μg/ml256–3200 μg/ml0.048 μg/ml11.88 μg/ml10.13 μg/ml10.25 μg/ml5.63–115100 μg/ml2.63 μg/ml4.25 μg/ml2.88–6800 μg/ml7.63 μg/ml2.38 μg/ml3.75 μg/ml3.13 μg/ml5.88 μg/ml11.38 μg/ml24–11100 μg/ml46900 μg/ml494000 μg/ml27900 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	CarvacrolCuminaldehydeLinaloolp-Cymeneγ-Terpinene	297435.6 μg/ml4979520 μg/ml17599925 μg/ml1075102.2 μg/ml8529360.3 μg/ml	Owen et al. 2019
Methicillin-resistant Staphylococcus aureus	CarvacrolCuminaldehydeLinaloolp-Cymeneγ-Terpinene	148717.8 μg/ml9960522 μg/ml8799962.5 μg/ml2150204.4 μg/ml17060082.9 μg/ml	Owen et al. 2019
Mupirocin-susceptible Staphylococcus aureus	1,8-cineoleEugenolCarvacrolLinalool(–)-MenthoneLinalyl acetatetrans-Anethole	307000 μg/ml2080 μg/ml950 μg/ml6800 μg/ml27910 μg/ml450500 μg/ml494000 μg/ml	Kwiatkowski et al. 2019
Mupirocin-resistant Staphylococcus aureus	1,8-cineoleEugenolCarvacrolLinalool(–)-MenthoneLinalyl acetatetrans-Anethole	57560 μg/ml8340 μg/ml480 μg/ml2830 μg/ml6980 μg/ml450500 μg/ml494000 μg/ml	Kwiatkowski et al. 2019
Staphylococcus pseudintermedius	ThymolCarvacrol	100–200 μg/ml146–292 μg/ml	Sim et al. 2019
β-haemolytic Streptococcus spp.	ThymolCarvacrol	200–400 μg/ml146–292 μg/ml	Sim et al. 2019
Streptococcus suis	CinnamaldehydeCarvacrolThymol	156.25–312.5 μg/ml156.25 μg/ml156.25 μg/ml	de Aguiar et al. 2019
Gram-negative bacteria
Acinetobacter baumannii	α-PineneCampheneβ-Pinened-3-Carenep-Cymene1,8-CineoleLimoneneγ-TerpineneFenchoneLinaloolCamphorcis-VerbenolBorneolTerpinen-4-olVerbenoneCarvone	11.88 μg/ml20.00 μg/ml13.50 μg/ml7.88 μg/ml5.13 μg/ml5.63 μg/ml5.25 μg/ml4.88 μg/ml1.06 μg/ml1.44 μg/ml10.17 μg/ml9.50 μg/ml0.94 μg/ml0.78 μg/ml4.70 μg/ml7.58 μg/ml	Sayout et al. 2020
Campylobacter jejuni	ThymolCarvacrolThymoquinonep-Cymeneγ-Terpinene	31.25 μg/ml31.25 μg/ml31.25 μg/ml1000 μg/ml1000 μg/ml	Šimunović et al. 2020
Enterobacter aerogenes	β-Pinene1,8-CineoleLimoneneγ–TerpineneFenchoneLinaloolCamphorcis-VerbenolBorneolVerbenoneCarvone	20.25 μg/ml2.81 μg/ml1.31 μg/ml4.88 μg/ml2.13 μg/ml1.44 μg/ml15.25 μg/ml2.38 μg/ml0.94 μg/ml2.94 μg/ml5.69 μg/ml	Sayout et al. 2020
Enterobacter cloacae	α-Pineneβ-PineneMyrcened-3-Carenep-Cymene1,8-CineoleLimoneneγ-TerpineneFenchoneLinaloolCamphorcis-VerbenolBorneolTerpinen-4-olVerbenoneCarvone	11.88 μg/ml5.06 μg/ml7.75 μg/ml7.88 μg/ml4.10 μg/ml5.63 μg/ml2.63 μg/ml6.50 μg/ml1.70 μg/ml1.92 μg/ml6.10 μg/ml3.17 μg/ml1.50 μg/ml3.13 μg/ml3.36 μg/ml9.10 μg/ml	Sayout et al. 2020
Ciprofloxacin-resistant Escherichia coli	CarvacrolCuminaldehydeLinaloolp-Cymeneγ-Terpinene	297435.6 μg/ml1244880 μg/ml8799962.5 μg/ml1075102.2 μg/ml34120165.8 μg/ml	Owen et al. 2019
Escherichia coli	CarvacrolCuminaldehydeLinaloolp-Cymeneγ-TerpineneLimoneneα-PineneCampheneβ-PineneMyrcened-3-Carenep-Cymene1,8-CineoleLimoneneγ-TerpineneFenchoneLinaloolCamphorcis-VerbenolBorneolTerpinen-4-olVerbenoneCarvone	297435.6 μg/ml311220 μg/ml8799962.5 μg/ml2150204.4 μg/ml34120165.8 μg/ml0.048 μg/ml11.88 μg/ml15.00 μg/ml5.06 μg/ml1.94 μg/ml7.88 μg/ml2.56 μg/ml2.81 μg/ml2.63 μg/ml4.88 μg/ml4.25 μg/ml2.88 μg/ml7.63 μg/ml4.75 μg/ml3.75 μg/ml3.13 μg/ml5.88 μg/ml11.38 μg/ml	Owen et al. 2019; Sayout et al. 2020; Noumi et al. 2023
Klebsiella oxytoca	β-Pinene1,8-CineoleLimoneneγ-TerpineneFenchoneLinaloolCamphorcis-VerbenolBorneolTerpinen-4-olVerbenoneCarvone	13.50 μg/ml5.63 μg/ml2.63 μg/ml4.88 μg/ml2.13 μg/ml1.44 μg/ml10.17 μg/ml3.17 μg/ml2.5 μg/ml6.25 μg/ml5.88 μg/ml11.38 μg/ml	Sayout et al. 2020
Klebsiella pneumoniae	ThymolCarvacrolGeraniolα-PineneCampheneβ-PineneMyrcened-3-Carenep-Cymene1,8-CineoleLimoneneγ-TerpineneFenchoneLinaloolCamphorcis-VerbenolBorneolTerpinen-4-olVerbenoneCarvone	780 μg/ml130–1910 μg/ml1740 μg/ml23.75 μg/ml30.00 μg/ml10.13 μg/ml15.50 μg/ml7.88 μg/ml10.25 μg/ml11.25 μg/ml2.63 μg/ml4.88 μg/ml2.13 μg/ml3.83 μg/ml5.08 μg/ml2.38 μg/ml0.47 μg/ml1.56 μg/ml3.36 μg/ml15.17 μg/ml	Sayout et al. 2020;de Souza et al. 2021;Kwiatkowski et al. 2022
Malassezia pachydermatis	ThymolCarvacrolCinnamaldehyde	10–800 μg/ml10–585 μg/ml2.5–640 μg/ml	Schlemmer et al. 2019;Sim et al. 2019
Salmonella enterica	Limonene	0.048 μg/ml	Noumi et al. 2023
Salmonella spp.	β-Pinene1,8-CineoleLimoneneγ-TerpineneFenchoneLinaloolCamphorcis-VerbenolTerpinen-4-olVerbenoneCarvone	8.10 μg/ml7.50 μg/ml2.63 μg/ml6.50 μg/ml1.70 μg/ml2.88 μg/ml6.10 μg/ml1.90 μg/ml3.13 μg/ml3.92 μg/ml22.75 μg/ml	Sayout et al. 2020
Shigella flexeneri	Limonene	0.048 μg/ml	Noumi et al. 2023
Proteus mirabilis	ThymolCarvacrol	200 μg/ml146–292 μg/ml	Sim et al. 2019
Pseudomonas sp.	ThymolCarvacrolGeraniolLimoneneEugenolCinnamaldehyde	100–300 μg/ml100–400 μg/ml100–400 μg/ml100–300 μg/ml300–400 μg/ml10–50 μg/ml	Caballero Gómez et al. 2022
Ciprofloxacin-resistant Pseudomonas aeruginosa	CarvacrolCuminaldehydeLinaloolp-Cymeneγ-Terpinene	4749956.4 μg/ml39840606 μg/ml140799400 μg/ml8599475.4 μg/ml34120165.8 μg/ml	Owen et al. 2019
Pseudomonas aeruginosa	ThymolCarvacrolCuminaldehydeLinaloolp-Cymeneγ-TerpineneLimoneneβ-Pinene	400–800 μg/ml585–1120 μg/ml39839124 μg/ml35199850 μg/ml8599475.4 μg/ml68240331.6 μg/ml0.048 μg/ml10.13 μg/ml	Owen et al. 2019;Sim et al. 2019;Noumi et al. 2023
Pseudomonas aeruginosa	LimoneneFenchoneLinaloolCamphorcis-VerbenolBorneolTerpinen-4-olVerbenoneCarvone	2.63 μg/ml1.70 μg/ml1.92 μg/ml6.10 μg/ml1.58 μg/ml1.88 μg/ml3.13 μg/ml4.70 μg/ml9.10 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	ThymolCarvacrolEugenolGeraniolCinnamaldehyde	282413.6 μg/ml282413.6 μg/ml308696 μg/ml1156875 μg/ml555750 μg/ml	Rossi et al. 2021
Vibrio harveyi	ThymolCarvacrolEugenolGeraniolCinnamaldehyde	141206.8 μg/ml141206.8 μg/ml308696 μg/ml1156875 μg/ml278616 μg/ml	Rossi et al. 2021
Fungal pathogens
Candida albicans	ThymolCarvacrolEugenolMethyl eugenol(+)-α-Pinene(–)-α-Pineneβ-Pinene(+)-Limonene(–)-Limonene(+)-Menthone(–)-MenthoneThujonePiperitone(+)-Carvone(–)-CarvoneCamphor(+)-Citronellol(–)-Citronellol(+)-Menthol(–)-Menthol	195–625 μg/ml43.75–250 μg/ml500–2000 μg/ml1250 μg/ml51767.4–1716498 μg/ml858249–54927936 μg/ml213881.1–13731984 μg/ml8173.8–6865992 μg/ml8173.8–13731984 μg/ml3578600–6787000 μg/ml1789300–28628800 μg/ml459734.6–7355753.6 μg/ml239762.25–3732679.6 μg/ml473193–3785544 μg/ml473193–3785544 μg/ml494747.5–3957980 μg/ml49360–1665900 μg/ml49360–1665900 μg/ml221889.2–7125456 μg/ml221889.2–7125456 μg/ml	Sharifzadeh et al. 2019;Iraji et al. 2020;Shaban et al. 2020;Stringaro et al. 2022;Biernasiuk et al. 2022
Candida auris	CarvacrolThymolEugenolMethyl eugenol	125 μg/ml312 μg/ml625 μg/ml1250 μg/ml	Shaban et al. 2020
Candida dubliniensis	(+)-α-Pinene(–)-α-Pineneβ-Pinene(+)-Limonene(–)-Limonene(+)-Menthone(–)-MenthoneThujonePiperitone(+)-Carvone(–)-CarvoneCamphor(+)-Citronellol(–)-Citronellol(+)-Menthol(–)-Menthol	103534.8–1716498 μg/ml858249–27463968 μg/ml103534.8–6865992 μg/ml12260.7–3432996 μg/ml12260.7–1716498 μg/ml223662.5–6787000 μg/ml894650–14314400 μg/ml919469.2–7355753.6 μg/ml112650.2–3732679.6 μg/ml114167.2–1892772 μg/ml114167.2–1892772 μg/ml246612.6–1978990 μg/ml24680–208237.5 μg/ml24680–208237.5 μg/ml53128.4–3562728 μg/ml53128.4–3562728 μg/ml	Iraji et al. 2020
Fungal pathogens
Candida glabrata	ThymolCarvacrolEugenol(+)-α-Pinene(–)-α-Pineneβ-Pinene(+)-Limonene(–)-Limonene(+)-Menthone(–)-MenthoneThujonePiperitone(+)-Carvone(–)-CarvoneCamphor(+)-Citronellol(–)-Citronellol(+)-Menthol(–)-Menthol	390 μg/ml62.50–195 μg/ml1000–2000 μg/ml51767.4–1716498 μg/ml858249–54927936 μg/ml103534.8–1716498 μg/ml50405.1–3432996 μg/ml50405.1–3432996 μg/ml447325–7157200 μg/ml1789300–14314400 μg/ml1838938.4–14711507.2 μg/ml232911.9–3732679.6 μg/ml114167.2–3785544 μg/ml114167.2–3785544 μg/ml59369.7–989495 μg/ml49360–208237.5 μg/ml49360–208237.5 μg/ml26564.2–445341 μg/ml26564.2–445341 μg/ml	Sharifzadeh et al. 2019;Iraji et al. 2020;Biernasiuk et al. 2022;Stringaro et al. 2022
Candida krusei	ThymolCarvacrolEugenol(+)-α-Pinene(–)-α-Pineneβ-Pinene(+)-Limonene(–)-Limonene(+)-Menthone(–)-MenthoneThujonePiperitone(+)-Carvone(–)-CarvoneCamphor(+)-Citronellol(–)-Citronellol(+)-Menthol(–)-Menthol	390 μg/ml87.50–125 μg/ml250–1000 μg/ml51767.4–858249 μg/ml858249–1716498 μg/ml103534.8–429124.5 μg/ml8173.8–6865992 μg/ml8173.8–429124.5 μg/ml447325–3578600 μg/ml3578600–7157200 μg/ml919469.2–7355753.6 μg/ml112650.2–933169.9 μg/ml114167.2–1892772 μg/ml114167.2–1892772 μg/ml246612.6–3957980 μg/ml100262.5–832950 μg/ml100262.5–1665900 μg/ml100006.4–445341 μg/ml53128.4–445341 μg/ml	Sharifzadeh et al. 2019;Iraji et al. 2020;Biernasiuk et al. 2022;Stringaro et al. 2022
Candida parapsilosis	Eugenol(+)-α-Pinene(–)-α-Pineneβ-Pinene(+)-Limonene(–)-Limonene(+)-Menthone(–)-MenthoneThujonePiperitone(+)-Carvone(–)-CarvoneCamphor(+)-Citronellol(–)-Citronellol(+)-Menthol(–)-Menthol	500–100 μg/ml51767.4–429124.5 μg/ml429124.5–1716498 μg/ml213881.1–431849.1 μg/ml50405.1–429124.5 μg/ml50405.1–213881.1 μg/ml107975–1789300 μg/ml894650–14314400 μg/ml3677876.8–14711507.2 μg/ml479524.5–3732679.6 μg/ml473193–7571088 μg/ml473193–7571088 μg/ml59369.7–1978990 μg/ml49360–416475 μg/ml49360–416475 μg/ml53128.4–890682 μg/ml53128.4–445341 μg/ml	Iraji et al. 2020;Biernasiuk et al. 2022
Fungal pathogens
Candida tropicalis	ThymolCarvacrol(+)-α-Pinene(–)-α-Pineneβ-Pinene(+)-Limonene(–)-Limonene(+)-Menthone(–)-MenthoneThujonePiperitone(+)-Carvone(–)-CarvoneCamphor(+)-Citronellol(–)-Citronellol(+)-Menthol(–)-Menthol	390 μg/ml97.5 μg/ml429124.5–1716498 μg/ml6865992–27463968 μg/ml103534.8–3432996 μg/ml213881.1–3432996 μg/ml213881.1–1716498 μg/ml447325–1789300 μg/ml1789300–14314400 μg/ml919469.2–7355753.6 μg/ml112650.2–3732679.6 μg/ml114167.2–1892772 μg/ml114167.2–1892772 μg/ml246612.6–989495 μg/ml24680–100262.5 μg/ml24680–100262.5 μg/ml100006.4–445341 μg/ml100006.4–445341 μg/ml	Iraji et al. 2020;Stringaro et al. 2022

Harnessing Monoterpenes and Monoterpenoids as Weapons against Antimicrobial Resistance

Figures & Tables

Fig. 1.

Fig. 2.

Mechanism of action of monoterpenes against tested pathogens_

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

Paradigm

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