• Savita Jandaik Shoolini University
  • Jyoti Mehta Shoolini University
  • Manindra Mohan Uttarakhand Council for Biotechnology (UCB)


Objective: The purpose of this study was to evaluate the synergistic and efflux pump inhibitory activities of some important medicinal plants collected
from Western Himalaya against different strains of Staphylococcus aureus to facilitate the reintroduction of therapeutically ineffective antibiotics back
into clinical use.
Methods: Various plant materials were extracted using methanol, ethyl acetate, and water. The dried extracts were screened for synergistic activity
by well diffusion method, and efflux pump inhibitory activity for plants extracts exhibiting maximum synergism assessed by berberine uptake assay
and ethidium bromide efflux inhibition assay, respectively.
Results: Methanolic extract (ME) and ethyl acetate extracts (EE) of most of the plant extracts showed synergistic activity with ciprofloxacin and
norfloxacin, whereas an aqueous extract showed no any synergistic activity. Maximum efflux pump inhibitory activity was observed for ME of Angelica
glauca followed by EE of Ficus carica.
Conclusion: ME of A. glauca exhibited potentials of efflux pump inhibition, and thus can, be used as an adjuvant with antibiotics to overcome the
problem of drug resistance due to efflux.
Keywords: Staphylococcus aureus, Therapeutically ineffective antibiotics, Synergistic effect, Efflux pump inhibitors.


Author Biographies


Research scholar

department of Microbiology


Savita Jandaik, Shoolini University

Associate Professor

Department of Microbiology

Jyoti Mehta, Shoolini University

Research scholar

Department of Microbiology

Manindra Mohan, Uttarakhand Council for Biotechnology (UCB)
Scientific Officer
Department of Biotechnology


1. Collier LH, Balows A, Sussman M. Topley and Wilson’s Microbiology
and Microbial Infections, Systematic Bacteriology. 2
ed. New York,
NY: Oxford University Press; 1999.
2. Metri BC, Peerapur BV, Jyothi P. Drug resistance patterns of clinical
isolates of Staphylococcus aureus in tertiary care center of South India.
Int J Pharm Pharm Sci 2015;7:70-2.
3. Schito GC. The importance of the development of antibiotic resistance
in Staphylococcus aureus. Clin Microbiol Infect 2006;12 Suppl 1:3-8.
4. Goldstein F. The potential clinical impact of low-level antibiotic
resistance in Staphylococcus aureus. J Antimicrob Chemother
5. Piddock LJ. Clinically relevant chromosomally encoded
multidrug resistance efflux pumps in bacteria. Clin Microbiol Rev
6. Stavri M, Piddock LJ, Gibbons S. Bacterial efflux pump inhibitors from
natural sources. J Antimicrob Chemother 2007;59(6):1247-60.
7. Neyfakh AA, Bidnenko VE, Chen LB. Efflux-mediated multidrug
resistance in Bacillus subtilis: Similarities and dissimilarities with the
mammalian system. Proc Natl Acad Sci U S A 1991;88(11):4781-5.
8. Markham PN, Westhaus E, Klyachko K, Johnson ME, Neyfakh AA.
Multiple novel inhibitors of the NorA multidrug transporter
of Staphylococcus aureus. Antimicrob Agents Chemother
9. Lomovskaya O, Warren MS, Lee A, Galazzo J, Fronko R, Lee M, et al.
Identification and characterization of inhibitors of multidrug resistance
efflux pumps in Pseudomonas aeruginosa: Novel agents for combination
therapy. Antimicrob Agents Chemother 2001;45(1):105-16.
10. Kannusamy G, Rengaswamy G. In vitro antibacterial activities of
Opuntia Ficus-indica stem and fruit extracts using disc diffusion
method. Int Curr Pharm J 2016;8(2):68-9.
11. Koduru SV, Grierson DS, Afolayan AJ. Ethnobotanical information
of medicinal plants used for treatment of cancer in the Eastern Cape
province, South Africa. Curr Sci 2007;92:906-8.
12. Handzlik J, Matys A, Kiec-Kononowicz K. Recent advances in multi-
drug resistance (MDR) efflux pump inhibitors of gram-positive bacteria
S. aureus. Antibiotics (Basel) 2013;2(1):28-45.
13. Sultana B, Anwar F, Ashraf M. Effect of extraction solvent/technique on
the antioxidant activity of selected medicinal plant extracts. Molecules
14. Mandal S, Mandal MD, Pal NK, Saha K. Synergistic anti-Staphylococcus
aureus activity of amoxicillin in combination with Emblica officinalis
and Nymphae odorata extracts. Asian Pac J Trop Dis 2010;60:711-4.
15. Belofsky G, Carreno R, Lewis K, Ball A, Casadei G, Tegos GP.
Metabolites of the smoke tree”, Dalea spinosa, potentiate antibiotic
activity against multidrug-resistant Staphylococcus aureus. J Nat Prod
16. Zechini B, Versace I. Inhibitors of multidrug resistant efflux systems in
bacteria. Recent Pat Antiinfect Drug Discov 2009;4(1):37-50.
17. Ibezim EC, Esimone CO, Nnamani PO, Onyishi IV, Brown SA,
Obodo SE. In vitro study of the interaction between some
fluoroquinolones and extracts of Kola nitida seed. Afr J Biotechnol
18. Yang ZC, Wang BC, Yang XS, Wang Q, Ran L. The synergistic activity
of antibiotics combined with eight traditional Chinese medicines
against two different strains of Staphylococcus aureus. Colloids Surf B
Biointerfaces 2005;41(2-3):79-81.
19. Aqil F, Khan MS, Owais M, Ahmad I. Effect of certain bioactive plant
extracts on clinical isolates of beta-lactamase producing methicillin
resistant Staphylococcus aureus. J Basic Microbiol 2005;45(2):106-14.
20. Adwan GM, Shanab BA, Adwan KM. In vitro activity of certain drugs
in combination with plant extracts against Staphylococcus aureus
infections. Pak J Med Sci 2008;24(4):541-4.
21. Betoni JE, Mantovani RP, Barbosa LN, Di Stasi LC,
Fernandes A Jr. Synergism between plant extract and antimicrobial
drugs used on Staphylococcus aureus diseases. Mem Inst Oswaldo
Cruz 2006;101(4):387-90.
22. Esimone CO, Iroha IR, Ibezim EC, Okeh CO, Okpana EM. In vitro
evaluation of the interaction between tea extracts and penicillin G
against Staphylococcus aureus. Afr J Biotechnol 2006;5:1082-6.
23. Darwish RM, Aburjai T, Al-Khalil S, Mahafzah A. Screening of
antibiotic resistant inhibitors from local plant materials against
two different strains of Staphylococcus aureus. J Ethnopharmacol
24. Braga LC, Leite AA, Xavier KG, Takahashi JA, Bemquerer MP,
Chartone-Souza E, et al. Synergic interaction between pomegranate
extract and antibiotics against Staphylococcus aureus. Can J Microbiol
25. Yam TS, Hamilton-Miller JM, Shah S. The effect of a component of
tea (Camellia sinensis) on methicillin resistance, PBP2’ synthesis, and
beta-lactamase production in Staphylococcus aureus. J Antimicrob
Chemother 1998;42(2):211-6.
26. Sibanda T, Okok AI. The challenges of overcoming antibiotic
resistance: Plant extracts as potential sources of antimicrobial and
resistance modifying agents. Afr J Biotechnol 2007;6(25):2886-96.
27. Gibbons S, Oluwatuyi M, Veitch NC, Gray AI. Bacterial resistance
modifying agents from Lycopus europaeus. Phytochemistry
28. Dickson RA, Houghton PJ, Hylands PJ, Gibbons S. Antimicrobial,
resistance-modifying effects, antioxidant and free radical scavenging
activities of Mezoneuron benthamianum Baill. Securinega virosa Roxb.
&Wlld. and Microglossa pyrifolia Lam. Phytother Res 2006;20(1):41-5.
29. Chang PC, Li HY, Tang HJ, Liu JW, Wang JJ, Chuang YC. In vitro
synergy of baicalein and gentamicin against vancomycin-resistant
Enterococcus. J Microbiol Immunol Infect 2007;40(1):56-61.
30. Horiuchi K, Shiota S, Kuroda T, Hatano T, Yoshida T, Tsuchiya T.
Asian J Pharm Clin Res, Vol 9, Suppl. 2, 2016, 277-282
Urmila et al.
Potentiation of antimicrobial activity of aminoglycosides by carnosol
from Salvia officinalis. Biol Pharm Bull 2007;30(2):287-90.
31. Ahmad I, Aqil F. In vitro efficacy of bioactive extracts of 15 medicinal
plants against ESbetaL-producing multidrug-resistant enteric bacteria.
Microbiol Res 2007;162(3):264-75.
32. Nascimento GG, Locatelli J, Freitas PC, Silva GL. Antibacterial
activity of plant extracts and phytochemicals on antibiotic-resistant
bacteria. Braz J Microbial 2000;31:247-56.
33. Hussaini RA, Adel MM. Antimicrobial and antiquorum sensing
activity of different parts of Lourus nobilis L. extracts. J Med
34. Rana T, Singh S, Kaur N, Pathania K, Farooq U. A review on efflux
pump inhibitors of medically important bacteria from plant sources. Int
J Pharm Sci Rev Res 2014;26(2):101-11.
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How to Cite
Urmila, S. Jandaik, J. Mehta, and M. Mohan. “SYNERGISTIC AND EFFLUX PUMP INHIBITORY ACTIVITY OF PLANT EXTRACTS AND ANTIBIOTICS ON STAPHYLOCOCCUS AUREUS STRAINS”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 9, no. 8, Oct. 2016, pp. 277-82, doi:10.22159/ajpcr.2016.v9s2.13801.
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