Zeitschrift für Phytotherapie 2021; 42(05): 233-240
DOI: 10.1055/a-1584-5376
Peer Review

Ätherische Öle aus Zimt und Gewürznelken verstärken die Wirkung von Antibiotika gegen multiresistente bakterielle Krankheitserreger

Essential Oils from Cinnamon and Clove Enhance the Effects of Antibiotics Against Multi-drug-resistant Pathogens
Hana Sakr
1   Institut für Pharmazie, Freie Universität Berlin, Berlin
,
Sebastian Schmidt
2   Hofmann & Sommer GmbH u. Co. KG, Berlin
,
Stefan Bereswill
3   Institut für Mikrobiologie und Infektionsimmunologie, Charité – Universitätsmedizin Berlin, Berlin
,
Markus M. Heimesaat
3   Institut für Mikrobiologie und Infektionsimmunologie, Charité – Universitätsmedizin Berlin, Berlin
,
Matthias F. Melzig
1   Institut für Pharmazie, Freie Universität Berlin, Berlin
› Author Affiliations
Förderung durch Dritte Diese Arbeit wurde im Rahmen von Drittmittelprojekten vom Bundesministerium für Bildung und Forschung (PAC-Campylobacter IP7/01KI1725D) und laut Beschluss des Deutschen Bundestags vom Bundesministerium für Wirtschaft und Energie (ZIM, ZF4117908 AJ8) gefördert.

Zusammenfassung

Die Häufigkeit bakterieller Infektionen, bei denen Antibiotika nicht mehr wirken, steigt aufgrund der Resistenzentwicklung der Krankheitserreger weltweit. Um dieser Bedrohung zu begegnen, werden – neben der Entwicklung neuer Antibiotika und der Reaktivierung bereits vorhandener antibakterieller Wirkstoffe – auch die Resistenz-modifizierenden Eigenschaften von Naturstoffen erforscht. In der vorliegenden Arbeit wurde mit dem Checkerboard-Mikrodilutionsverfahren untersucht, wie die ätherischen Öle aus Gewürznelken (Syzygium aromaticum) und der Rinde des Zimtbaums (Cinnamomum verum) kombiniert mit Lysozym die Wirkungen von Antibiotika aus der Gruppe der Carbapeneme (Imipenem) und der Aminoglykoside (Gentamicin) gegen die bakteriellen Krankheitserreger Pseudomonas aeruginosa bzw. Klebsiella pneumoniae verstärken. Die Ergebnisse zeigen, dass die ätherischen Öle beider Pflanzenarten die minimalen Hemmkonzentrationen von Gentamicin und Imipenem gegenüber multiresistenten klinischen Isolaten der beiden gramnegativen Bakterienarten vermindern und damit die Antibiotikawirkung signifikant steigern. Die potenten Resistenz-modifizierenden Eigenschaften der ätherischen Öle lassen weitere Untersuchungen der Phenylpropanoide als Hauptkomponenten beider Öle und anderer Naturstoffe in diesem Kontext vielversprechend erscheinen.

Abstract

The frequency of bacterial infections for which antibiotics no longer work is increasing worldwide due to the development of antibiotic resistance among pathogens. Research topics, in order to counter this threat, include the development of new antibiotics, the reactivation of existing antibacterial agents and the finding of resistance-modifying properties of natural substances. In the present work, the checkerboard microdilution method was used to investigate how the essential oils from cloves (Syzygium aromaticum) and cinnamon (Cinnamomum verum) combined with lysozyme amplify the effects of a carbapenem- (imipenem) and an aminoglycoside-antibiotic (gentamicin) against the bacterial pathogens Pseudomonas aeruginosa and Klebsiella pneumoniae. The results indicate that the essential oils of both plant species reduce the minimum inhibitory concentrations of gentamicin and imipenem against multi-drug resistant clinical isolates of the two gram-negative bacterial species and thus significantly increase the antibiotic effects. The observed potent resistance-modifying properties of the essential oils favour further investigations of the phenylpropanoids as the main components of both oils and other natural substances in this context.



Publication History

Received: 11 August 2021

Accepted after revision: 20 September 2021

Article published online:
25 October 2021

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  • Literatur

  • 1 Bassolé IHN, Lamien-Meda A, Bayala B. et al Composition and antimicrobial activities of Lippia multiflora Moldenke, Mentha x piperita L. and Ocimum basilicum L. essential oils and their major monoterpene alcohols alone and in combination. Molecules 2010; 15: 7825-7839
  • 2 Chellat MF, Raguž L, Riedl R. Antibiotikaresistenzen gezielt überwinden. Angewandte Chemie 2016; 128: 6710-6738
  • 3 Chung PY. The emerging problems of Klebsiella pneumoniae infections: carbapenem resistance and biofilm formation. FEMS Microbiol Lett 2016; 363: 1-6
  • 4 Clinical and Laboratory Standards Institute: Methods for Dilution Antimicrobial Susceptibility Tests for Bacterial that Grow Aerobically. 9th ed., Approved Standard M07-A9. 32(2). CLSI; Wayne, PA:
  • 5 Cox SD, Mann CM, Markham JL. et al Determining the antimicrobial actions of tea tree oil. Molecules 2001; 6: 87-91
  • 6 Driscoll JA, Brody SL, Kollef MH. The epidemiology, pathogenesis and treatment of Pseudomonas aeruginosa infections. Drugs 2007; 67: 351-368
  • 7 El Atki Y, Aouam I, El Kamari F. et al Antibacterial activity of cinnamon essential oils and their synergistic potential with antibiotics. J Adv Pharm Technol Res 2019; 10: 63-67
  • 8 Hemaiswarya S, Doble M. Synergistic interaction of eugenol with antibiotics against Gram negative bacteria. Phytomedicine 2009; 16: 997-1005
  • 9 Hyldgaard M, Mygind T, Meyer RL. Essential oils in food preservation: mode of action, synergies, and interactions with food matrix components. Front Microbiol 2012; 3: 320-329
  • 10 Lee CR, Lee JH, Park KS. et al Global dissemination of Carbapenemase-producing Klebsiella pneumoniae: epidemiology, genetic context, treatment options, and detection methods. Front Microbiol 2016; 7: 895
  • 11 Liu Q, Niu H, Zhang W. et al Synergy among thymol, eugenol, berberine, cinnamaldehyde and streptomycin against planktonic and biofilm-associated food-borne pathogens. Lett Appl Microbiol 2015; 60: 421-430
  • 12 Martin NL, Beveridge TJ. Gentamicin interaction with Pseudomonas aeruginosa cell envelope. Antimicrob Agents Chemother 1986; 29: 1079-1087
  • 13 Masuda N, Sakagawa E, Ohya S. et al Contribution of the MexX-MexY-oprM efflux system to intrinsic resistance in Pseudomonas aeruginosa . Antimicrob Agents Chemother 2000; 44: 2242-2246
  • 14 Moon SE, Kim HY, Cha JD. Synergistic effect between clove oil and its major compounds and antibiotics against oral bacteria. Arch Oral Biol 2011; 56: 907-916
  • 15 Mutschler E, Geisslinger G, Kroemer HK. et al Mutschler Arzneimittelwirkungen. 10. Aufl Stuttgart: Wiss. Verlagsges; 2012
  • 16 Navon-Venezia S, Kondratyeva K, Carattoli A. Klebsiella pneumoniae: a major worldwide source and shuttle for antibiotic resistance. FEMS Microbiol Rev 2017; 41: 252-275
  • 17 Nuñez L, Aquino MD. Microbicide activity of clove essential oil (Eugenia caryophyllata). Braz J Microbiol 2012; 43: 1255-1260
  • 18 Pang Z, Raudonis R, Glick BR. et al Antibiotic resistance in Pseudomonas aeruginosa: mechanisms and alternative therapeutic strategies. Biotechnol Adv 2018; 37: 177-192
  • 19 Pfeiffer Y. ESBL, AmpC und Carbapenemasen: Vorkommen, Verbreitung und Diagnostik β-Lactamase-bildender Gram-negativer Krankheitserreger. LaboratoriumsMedizin 2010; 34: 205-215 DOI: 10.1515/jlm.2010.042.
  • 20 Podschun R, Ullmann U. Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors. Clin Microbiol Rev 1998; 11: 589-603
  • 21 Qian W, Sun Z, Wang T. et al Antimicrobial activity of eugenol against carbapenem-resistant Klebsiella pneumoniae and its effect on biofilms. Microb Pathog 2019; 139: 2-8
  • 22 Robert Koch-Institut. Epid Bull Nr. 9/2019: 81–88 https://www.rki.de/DE/Content/Infekt/EpidBull/Archiv/2019/Ausgaben/09_19.pdf?__blob=publicationFile
  • 23 Rojo L, Vazquez B, Parra J. et al From natural products to polymeric derivatives of “eugenol”: a new approach for preparation of dental composites and orthopedic bone cements. Biomacromolecules 2006; 7: 2751-2761
  • 24 Rosenberg CR, Fang X, Allison KR. Potentiating aminoglycoside antibiotics to reduce their toxic side effects. PLoS One 2020; 15: 1-17
  • 25 Saito H, Sakakibara Y, Sakata A. et al Antibacterial activity of lysozyme-chitosan oligosaccharide conjugates (LYZOX) against Pseudomonas aeruginosa, Acinetobacter baumannii and Methicillin-resistant Staphylococcus aureus . PLoS One 2019; 14: 1-26
  • 26 Sakr H. Modifikation der Antibiotikaresistenzen klinisch relevanter Gram-negativer bakterieller Krankheitserreger durch Lysozym in Kombination mit ätherischen Ölen [Diplomarbeit]. Universität Greifswald, Institut für Pharmazie 2021; 50-53
  • 27 Shen S, Zhang T, Yuan Y. et al Effects of cinnamaldehyde on Escherichia coli and Staphylococcus aureus membrane. Food Control 2015; 47: 196-202
  • 28 Tan X, Kim HS, Baugh K. et al Therapeutic options for metallo-β-lactamase-producing Enterobacterales. Infect Drug Resist 2021; 14: 125-142
  • 29 Tarek N, Hassan HM, Abdel-Ghani SM. et al Comparative chemical and antimicrobial study of nine essential oils obtained from medicinal plants growing in Egypt. BJBAS 2014; 3: 149-156
  • 30 Tétard A, Zedet A, Girard C. et al Cinnamaldehyde induces expression of efflux pumps and multidrug resistance in Pseudomonas aeruginosa . Antimicrob Agents Chemother 2019; 63: e01081-19
  • 31 Teuscher E, Melzig MF, Lindequist U. Biogene Arzneimittel. 7. Aufl Stuttgart: Wiss. Verlagsges; 2012
  • 32 The European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters. Version 11.0, 2021
  • 33 Tsai YK, Fung CP, Lin JC. et al Klebsiella pneumoniae outer membrane porins OmpK35 and OmpK36 play roles in both antimicrobial resistance and virulence. Antimicrob Agents Chemother 2011; 55: 1485-1493
  • 34 Utchariyakiat I, Surassmo S, Jaturanpinyo M. et al Efficacy of cinnamon bark oil and cinnamaldehyde on anti-multidrug resistant Pseudomonas aeruginosa and the synergistic effects in combination with other antimicrobial agents. BMC Complement Altern Med 2016; 16: 158
  • 35 Vasconcelos NG, Croda J, Simionatto S. Antibacterial mechanisms of cinnamon and its constituents: A review. Microb Pathog 2018; 120: 198-203
  • 36 Wiegand I, Hilpert K, Hancock RE. Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nature Protocols 2008; 3: 163-175
  • 37 Wild P, Gabrieli A, Schraner EM. et al Reevaluation of the effect of lysoyzme on Escherichia coli employing ultrarapid freezing followed by cryoelectronmicroscopy or freeze substitution. Microsc Res Tech 1997; 39: 297-304
  • 38 World Health Organization. Global action plan on antimicrobial resistance. 2015 https://www.who.int/publications/i/item/9789241509763
  • 39 Wright GD. Antibiotic adjuvants: rescuing antibiotics from resistance. Trends Microbiol 2016; 24: 862-871
  • 40 Xu Y, Yin Y, Li T. et al Effects of lysozyme combined with cinnamaldehyde on storage quality of olive flounder (Paralichthys olivaceus) fillets. J Food Sci 2020; 85: 1037-1044
  • 41 Yan L, Zhang L, Yang H. et al In vitro synergism testing of three antimicrobial agents against multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis by checkerboard method. J Mol Pharm Org Process Res 2015; 3: 123 DOI: 10.4172/2329-9053.1000123.
  • 42 Yang SK, Yusoff K, Ajat M. et al Disruption of KPC-producing Klebsiella pneumoniae membrane via induction of oxidative stress by cinnamon bark (Cinnamomum verum J. Presl) essential oil. PLoS One 2019; 14: 1-20
  • 43 Zhanel GG, Simor AE, Vercaigne L. et al Canadian Carbapenem Discussion Group. Imipenem and meropenem: Comparison of in vitro activity, pharmacokinetics, clinical trials and adverse effects. Can J Infect Dis 1998; 9: 215-228