Skip to main content

Advertisement

SpringerLink
Log in

In vitro and in silico evaluation of some plant extracts and phytocompounds against multidrug-resistant Gram-negative bacteria

  • Research Article
  • Published:
Advances in Traditional Medicine Aims and scope Submit manuscript

Abstract

The spread of multidrug-resistant Gram-negative (MDR) bacteria is a global public health problem, as infections caused by MDR Gram-negative bacteria are difficult to treat. New antibiotic agents need to be developed to overcome this problem, and phytochemicals show promise at this point. In this study, methanol extracts were prepared from cinnamon, thyme, nettle, white tea, rosehip, and antibacterial activity of the methanol extracts was studied against two MDR Gram-Negative bacteria (K. pneumoniae and A. baumannii) by broth microdilution method. The MICs of methanol extracts of cinnamon, rosehip, thyme, white tea for A. baumannii were found as 0.015125 g/ml, 0.07825 g/ml, 0.030625 g/ml, 0.00796875 g/ml, respectively. It was found that only cinnamon methanol extract had antibacterial activity in the used extract concentrations against K. pneumoniae and the MIC value was 0.0605 g/ml. The effects of plant methanol extract with antibacterial activity and imipenem combinations were studied in vitro using the checkerboard method. The FIC Indexes were obtained from the checkerboard results and it was observed that the combination of methanol extract and imipenem showed an antagonistic or additive/indifferent effect but not a synergistic effect. We evaluated the binding affinity of epigallocatechin 3-gallate, quercetin, cinnamaldehyde, carvacrol, and thymol phytocompounds using in silico methods, which are well known as a phytocompounds in white tea, cinnamon, thyme, nettle, and rosehip and have antibacterial activities. The results suggested that these phytocompounds should be supported with in vivo and in vitro experiments to investigate their potential for being inhibitor candidates.

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
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Aboulmagd E, Al-Mohammed H, Al-Badry S (2011) Synergism and postantibiotic effect of green tea extract and imipenem against methicillin-resistant Staphylococcus aureus. Microbiol J 1:89–96

    Article  Google Scholar 

  • Averill F, Painter G (1992) Steepest-descent determination of occupation numbers and energy minimization in the local-density approximation. Phys Rev B 46:2498

    Article  CAS  Google Scholar 

  • Bal Ç (1999) Antibiyotik Kombinasyonlarının In vitro Etkinliğinin Saptanması Flora İnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Dergisi 4:219–229

  • Bassetti M, Peghin M, Vena A, Giacobbe DR (2019) Treatment of infections due to MDR Gram-negative bacteria. Front Med 6:74

    Article  Google Scholar 

  • Berman H et al (2000) The protein data Bank nucleic acids research 28:235–242. https://www.rcsb.org

  • Bonapace CR, White RL, Friedrich LV, Bosso JA (2000) Evaluation of antibiotic synergy against Acinetobacter baumannii: a comparison with Etest, time-kill, and checkerboard methods. Diagn Microbiol Infect Disease 38:43–50

    Article  CAS  Google Scholar 

  • Case D et al (2014) (2014) AMBER 14. University of California, San Francisco

    Google Scholar 

  • Chuah E, Zakaria Z, Suhaili Z, Bakar SA, Desa M (2014) Antimicrobial activities of plant extracts against methicillin-susceptible and methicillin-resistant Staphylococcus aureus. J Microbiol Res 4:6–13

    Google Scholar 

  • Cicek AC, Saral A, Iraz M, Ceylan A, Duzgun A, Peleg A, Sandalli C (2014) OXA-and GES-type β-lactamases predominate in extensively drug-resistant Acinetobacter baumannii isolates from a Turkish University Hospital. Clin Microbiol Infect 20:410–415

    Article  PubMed  CAS  Google Scholar 

  • Dhama K et al (2014) Evidence based antibacterial potentials of medicinal plants and herbs countering bacterial pathogens especially in the era of emerging drug resistance: an integrated update. Int J Pharmacol 10:1–43

    Article  CAS  Google Scholar 

  • Dhara L, Tripathi A (2020) Cinnamaldehyde: a compound with antimicrobial and synergistic activity against ESBL-producing quinolone-resistant pathogenic Enterobacteriaceae. Eur J Clin Microbiol Infect Diseases 39:65–73

    Article  Google Scholar 

  • Doi Y (2019) Treatment options for carbapenem-resistant gram-negative bacterial infections. Clin Infect Dis 69:565–575

  • El-Hosseiny L, El-Shenawy M, Haroun M, Abdullah F (2014) Comparative evaluation of the inhibitory effect of some essential oils with antibiotics against Pseudomonas aeruginosa. Int J Antibiot

  • Eliopoulos GM, Maragakis LL, Perl TM (2008) Acinetobacter baumannii: epidemiology, antimicrobial resistance, and treatment options. Clin Infect Diseases 46:1254–1263

    Article  Google Scholar 

  • Evans BA, Amyes SG (2014) OXA β-Lactamases. Clin Microbiol Rev 27:241–263

    Article  PubMed  PubMed Central  Google Scholar 

  • Ev (2021) The European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters

  • Fadli M, Saad A, Sayadi S, Chevalier J, Mezrioui N-E, Pagès J-M, Hassani L (2012) Antibacterial activity of Thymus maroccanus and Thymus broussonetii essential oils against nosocomial infection–bacteria and their synergistic potential with antibiotics. Phytomedicine 19:464–471

    Article  PubMed  CAS  Google Scholar 

  • Fankam AG, Kuiate J-R, Kuete V (2017) Antibacterial and antibiotic resistance modulatory activities of leaves and bark extracts of Recinodindron heudelotii (Euphorbiaceae) against multidrug-resistant Gram-negative bacteria. BMC Complement Altern Med 17:1–6

    Article  Google Scholar 

  • Fankam AG, Kuiate JR, Kuete V (2015) Antibacterial and antibiotic resistance modifying activity of the extracts from Allanblackia gabonensis, Combretum molle and Gladiolus quartinianus against Gram-negative bacteria including multi-drug resistant phenotypes. BMC Complement Altern Med 15:1–12

    Article  Google Scholar 

  • Forli W, Halliday S, Belew R, Olson AJ (2012) AutoDock Version 4.2. J Med Chem 55:623–638

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ginovyan M, Trchounian A (2019) Novel approach to combat antibiotic resistance: evaluation of some Armenian herb crude extracts for their antibiotic modulatory and antiviral properties. J Appl Microbiol 127:472–480

    Article  PubMed  CAS  Google Scholar 

  • Hacioglu M, Dosler S, Tan ASB, Otuk G (2017) Antimicrobial activities of widely consumed herbal teas, alone or in combination with antibiotics: an in vitro study. PeerJ 5:e3467

    Article  PubMed  PubMed Central  Google Scholar 

  • Howard A, O’Donoghue M, Feeney A, Sleator RD (2012) Acinetobacter baumannii: an emerging opportunistic pathogen. Virulence 3:243–250

    Article  PubMed  PubMed Central  Google Scholar 

  • Hu Z-Q, Zhao W-H, Asano N, Yoda Y, Hara Y, Shimamura T (2002) Epigallocatechin gallate synergistically enhances the activity of carbapenems against methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 46:558–560

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kaskatepe B, Kiymaci ME, Suzuk S, Erdem SA, Cesur S, Yildiz S (2016) Antibacterial effects of cinnamon oil against carbapenem resistant nosocomial Acinetobacter baumannii and Pseudomonas aeruginosa isolates. Ind Crops Prod 81:191–194

    Article  CAS  Google Scholar 

  • Keynan Y, Rubinstein E (2007) The changing face of Klebsiella pneumoniae infections in the community. Int J Antimicrob Agents 30:385–389

    Article  PubMed  CAS  Google Scholar 

  • Khan I et al (2020) Antimicrobial potential of the food-grade additive carvacrol against uropathogenic E. coli based on membrane depolarization, reactive oxygen species generation, and molecular docking analysis. Microbial Pathog 142:104046

    Article  CAS  Google Scholar 

  • Khazaei M, Khazaei M, Pazhouhi M (2020) An overview of therapeutic potentials of Rosa canina: a traditionally valuable herb. WCRJ 7:e1580

    Google Scholar 

  • Koulenti D, Song A, Ellingboe A, Abdul-Aziz MH, Harris P, Gavey E, Lipman J (2019) Infections by multidrug-resistant Gram-negative Bacteria: What’s new in our arsenal and what’s in the pipeline? Int J Antimicrob Agents 53:211–224

    Article  PubMed  CAS  Google Scholar 

  • Liu DC, Nocedal J (1989) On the limited memory BFGS method for large scale optimization. Math Program 45:503–528

    Article  Google Scholar 

  • Magiorakos A-P et al (2012) Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 18:268–281

    Article  PubMed  CAS  Google Scholar 

  • Maier JA, Martinez C, Kasavajhala K, Wickstrom L, Hauser KE, Simmerling C (2015) ff14SB: improving the accuracy of protein side chain and backbone parameters from ff99SB. J Chem Theory Comput 11:3696–3713

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Martyna GJ, Klein ML, Tuckerman M (1992) Nosé-Hoover chains: The canonical ensemble via continuous dynamics. J Chem Phys 97:2635–2643

    Article  Google Scholar 

  • Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, Olson AJ (1998) Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem 19:1639–1662

    Article  CAS  Google Scholar 

  • Mugnier PD, Poirel L, Naas T, Nordmann P (2010) Worldwide dissemination of the blaOXA-23 Carbapenemase gene of Acinetobacter baumannii1. Emerg Infect Diseases 16:35

    Article  CAS  Google Scholar 

  • Nocedo-Mena D, Garza-González E, González-Ferrara M, del Rayo C-C (2020) Antibacterial activity of Cissus incisa extracts against multidrug-resistant bacteria. Curr Top Med Chem 20:318–323

    Article  PubMed  CAS  Google Scholar 

  • Osterburg A, Gardner J, Hyon S, Neely A, Babcock G (2009) Highly antibiotic-resistant Acinetobacter baumannii clinical isolates are killed by the green tea polyphenol (–)-epigallocatechin-3-gallate (EGCG). Clin Microbiol Infect 15:341–346

    Article  PubMed  CAS  Google Scholar 

  • Paczosa MK, Mecsas J (2016) Klebsiella pneumoniae: going on the offense with a strong defense. Microbiol Mol Biol Rev 80:629–661

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Radji M, Agustama RA, Elya B, Tjampakasari CR (2013) Antimicrobial activity of green tea extract against isolates of methicillin–resistant Staphylococcus aureus and multi–drug resistant Pseudomonas aeruginosa. Asian Pacific J Trop Biomed 3:663–667

    Article  CAS  Google Scholar 

  • Raei P et al (2017) Thymol and carvacrol strongly inhibit biofilm formation and growth of carbapenemase-producing Gram negative bacilli. Cell Mol Biol (noisy-Le-Grand) 63:108–112

    Article  CAS  Google Scholar 

  • Salehzadeh A, Asadpour L, Naeemi AS, Houshmand E (2014) Antimicrobial activity of methanolic extracts of Sambucus ebulus and Urtica dioica against clinical isolates of methicillin resistant Staphylococcus aureus African Journal of Traditional. Complement Altern Med 11:38–40

    Google Scholar 

  • Santiago C (2015) Application of plant metabolites to overcome antibiotic resistance of methicillin resistant Staphylococcus aureus (MRSA). University of Nottingham

  • Schrödinger L (2015) The PyMOL molecular graphics system, version 1.8. November

  • Silva DM, Costa PA, Ribon AO, Purgato GA, Gaspar D-M, Diaz MA (2019) Plant extracts display synergism with different classes of antibiotics. Anais da Acad Brasil de Ciênc 91

  • Smith CA et al (2013) Structural basis for carbapenemase activity of the OXA-23 β-lactamase from Acinetobacter baumannii. Chem Biol 20:1107–1115

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Torol S, Kasap M (2013) Purification and characterization of OXA-23 from Acinetobacter baumannii. J Enzyme Inhibit Med Chem 28:836–842

    Article  CAS  Google Scholar 

  • Usman Amin M et al (2016) Effects of luteolin and quercetin in combination with some conventional antibiotics against methicillin-resistant Staphylococcus aureus. Int J Mol Sci 17:1947

    Article  PubMed Central  Google Scholar 

  • Wang J, Wolf RM, Caldwell JW, Kollman PA, Case DA (2004) Development and testing of a general amber force field. J Comput Chem 25:1157–1174

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank the Trabzon Fatih State Hospital and Dr. Tuba Kose for providing Acinetobacter baumannii and Klebsiella pneumoniae isolates. Numerical calculations including MD simulations were carried out at TUBITAK ULAKBIM (TURKEY), High Performance, and Grid Computing Center (TRUBA). This study was supported by grants from Artvin Coruh University (BAP- 2018.F83.02.03).

Author information

Authors and Affiliations

  1. Biology, Graduate Education Institute, Artvin Coruh University, 08000, Artvin, Turkey

    Eda Aydemir

  2. Vocational School of Health Services, Medical Laboratory Techniques, Artvin Coruh University, 08000, Artvin, Turkey

    Emrah Sarıyer

  3. Department of Nursing, Faculty of Health Sciences, Gumushane University, 29100, Gumushane, Turkey

    Esma Akyıldız

  4. Department of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, Gumushane University, 29100, Gumushane, Turkey

    Azer Özad Düzgün

  5. Vocational School of Health Services, Pharmacy Services Program, Artvin Coruh University, 08000, Artvin, Turkey

    Yasemin Camadan

  6. Department of Nutrition and Dietetics, Faculty of Health Sciences, 08000, Artvin, Turkey

    Ayşegül Saral Sarıyer

Authors
  1. Eda Aydemir
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Emrah Sarıyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Esma Akyıldız
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Azer Özad Düzgün
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yasemin Camadan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ayşegül Saral Sarıyer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ayşegül Saral Sarıyer.

Ethics declarations

Ethical statement

This article does not contain any studies involving animals performed by any of the authors. This article does not contain any studies involving human participants performed by any of the authors.

Conflict of interest

Eda Aydemir has no conflict of interest. Emrah Sarıyer has no conflict of interest. Esma Akyıldız has no conflict of interest. Azer Özad Düzgün has no conflict of interest. Yasemin Camadan has no conflict of interest. Ayşegül Saral Sarıyer has 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

Aydemir, E., Sarıyer, E., Akyıldız, E. et al. In vitro and in silico evaluation of some plant extracts and phytocompounds against multidrug-resistant Gram-negative bacteria. ADV TRADIT MED (ADTM) 22, 749–759 (2022). https://doi.org/10.1007/s13596-021-00602-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13596-021-00602-6

Keywords

Search

Navigation