Skip to main content
SpringerLink
Log in

The Role of Essential Oils in the Inhibition of Efflux Pumps and Reversion of Bacterial Resistance to Antimicrobials

  • Review Article
  • Published:
Current Microbiology Aims and scope Submit manuscript

Abstract

Due to the deaths from infections caused by multidrug-resistant microorganisms worldwide, the World Health Organization considers antibiotic resistance to be a critical global public health problem. Bacterial resistance mechanisms are diverse and can be acquired through the overexpression of transmembrane proteins that are called efflux pumps, which act by expelling drugs from the intracellular environment, thereby preventing their action and contributing to the severity of infections. Efflux pumps are one of the main mechanisms of bacterial resistance, and it is important to identify new molecules that are capable of inhibiting the action of efflux pumps and circumvent the problem of resistance linked to the expression of these transmembrane proteins. The plants are promising candidates for obtaining biologically active substances, such as essential oils, with antimicrobial activity and inhibitors of efflux pumps, which can help in the resensitization of bacterial strains resistant to antibiotics. Therefore, this review aims to present the recently reported inhibitory activity of essential oils against bacterial pathogens that produce efflux pumps.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Fernando DM, Kumar A (2013) Resistance-nodulation-division multidrug efflux pumps in gram-negative bacteria: role in virulence. Antibiotics 2(1):163–181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Marti E et al (2014) The role of aquatic ecosystems as reservoirs of antibiotic resistance. Trends Microbiol 22(1):36–41

    Article  CAS  PubMed  Google Scholar 

  3. Rahman T et al (2017) Efflux drug transporters at the forefront of antimicrobial resistance. Eur Biophys J 46(7):647–653

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Prasch S et al (2019) Resistance modulatory and efflux-inhibitory activities of capsaicinoids and capsinoids. Bioorg Chem 82:378–384

    Article  CAS  PubMed  Google Scholar 

  5. Leonard AF et al (2015) Human recreational exposure to antibiotic resistant bacteria in coastal bathing waters. Environ Int 82:92–100

    Article  CAS  PubMed  Google Scholar 

  6. Yu Z et al (2020) The alarming antimicrobial resistance in ESKAPEE pathogens: can essential oils come to the rescue? Fitoterapia 140:104433

    Article  CAS  PubMed  Google Scholar 

  7. van Duin D, Paterson DL (2020) Multidrug-resistant bacteria in the community: an update. Infect Dis Clin N Am 34(4):709–722

    Article  Google Scholar 

  8. Astolfi A et al (2017) Pharmacophore-based repositioning of approved drugs as novel Staphylococcus aureus NorA efflux pump inhibitors. J Med Chem 60(4):1598–1604

    Article  CAS  PubMed  Google Scholar 

  9. Touani FK et al (2014) Antibiotic-potentiation activities of four Cameroonian dietary plants against multidrug-resistant Gram-negative bacteria expressing efflux pumps. BMC Complement Altern Med 14(1):1–8

    Article  Google Scholar 

  10. Rampioni G et al (2017) Effect of efflux pump inhibition on Pseudomonas aeruginosa transcriptome and virulence. Sci Rep 7(1):1–14

    Article  CAS  Google Scholar 

  11. Reza A et al (2019) Effectiveness of efflux pump inhibitors as biofilm disruptors and resistance breakers in gram-negative (ESKAPEE) bacteria. Antibiotics 8(4):229

    Article  CAS  PubMed Central  Google Scholar 

  12. Rao M et al (2018) Antimicrobial compounds of plant origin as efflux pump inhibitors: new avenues for controlling multidrug resistant pathogens. J Antimicrob Agents 4:1–6

    Google Scholar 

  13. Sharma A et al (2019) Efflux pump inhibitors for bacterial pathogens: from bench to bedside. Indian J Med Res 149(2):129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Burt S (2004) Essential oils: their antibacterial properties and potential applications in foods—a review. Int J Food Microbiol 94(3):223–253

    Article  CAS  PubMed  Google Scholar 

  15. Bakkali F, Averbeck S, Averbeck D, Idaomar M (2008) Biological effects of essential oils—a review. Food Chem Toxicol 46(2):446–475

    Article  CAS  PubMed  Google Scholar 

  16. Aparna V et al (2014) Identification of natural compound inhibitors for multidrug efflux pumps of Escherichia coli and Pseudomonas aeruginosa using in silico high-throughput virtual screening and in vitro validation. PloS one 9(7):e101840

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Mikulášová M et al (2016) Synergism between antibiotics and plant extracts or essential oils with efflux pump inhibitory activity in coping with multidrug-resistant staphylococci. Phytochem Rev 15(4):651–662

    Article  CAS  Google Scholar 

  18. Almeida RS et al (2020) GC-MS profile and enhancement of antibiotic activity by the essential oil of Ocotea odorífera and safrole: inhibition of Staphylococcus aureus efflux pumps. Antibiotics 9(5):247

    Article  CAS  PubMed Central  Google Scholar 

  19. Lamut A et al (2019) Efflux pump inhibitors of clinically relevant multidrug resistant bacteria. Med Res Rev 39(6):2460–2504

    Article  CAS  PubMed  Google Scholar 

  20. Puzari M, Chetia P (2017) RND efflux pump mediated antibiotic resistance in Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa: a major issue worldwide. World J Microbiol Biotechnol 33(2):24

    Article  PubMed  CAS  Google Scholar 

  21. Schindler BD, Kaatz GW (2016) Multidrug efflux pumps of Gram-positive bacteria. Drug Resist Updat 27:1–13

    Article  CAS  PubMed  Google Scholar 

  22. Dwivedi GR et al (2017) Efflux pumps: warheads of gram-negative bacteria and efflux pump inhibitors. In: Sinha RP, Richa (eds) New approaches in biological research. Nova Science Publishers, New York, pp 35–72

    Google Scholar 

  23. Piddock LJ (2006) Multidrug-resistance efflux pumps? Not just for resistance. Nat Rev Microbiol 4(8):629–636

    Article  CAS  PubMed  Google Scholar 

  24. Kabra R et al (2019) Efflux pumps and antimicrobial resistance: paradoxical components in systems genomics. Prog Biophys Mol Biol 141:15–24

    Article  CAS  PubMed  Google Scholar 

  25. Mahamoud A et al (2007) Antibiotic efflux pumps in Gram-negative bacteria: the inhibitor response strategy. J Antimicrob Chemother 59(6):1223–1229

    Article  CAS  PubMed  Google Scholar 

  26. Prasch S, Bucar F (2015) Plant derived inhibitors of bacterial efflux pumps: an update. Phytochem Rev 14(6):961–974

    Article  CAS  Google Scholar 

  27. Du D et al (2018) Multidrug efflux pumps: structure, function and regulation. Nat Rev Microbiol 16(9):523–539

    Article  CAS  PubMed  Google Scholar 

  28. Poole K (2004) Efflux-mediated multiresistance in Gram-negative bacteria. Clin Microbiol Infect 10(1):12–26

    Article  CAS  PubMed  Google Scholar 

  29. Kuroda T, Tsuchiya T (2009) Multidrug efflux transporters in the MATE family. Biochim Biophys Acta Proteins Proteomics 1794(5):763–768

    Article  CAS  Google Scholar 

  30. Poole K (2005) Efflux-mediated antimicrobial resistance. J Antimicrob Chemother 56(1):20–51

    Article  CAS  PubMed  Google Scholar 

  31. Costa SS et al (2013) Multidrug efflux pumps in Staphylococcus aureus: an update. Open Microbiol J 7:59

    Article  PubMed  PubMed Central  Google Scholar 

  32. Pagès JM, Amaral L (2009) Mechanisms of drug efflux and strategies to combat them: challenging the efflux pump of Gram-negative bacteria. Biochim Biophys Acta Proteins Proteomics 1794(5):826–833

    Article  CAS  Google Scholar 

  33. Marquez B (2005) Bacterial efflux systems and efflux pumps inhibitors. Biochimie 87(12):1137–1147

    Article  CAS  PubMed  Google Scholar 

  34. Harzallah HJ et al (2012) Chemical composition, antibacterial and antifungal properties of Tunisian Nigella sativa fixed oil. Afr J Microbiol Res 6(22):4675–4679

    CAS  Google Scholar 

  35. Akthar MS et al (2014) Antimicrobial activity of essential oils extracted from medicinal plants against the pathogenic microorganisms: a review. J Issues ISSN 2350:1588

    Google Scholar 

  36. Ruddaraju LK et al (2020) A review on anti-bacterials to combat resistance: from ancient era of plants and metals to present and future perspectives of green nano technological combinations. Asian J Pharm Sci 15(1):42–59

    Article  PubMed  Google Scholar 

  37. Jugreet BS et al (2020) Chemistry, bioactivities, mode of action and industrial applications of essential oils. Trends Food Sci Technol 101:89–105

    Article  CAS  Google Scholar 

  38. Prabuseenivasan S et al (2006) In vitro antibacterial activity of some plant essential oils. BMC Complement Altern Med 6(1):1–8

    Article  CAS  Google Scholar 

  39. Langeveld WT et al (2014) Synergy between essential oil components and antibiotics: a review. Crit Rev Microbiol 40(1):76–94

    Article  CAS  PubMed  Google Scholar 

  40. Coutinho HDM et al (2010) Enhancement of the norfloxacin antibiotic activity by gaseous contact with the essential oil of Croton zehntneri. J Young Pharm 2(4):362–364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Coutinho HD et al (2010) Use of aromatherapy associated with antibiotictherapy: modulation of the antibiotic activity by the essential oil of Zanthoxylum articulatum using gaseous contact. J Essent Oil-Bear Plants 13(6):670–675

    Article  CAS  Google Scholar 

  42. Jin J et al (2010) Farnesol, a potential efflux pump inhibitor in Mycobacterium smegmatis. Molecules 15(11):7750–7762

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Fadli M et al (2011) Essential oils from Moroccan plants as potential chemosensitisers restoring antibiotic activity in resistant Gram-negative bacteria. Int J Antimicrob Agents 38(4):325–330

    Article  CAS  PubMed  Google Scholar 

  44. Fadli M et al (2014) First evidence of antibacterial and synergistic effects of Thymus riatarum essential oil with conventional antibiotics. Ind Crops Prod 61:370–376

    Article  CAS  Google Scholar 

  45. Fadli M et al (2016) Artemisia herba-alba Asso and Cymbopogon citratus (DC.) Stapf essential oils and their capability to restore antibiotics efficacy. Ind Crops Prod 89:399–404

    Article  CAS  Google Scholar 

  46. Coêlho ML et al (2016) Inhibition of the NorA multi-drug transporter by oxygenated monoterpenes. Microb Pathog 99:173–177

    Article  PubMed  CAS  Google Scholar 

  47. Limaverde PW et al (2017) Inhibition of the TetK efflux-pump by the essential oil of Chenopodium ambrosioides L. and α-terpinene against Staphylococcus aureus IS-58. Food Chem Toxicol 109:957–961

    Article  CAS  PubMed  Google Scholar 

  48. Oliveira-Tintino CDM et al (2018) Inhibition of the essential oil from Chenopodium ambrosioides L. and α-terpinene on the NorA efflux-pump of Staphylococcus aureus. Food Chem 262:72–77

    Article  CAS  Google Scholar 

  49. de Medeiros VM et al (2017) Chemical composition and modulation of bacterial drug resistance of the essential oil from leaves of Croton grewioides. Microb Pathog 111:468–471

    Article  PubMed  CAS  Google Scholar 

  50. Miladi H et al (2017) Synergistic effect of eugenol, carvacrol, thymol, p-cymene and γ-terpinene on inhibition of drug resistance and biofilm formation of oral bacteria. Microb Pathog 112:156–163

    Article  CAS  PubMed  Google Scholar 

  51. Ghafari O et al (2018) Antibacterial and anti-PmrA activity of plant essential oils against fluoroquinolone-resistant Streptococcus pneumoniae clinical isolates. Lett Appl Microbiol 67(6):564–569

    Article  CAS  PubMed  Google Scholar 

  52. Islamieh DI et al (2020) Reduced efflux pumps expression of Pseudomonas Aeruginosa with Satureja khuzistanica essential oil. Iran J Med Sci 45(6):463

    Google Scholar 

  53. Mahmoudi H et al (2020) Detection of adeABC efllux pump encoding genes and antimicrobial effect of Mentha longifolia and Menthol on MICs of imipenem and ciprofloxacin in clinical isolates of Acinetobacter baumannii. BMC Complement Med Ther 20(1):1–7

    Article  Google Scholar 

  54. Pereira da Cruz R et al (2020) Effect of α-bisabolol and its β-cyclodextrin complex as TetK and NorA efflux pump inhibitors in Staphylococcus aureus strains. Antibiotics 9(1):28

    Article  PubMed Central  CAS  Google Scholar 

  55. Cirino ICS et al (2014) The essential oil from Origanum vulgare L. and its individual constituents carvacrol and thymol enhance the effect of tetracycline against Staphylococcus aureus. Chemotherapy 60(5–6):290–293

    Article  CAS  PubMed  Google Scholar 

  56. Oo T et al (2021) Inhibition of bacterial efflux pumps by crude extracts and essential oil from Myristica fragrans Houtt. (Nutmeg) seeds against methicillin-resistant Staphylococcus aureus. Molecules 26:4662

    Article  PubMed  PubMed Central  Google Scholar 

  57. Leal ALAB et al (2021) Chemical composition and potentiating action of Norfloxacin mediated by the essential oil of Piper caldense C.D.C. against Staphylococcus aureus strains overexpressing efflux pump genes. Arch Microbiol 203:4727–4736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Sewanu SO et al (2015) Antimicrobial and efflux pumps inhibitory activities of Eucalyptus grandis essential oil against respiratory tract infectious bacteria. J Med Plants Res 9(10):343–348

    Article  CAS  Google Scholar 

  59. Chovanová R et al (2015) The inhibition the Tet (K) efflux pump of tetracycline resistant Staphylococcus epidermidis by essential oils from three Salvia species. Lett Appl Microbiol 61(1):58–62

    Article  PubMed  CAS  Google Scholar 

  60. Saviuc C et al (2016) Rosmarinus officinalis essential oil and eucalyptol act as efflux pumps inhibitors and increase ciprofloxacin efficiency against Pseudomonas aeruginosa and Acinetobacter baumannii MDR strains. Rom Biotechnol Lett 21(4):11783

    Google Scholar 

  61. Miladi H et al (2017) Use of carvacrol, thymol, and eugenol for biofilm eradication and resistance modifying susceptibility of Salmonella enterica serovar Typhimurium strains to nalidixic acid. Microb Pathog 104:56–63

    Article  CAS  PubMed  Google Scholar 

  62. Alav I et al (2018) Role of bacterial efflux pumps in biofilm formation. J Antimicrob Chemother 73(8):2003–2020

    Article  CAS  PubMed  Google Scholar 

  63. Lira MC et al (2020) Efficacy of oregano and rosemary essential oils to affect morphology and membrane functions of non cultivable sessile cells of Salmonella enteritidis 86 in biofilms formed on stainless steel. J Appl Microbiol 128(2):376–386

    Article  CAS  PubMed  Google Scholar 

  64. El-Tarabily KA et al (2021) Using essencial oils to overcome bacterial biofilm formation and their antimicrobial resistance. Saudi J Biol Sci. https://doi.org/10.1016/j.sjbs.2021.05.033

    Article  PubMed  PubMed Central  Google Scholar 

  65. Subhadra B et al (2018) Local repressor AcrR regulates AcrAB efflux pump required for biofilm formation and virulence in Acinetobacter nosocomialis. Front Cell Infect Microbiol 8:270

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Wang J et al (2019) Baicalin inhibits biofilm formation and the quorum-sensing system by regulating the MsrA drug efflux pump in Staphylococcus saprophyticus. Front Microbiol 10:2800

    Article  PubMed  PubMed Central  Google Scholar 

  67. Sharifi A et al (2021) Cuminum cyminum L. essential oil: a promising antibacterial and antivirulence agente against muldidrug-resistant Staphylococcus aureus. Front Microbiol 12:667833

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Maria Anndressa Alves Agreles thanks the Foundation for the Support of Science and Technology of the State of Pernambuco (FACEPE) for the Scientific Initiation scholarship (PIBIC).

Funding

No funding was received.

Author information

Authors and Affiliations

  1. Laboratory of Immunopathology Keizo Asami (LIKA), Federal University of Pernambuco (UFPE), Av. Prof. Moraes Rego, 1235, Cidade Universitária, Recife, Pernambuco, CEP: 50670-901, Brazil

    Maria Anndressa Alves Agreles, Iago Dillion Lima Cavalcanti & Isabella Macário Ferro Cavalcanti

  2. Laboratory of Microbiology and Immunology, Academic Center of Vitória (CAV), Federal University of Pernambuco (UFPE), Rua do Alto do Reservatório s/n, Bela Vista, Vitória de Santo Antão, Pernambuco, CEP: 55608-680, Brazil

    Isabella Macário Ferro Cavalcanti

Authors
  1. Maria Anndressa Alves Agreles
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Iago Dillion Lima Cavalcanti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Isabella Macário Ferro Cavalcanti
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MAAA: participated in all stages from study design of the review to the final version of the article. IDLC: participated in the writing of the article and review of the final version. IMFC: participated in all stages from study design of the review to the final version of the article.

Corresponding author

Correspondence to Isabella Macário Ferro Cavalcanti.

Ethics declarations

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Agreles, M.A.A., Cavalcanti, I.D.L. & Cavalcanti, I.M.F. The Role of Essential Oils in the Inhibition of Efflux Pumps and Reversion of Bacterial Resistance to Antimicrobials. Curr Microbiol 78, 3609–3619 (2021). https://doi.org/10.1007/s00284-021-02635-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00284-021-02635-1

Search

Navigation