nach oben

European Journal of Clinical Microbiology & Infectious Diseases

Erschienen in:

15.01.2016 | Original Article

The licorice pentacyclic triterpenoid component 18β-glycyrrhetinic acid enhances the activity of antibiotics against strains of methicillin-resistant Staphylococcus aureus

verfasst von: A. de Breij, T. G. Karnaoukh, J. Schrumpf, P. S. Hiemstra, P. H. Nibbering, J. T. van Dissel, P. C. de Visser

Erschienen in: European Journal of Clinical Microbiology & Infectious Diseases | Ausgabe 4/2016

Einloggen, um Zugang zu erhalten

Abstract

This study aimed to identify compounds that enhance the activity of current antibiotics against multidrug-resistant bacteria. Screening of a 350+ compound proprietary small molecules library revealed that the Glycyrrhiza glabra (licorice)-derived triterpenoid 18β-glycyrrhetinic acid (18β-GA) potentiated the antibacterial activity of certain antibiotics against Staphylococcus aureus. Here, we evaluated the ability of pentacyclic triterpenoids to potentiate the activity of antibiotics against strains of methicillin-resistant S. aureus (MRSA). Checkerboard assays were used to assess the minimum inhibitory concentration (MIC) of tobramycin and ten pentacyclic triterpenoids against S. aureus. The effect of 18β-GA on the MIC of different antibiotics against MRSA was also determined in an in vitro airway MRSA infection model. 18β-GA enhanced the bactericidal activity of the aminoglycosides tobramycin, gentamicin and amikacin, and of polymyxin B against two MRSA strains, reducing the MIC of these antibiotics 32–64-fold [fractional inhibitory concentration index (FICI) of 0.12–0.13]. Other β-amyrin triterpenoids and α-amyrin triterpenoids did not exert such synergistic effects. 18β-GA did not enhance the activity of antibiotics from other structural classes against the MRSA strains. In an air-exposed airway epithelial cell culture, 18β-GA enhanced the bactericidal activity of tobramycin and polymyxin B against the MRSA strain. These data demonstrate the potential of 18β-GA to synergise with certain types of antibiotics to eliminate strains of MRSA.

Centers for Disease Control and Prevention (CDC) (2014) Antibiotic resistance threats in the United States, 2013. U.S. Department of Health and Human Services, Atlanta, GA, USA

David MZ, Medvedev S, Hohmann SF, Ewigman B, Daum RS (2012) Increasing burden of methicillin-resistant Staphylococcus aureus hospitalizations at US academic medical centers, 2003–2008. Infect Control Hosp Epidemiol 33(8):782–789CrossRefPubMedPubMedCentral

Abreu AC, McBain AJ, Simões M (2012) Plants as sources of new antimicrobials and resistance-modifying agents. Nat Prod Rep 29(9):1007–1021CrossRefPubMed

Gill EE, Franco OL, Hancock RE (2015) Antibiotic adjuvants: diverse strategies for controlling drug-resistant pathogens. Chem Biol Drug Des 85(1):56–78CrossRefPubMedPubMedCentral

Gibbons S, Oluwatuyi M, Veitch NC, Gray AI (2003) Bacterial resistance modifying agents from Lycopus europaeus. Phytochemistry 62(1):83–87CrossRefPubMed

Marquez B, Neuville L, Moreau NJ, Genet JP, dos Santos AF, Caño de Andrade MC, Sant’Ana AE (2005) Multidrug resistance reversal agent from Jatropha elliptica. Phytochemistry 66(15):1804–1811CrossRefPubMed

Oluwatuyi M, Kaatz GW, Gibbons S (2004) Antibacterial and resistance modifying activity of Rosmarinus officinalis. Phytochemistry 65(24):3249–3254CrossRefPubMed

Podoll JD, Liu Y, Chang L, Walls S, Wang W, Wang X (2013) Bio-inspired synthesis yields a tricyclic indoline that selectively resensitizes methicillin-resistant Staphylococcus aureus (MRSA) to beta-lactam antibiotics. Proc Natl Acad Sci U S A 110(39):15573–15578CrossRefPubMedPubMedCentral

Shibata H, Kondo K, Katsuyama R, Kawazoe K, Sato Y, Murakami K, Takaishi Y, Arakaki N, Higuti T (2005) Alkyl gallates, intensifiers of beta-lactam susceptibility in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 49(2):549–555CrossRefPubMedPubMedCentral

10.

Stapleton PD, Shah S, Anderson JC, Hara Y, Hamilton-Miller JM, Taylor PW (2004) Modulation of beta-lactam resistance in Staphylococcus aureus by catechins and gallates. Int J Antimicrob Agents 23(5):462–467CrossRefPubMed

11.

Zhou X, Zhao L, Liu X, Li X, Jia F, Zhang Y, Wang Y (2012) Antimycobacterial and synergistic effects of 18beta-glycyrrhetinic acid or glycyrrhetinic acid-30-piperazine in combination with isoniazid, rifampicin or streptomycin against Mycobacterium bovis. Phytother Res 26(2):253–258CrossRefPubMed

12.

Beseda I, Czollner L, Shah PS, Khunt R, Gaware R, Kosma P, Stanetty C, Del Ruiz-Ruiz MC, Amer H, Mereiter K, Da Cunha T, Odermatt A, Classen-Houben D, Jordis U (2010) Synthesis of glycyrrhetinic acid derivatives for the treatment of metabolic diseases. Bioorg Med Chem 18(1):433–454CrossRefPubMed

13.

Croes S, Deurenberg RH, Boumans ML, Beisser PS, Neef C, Stobberingh EE (2009) Staphylococcus aureus biofilm formation at the physiologic glucose concentration depends on the S. aureus lineage. BMC Microbiol 9:229CrossRefPubMedPubMedCentral

14.

Meletiadis J, Pournaras S, Roilides E, Walsh TJ (2010) Defining fractional inhibitory concentration index cutoffs for additive interactions based on self-drug additive combinations, Monte Carlo simulation analysis, and in vitro-in vivo correlation data for antifungal drug combinations against Aspergillus fumigatus. Antimicrob Agents Chemother 54(2):602–609CrossRefPubMedPubMedCentral

15.

Odds FC (2003) Synergy, antagonism, and what the chequerboard puts between them. J Antimicrob Chemother 52(1):1CrossRefPubMed

16.

Lee JC, Koerten H, van den Broek P, Beekhuizen H, Wolterbeek R, van den Barselaar M, van der Reijden T, van der Meer J, van de Gevel J, Dijkshoorn L (2006) Adherence of Acinetobacter baumannii strains to human bronchial epithelial cells. Res Microbiol 157(4):360–366CrossRefPubMed

17.

Schrumpf JA, van Sterkenburg MA, Verhoosel RM, Zuyderduyn S, Hiemstra PS (2012) Interleukin 13 exposure enhances vitamin D-mediated expression of the human cathelicidin antimicrobial peptide 18/LL-37 in bronchial epithelial cells. Infect Immun 80(12):4485–4494CrossRefPubMedPubMedCentral

18.

Zuyderduyn S, Ninaber DK, Schrumpf JA, van Sterkenburg MA, Verhoosel RM, Prins FA, van Wetering S, Rabe KF, Hiemstra PS (2011) IL-4 and IL-13 exposure during mucociliary differentiation of bronchial epithelial cells increases antimicrobial activity and expression of antimicrobial peptides. Respir Res 12:59CrossRefPubMedPubMedCentral

19.

Vakulenko SB, Mobashery S (2003) Versatility of aminoglycosides and prospects for their future. Clin Microbiol Rev 16(3):430–450CrossRefPubMedPubMedCentral

20.

Welte T, Pletz MW (2010) Antimicrobial treatment of nosocomial meticillin-resistant Staphylococcus aureus (MRSA) pneumonia: current and future options. Int J Antimicrob Agents 36(5):391–400CrossRefPubMed

21.

Zavascki AP, Goldani LZ, Li J, Nation RL (2007) Polymyxin B for the treatment of multidrug-resistant pathogens: a critical review. J Antimicrob Chemother 60(6):1206–1215CrossRefPubMed

22.

Chintharlapalli S, Papineni S, Jutooru I, McAlees A, Safe S (2007) Structure-dependent activity of glycyrrhetinic acid derivatives as peroxisome proliferator-activated receptor {gamma} agonists in colon cancer cells. Mol Cancer Ther 6(5):1588–1598CrossRefPubMed

23.

Classen-Houben D, Schuster D, Da Cunha T, Odermatt A, Wolber G, Jordis U, Kueenburg B (2009) Selective inhibition of 11beta-hydroxysteroid dehydrogenase 1 by 18alpha-glycyrrhetinic acid but not 18beta-glycyrrhetinic acid. J Steroid Biochem Mol Biol 113(3–5):248–252CrossRefPubMed

24.

Matchkov VV, Rahman A, Peng H, Nilsson H, Aalkjaer C (2004) Junctional and nonjunctional effects of heptanol and glycyrrhetinic acid derivates in rat mesenteric small arteries. Br J Pharmacol 142(6):961–972CrossRefPubMedPubMedCentral

25.

Zani F, Cuzzoni MT, Daglia M, Benvenuti S, Vampa G, Mazza P (1993) Inhibition of mutagenicity in Salmonella typhimurium by Glycyrrhiza glabra extract, glycyrrhizinic acid, 18 alpha- and 18 beta-glycyrrhetinic acids. Planta Med 59(6):502–507CrossRefPubMed

26.

Chagnon F, Guay I, Bonin MA, Mitchell G, Bouarab K, Malouin F, Marsault É (2014) Unraveling the structure–activity relationship of tomatidine, a steroid alkaloid with unique antibiotic properties against persistent forms of Staphylococcus aureus. Eur J Med Chem 80:605–620CrossRefPubMed

27.

Mitchell G, Lafrance M, Boulanger S, Séguin DL, Guay I, Gattuso M, Marsault E, Bouarab K, Malouin F (2012) Tomatidine acts in synergy with aminoglycoside antibiotics against multiresistant Staphylococcus aureus and prevents virulence gene expression. J Antimicrob Chemother 67(3):559–568CrossRefPubMed

28.

de León L, Beltrán B, Moujir L (2005) Antimicrobial activity of 6-oxophenolic triterpenoids. Mode of action against Bacillus subtilis. Planta Med 71(4):313–319CrossRefPubMed

29.

Dwivedi GR, Maurya A, Yadav DK, Khan F, Darokar MP, Srivastava SK (2015) Drug resistance reversal potential of ursolic acid derivatives against nalidixic acid- and multidrug-resistant Escherichia coli. Chem Biol Drug Des 86(3):272–283CrossRefPubMed

30.

Chung PY, Chung LY, Navaratnam P (2014) Potential targets by pentacyclic triterpenoids from Callicarpa farinosa against methicillin-resistant and sensitive Staphylococcus aureus. Fitoterapia 94:48–54CrossRefPubMed

31.

Long DR, Mead J, Hendricks JM, Hardy ME, Voyich JM (2013) 18beta-Glycyrrhetinic acid inhibits methicillin-resistant Staphylococcus aureus survival and attenuates virulence gene expression. Antimicrob Agents Chemother 57(1):241–247CrossRefPubMedPubMedCentral

32.

Haisma EM, de Breij A, Chan H, van Dissel JT, Drijfhout JW, Hiemstra PS, El Ghalbzouri A, Nibbering PH (2014) LL-37-derived peptides eradicate multidrug-resistant Staphylococcus aureus from thermally wounded human skin equivalents. Antimicrob Agents Chemother 58(8):4411–4419CrossRefPubMedPubMedCentral

33.

Cosmetic Ingredient Review Expert Panel (2007) Final report on the safety assessment of Glycyrrhetinic Acid, Potassium Glycyrrhetinate, Disodium Succinoyl Glycyrrhetinate, Glyceryl Glycyrrhetinate, Glycyrrhetinyl Stearate, Stearyl Glycyrrhetinate, Glycyrrhizic Acid, Ammonium Glycyrrhizate, Dipotassium Glycyrrhizate, Disodium Glycyrrhizate, Trisodium Glycyrrhizate, Methyl Glycyrrhizate, and Potassium Glycyrrhizinate. Int J Toxicol 26(Suppl 2):79–112

34.

Li HE, Qiu JZ, Yang ZQ, Dong J, Wang JF, Luo MJ, Pan J, Dai XH, Zhang Y, Song BL, Deng XM (2012) Glycyrrhetinic acid protects mice from Staphylococcus aureus pneumonia. Fitoterapia 83(1):241–248CrossRefPubMed

35.

Allen HB, Vaze ND, Choi C, Hailu T, Tulbert BH, Cusack CA, Joshi SG (2014) The presence and impact of biofilm-producing staphylococci in atopic dermatitis. JAMA Dermatol 150(3):260–265CrossRefPubMed

36.

Wichmann K, Uter W, Weiss J, Breuer K, Heratizadeh A, Mai U, Werfel T (2009) Isolation of alpha-toxin-producing Staphylococcus aureus from the skin of highly sensitized adult patients with severe atopic dermatitis. Br J Dermatol 161(2):300–305CrossRefPubMed

Titel: The licorice pentacyclic triterpenoid component 18β-glycyrrhetinic acid enhances the activity of antibiotics against strains of methicillin-resistant Staphylococcus aureus
verfasst von: A. de Breij
T. G. Karnaoukh
J. Schrumpf
P. S. Hiemstra
P. H. Nibbering
J. T. van Dissel
P. C. de Visser
Publikationsdatum: 15.01.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Clinical Microbiology & Infectious Diseases / Ausgabe 4/2016
Print ISSN: 0934-9723
Elektronische ISSN: 1435-4373
DOI: https://doi.org/10.1007/s10096-015-2570-z

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Echinokokkose medikamentös behandeln oder operieren?

06.05.2024 DCK 2024 Kongressbericht

Die Therapie von Echinokokkosen sollte immer in spezialisierten Zentren erfolgen. Eine symptomlose Echinokokkose kann – egal ob von Hunde- oder Fuchsbandwurm ausgelöst – konservativ erfolgen. Wenn eine Op. nötig ist, kann es sinnvoll sein, vorher Zysten zu leeren und zu desinfizieren.

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Proximale Humerusfraktur: Auch 100-Jährige operieren?

01.05.2024 DCK 2024 Kongressbericht

Mit dem demographischen Wandel versorgt auch die Chirurgie immer mehr betagte Menschen. Von Entwicklungen wie Fast-Track können auch ältere Menschen profitieren und bei proximaler Humerusfraktur können selbst manche 100-Jährige noch sicher operiert werden.

Die „Zehn Gebote“ des Endokarditis-Managements

30.04.2024 Endokarditis Leitlinie kompakt

Worauf kommt es beim Management von Personen mit infektiöser Endokarditis an? Eine Kardiologin und ein Kardiologe fassen die zehn wichtigsten Punkte der neuen ESC-Leitlinie zusammen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2016

High positive predictive value of Gram stain on catheter-drawn blood samples for the diagnosis of catheter-related bloodstream infection in intensive care neonates

Management of septic shock and severe infections in migrants and returning travelers requiring critical care

Cytotoxic immune responses in the lungs correlate to disease severity in patients with hantavirus infection

Real-world effectiveness of peginterferon α-2b plus ribavirin in a Canadian cohort of treatment-naïve chronic hepatitis C patients with genotypes 2 or 3: results of the PoWer and RediPEN studies

In vivo development of daptomycin resistance in vancomycin-susceptible methicillin-resistant Staphylococcus aureus severe infections previously treated with glycopeptides