Planta Med 2012; 78(17): 1824-1830
DOI: 10.1055/s-0032-1315388
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Vitamin C Inhibits Staphylococcus aureus Growth and Enhances the Inhibitory Effect of Quercetin on Growth of Escherichia coli In Vitro

Johanna Kallio
1   CEMIS-Oulu, Kajaani University Consortium, University of Oulu, Sotkamo, Finland
Mari Jaakkola
1   CEMIS-Oulu, Kajaani University Consortium, University of Oulu, Sotkamo, Finland
Marianne Mäki
1   CEMIS-Oulu, Kajaani University Consortium, University of Oulu, Sotkamo, Finland
Pekka Kilpeläinen
Vesa Virtanen
1   CEMIS-Oulu, Kajaani University Consortium, University of Oulu, Sotkamo, Finland
› Author Affiliations
Further Information

Publication History

received 14 May 2012
revised 31 July 2012

accepted 31 August 2012

Publication Date:
11 October 2012 (online)


Quercetin is a natural flavonoid possessing a number of health beneficial effects. Its bioactivity is restricted by low solubility and sensitivity to oxidative degradation, factors that are often ignored in laboratory studies. We studied the antimicrobial effects of quercetin on Staphylococcus aureus, Escherichia coli and Lactobacillus plantarum at concentrations at which it is soluble and investigated how the antioxidant vitamin C modulates these activities. S. aureus was the most sensitive of the studied bacteria. After 12 hours of culturing, 90 µM quercetin decreased the growth of S. aureus to 75 % of the value for a control culture. 1 mM vitamin C combined with 90 µM quercetin diminished the growth of S. aureus drastically to 3 % of that of the control culture supplemented with vitamin C only. Interestingly, vitamin C by itself inhibited the growth of S. aureus as well, and 5 mM vitamin C inhibited growth completely. The growth inhibition of E. coli was slightly but significantly better in the presence of both quercetin and vitamin C than in the presence of quercetin alone. Probiotic L. plantarum was resistant to quercetin in the presence and absence of vitamin C. Enhancement of quercetinʼs antimicrobial activity by vitamin C is partly explained by the stabilizing effect of vitamin C on quercetin. Even though the acidity of vitamin C contributes to the inhibition of S. aureus growth, neutralized vitamin C also inhibits the growth efficiently even without quercetin. Our results suggest that vitamin C affects the metabolism of S. aureus and that these changes are likely to result in the observed growth inhibition. Although vitamin C itself is a powerful antioxidant, its aerobic metabolism increases oxidative stress on bacterial cells. Vitamin C may therefore be a safe and natural alternative for restricting the growth of S. aureus when non-toxicity is required.

Supporting Information

  • References

  • 1 Kelly GS. Quercetin. Monograph Altern Med Rev 2011; 16: 172-194
  • 2 Edwards RL, Lyon T, Litwin SE, Rabovsky A, Symons JD, Jalili T. Quercetin reduces blood pressure in hypertensive subjects. J Nutr 2007; 137: 2405-2411
  • 3 Basile A, Sorbo S, Giordano S, Ricciardi L, Ferrara S, Montesano D, Castaldo Cobianchi R, Vuotto ML, Ferrara L. Antibacterial and allelopathic activity of extract from Castanea sativa leaves. Fitoterapia 2000; 71 (Suppl. 01) S110-S116
  • 4 Gatto MT, Falcocchio S, Grippa E, Mazzanti G, Battinelli L, Nicolosi G, Lambusta D, Saso L. Antimicrobial and anti-lipase activity of quercetin and its C2–C16 3-O-acyl-esters. Bioorg Med Chem 2002; 10: 269-272
  • 5 Cushnie TP, Lamb AJ. Antimicrobial activity of flavonoids. Int J Antimicrob Agents 2005; 26: 343-356
  • 6 González-Segovia R, Quintanar JL, Salinas E, Ceballos-Salazar R, Aviles-Jiménez F, Torres-López J. Effect of the flavonoid quercetin on inflammation and lipid peroxidation induced by Helicobacter pylori in gastric mucosa of guinea pig. J Gastroenterol 2008; 43: 441-447
  • 7 Hatano T, Tsugawa M, Kusuda M, Taniguchi S, Yoshida T, Shiota S, Tsuchiya T. Enhancement of antibacterial effects of epigallocatechin gallate, using ascorbic acid. Phytochemistry 2008; 69: 3111-3116
  • 8 Lin RD, Chin YP, Hou WC, Lee MH. The effects of antibiotics combined with natural polyphenols against clinical methicillin-resistant Staphylococcus aureus (MRSA). Planta Med 2008; 74: 840-846
  • 9 Parkar SG, Stevenson DE, Skinner MA. The potential influence of fruit polyphenols on colonic microflora and human gut health. Int J Food Microbiol 2008; 124: 295-298
  • 10 García-Ruiz A, Moreno-Arribas MV, Martín-Álvarez PJ, Bartolomé B. Comparative study of the inhibitory effects of wine polyphenols on the growth of enological lactic acid bacteria. Int J Food Microbiol 2011; 145: 426-431
  • 11 Srinivas K, King JW, Howard LR, Monrad JK. Solubility and solution thermodynamic properties of quercetin and quercetin dihydrate in subcritical water. J Food Eng 2010; 100: 208-218
  • 12 Gao L, Liu G, Wang X, Liu F, Xu Y, Ma J. Preparation of a chemically stable quercetin formulation using nanosuspension technology. Int J Pharm 2011; 404: 231-237
  • 13 Kim MK, Park KS, Lee C, Park HR, Choo H, Chong Y. Enhanced stability and intracellular accumulation of quercetin by protection of the chemically or metabolically susceptible hydroxyl groups with a pivaloxymethyl (POM) promoiety. J Med Chem 2010; 53: 8597-8607
  • 14 van der Woude H, Gliszczyńska-Šwiglo A, Struijs K, Smeets A, Alink GM, Rietjens IM. Biphasic modulation of cell proliferation by quercetin at concentrations physiologically relevant in humans. Cancer Lett 2003; 200: 41-47
  • 15 Vrijsen R, Everaert L, Boeyé A. Antiviral activity of flavones and potentiation by ascorbate. J Gen Virol 1988; 69 (Pt. 7) 1749-1751
  • 16 Halliwell B. Oxidative stress in cell culture: an under-appreciated problem?. FEBS Lett 2003; 540: 3-6
  • 17 McCarrell EM, Gould SW, Fielder MD, Kelly AF, El Sankary W, Naughton DP. Antimicrobial activities of pomegranate rind extracts: enhancement by addition of metal salts and vitamin C. BMC Complement Altern Med 2008; 8: 64
  • 18 Häkkinen SH, Kärenlampi SO, Mykkänen HM, Törrönen AR. Influence of domestic processing and storage on flavonol contents in berries. J Agric Food Chem 2000; 48: 2960-2965
  • 19 Chung DM, Chung YC, Maeng PJ, Chun HK. Regioselective deglycosylation of onion quercetin glucosides by Saccharomyces cerevisiae . Biotechnol Lett 2011; 33: 783-786
  • 20 Rauha JP, Remes S, Heinonen M, Hopia A, Kähkönen M, Kujala T, Pihlaja K, Vuorela H, Vuorela P. Antimicrobial effects of Finnish plant extracts containing flavonoids and other phenolic compounds. Int J Food Microbiol 2000; 56: 3-12
  • 21 Alvarez MA, Debattista NB, Pappano NB. Antimicrobial activity and synergism of some substituted flavonoids. Folia Microbiol (Praha) 2008; 53: 23-28
  • 22 Akroum S, Bendjeddou D, Satta D, Lalaoui K. Antibacterial, antioxidant and acute toxicity tests on flavonoids extracted from some medicinal plants. Int J Green Pharm 2010; 4: 165-169
  • 23 Rattanachaikunsopon P, Phumkhachorn P. Contents and antibacterial activity of flavonoids extracted from leaves of Psidium guajava . J Med Plant Res 2010; 4: 393-396
  • 24 Panula-Perälä J, Šiurkus J, Vasala A, Wilmanowski R, Casteleijn MG, Neubauer P. Enzyme controlled glucose auto-delivery for high cell density cultivations in microplates and shake flasks. Microb Cell Fact 2008; 7: 31
  • 25 Cueva C, Moreno-Arribas MV, Martin-Alvarez PJ, Bills G, Vicente MF, Basilio A, Rivas CL, Requena T, Rodriguez JM, Bartolome B. Antimicrobial activity of phenolic acids against commensal, probiotic and pathogenic bacteria. Res Microbiol 2010; 161: 372-382
  • 26 Puupponen-Pimiä R, Nohynek L, Hartmann-Schmidlin S, Kähkönen M, Heinonen M, Määttä-Riihinen K, Oksman-Caldentey KM. Berry phenolics selectively inhibit the growth of intestinal pathogens. J Appl Microbiol 2005; 98: 991-1000
  • 27 Tassou C, Koutsoumanis K, Nychas G-JE. Inhibition of Salmonella enteritidis and Staphylococcus aureus in nutrient broth by mint essential oil. Food Res Int 2000; 33: 273-280
  • 28 Kylli P, Nohynek L, Puupponen-Pimiä R, Westerlund-Wikström B, McDougall G, Stewart D, Heinonen M. Rowanberry phenolics: compositional analysis and bioactivities. J Agric Food Chem 2010; 58: 11985-11992
  • 29 Rodríguez H, Curiel J, Landete JM, de las Rivas B, López de Felipe F, Gómez-Cordovés C, Mancheño JM, Muñoz R. Food phenolics and lactic acid bacteria. Int J Food Microbiol 2009; 132: 79-90
  • 30 Ou T-I. Bactericide composition. US Patent Application Publication 2009/0253785 A1; 2009
  • 31 Amabile-Cuevas CF, Pina-Zentella R, Wah-Laborde ME. Decreased resistance to antibiotics and plasmid loss in plasmid-carrying strains of Staphylococcus aureus treated with ascorbic acid. Mutat Res 1991; 264: 119-125
  • 32 Rawal BD. Ascorbic acid: preferential lysis and catalase induction in antibiotic-resistant strains of Staphylococcus aureus . J Pharm Sci 1973; 62: 837-838
  • 33 Carpenter CE, Broadbent JR. External concentration of organic acid anions and pH: key independent variables for studying how organic acids inhibit growth of bacteria in mildly acidic foods. J Food Sci 2009; 74: R12-R15
  • 34 Zhang Z, Aboulwafa M, Smith MH, Saier Jr. MH. The ascorbate transporter of Escherichia coli . J Bacteriol 2003; 185: 2243-2250
  • 35 Campos E, Montella C, Garces F, Baldoma L, Aguilar J, Badia J. Aerobic L-ascorbate metabolism and associated oxidative stress in Escherichia coli . Microbiology 2007; 153: 3399-3408
  • 36 Linares D, Michaud P, Delort AM, Traikia M, Warrand J. Catabolism of L-ascorbate by Lactobacillus rhamnosus GG. J Agric Food Chem 2011; 59: 4140-4147