Abstract
Berry fruits are rich sources of bioactive compounds, such as phenolics and organic acids, which have antimicrobial activities against human pathogens. Among different berries and berry phenolics, cranberry, cloudberry, raspberry, strawberry and bilberry especially possess clear antimicrobial effects against, e.g. Salmonella and Staphylococcus. Complex phenolic polymers, like ellagitannins, are strong antibacterial agents present in cloudberry and raspberry. Several mechanisms of action in the growth inhibition of bacteria are involved, such as destabilisation of cytoplasmic membrane, permeabilisation of plasma membrane, inhibition of extracellular microbial enzymes, direct actions on microbial metabolism and deprivation of the substrates required for microbial growth. Antimicrobial activity of berries may also be related to antiadherence of bacteria to epithelial cells, which is a prerequisite for colonisation and infection of many pathogens. Antimicrobial berry compounds may have important applications in the future as natural antimicrobial agents for food industry as well as for medicine. Some of the novel approaches are discussed.


Similar content being viewed by others
References
Akiyama H, Fujii K, Yamasaki O, Oono T, Iwatsuki K (2001) Antibacterial action of several tannins against Staphylococcus aureus. J Antimicrob Chemother 48:487–491
Alakomi H-L, Skyttä E, Saarela M, Mattila-Sandholm T, Latva-Kala K, Helander IM (2000) Lactic acid permeabilizes gram-negative bacteria by disrupting the outer membrane. Appl Environ Microbiol 66:2001–2005
Alakomi H-L, Saarela M, Helander I (2003) Effect of EDTA on Salmonella enterica serovar Typhimurium involves a component not assignable to lipopolysaccharide release. Microbiology 149:2015–2021
Alberto MR, Farias ME, Manca de Nadra MC (2001) Effect of gallic acid and cathechin on Lactobacillus hilgardii 5w growth and metabolism of organic compounds. J Agric Food Chem 49:4359–4363
Aruoma OI, Murcia A, Butler J, Halliwell B (1993) Evaluation of the antioxidant and prooxidant actions of gallic acid and its derivatives. J Agric Food Chem 41:1880–1885
Audia JP, Webb CC, Foster JW (2001) Breaking through the acid barrier: an orchestrated response to proton stress by enteric bacteria. Int J Med Microbiol 291:97–106
Barber MS, McConnell VS, DeCaux B (2000) Antimicrobial intermediates of the general phenylpropanoid and lignin specific pathways. Phytochemistry 54:53–56
Bate-Smith EC (1973) Haemanalysis of tannins: the concept of relative astringency. Phytochemistry 12:907–912
Belofsky G, Percivill D, Lewis K, Tegos GP, Ekart J (2004) Phenolic metabolites of Dalea versicolor that enhance antibiotic activity against model pathogenic bacteria. J Nat Prod 67:481–484
Beuchat LR, Heaton EK (1975) Salmonella survival on pecan as influenced by processing and storage conditions. Appl Microbiol 29:795–801
Brul S, Coote P (1999) Preservative agents in foods. Mode of action and microbial resistance mechanisms. Int J Food Microbiol 50:1–17
Burger O, Weiss E, Sharon N, Tabak M, Neeman I, Ofek I (2002) Inhibition of Helicobacter pylori adhesion to human gastric mucus by a high-molecular-weight constituent of cranberry juice. Crit Rev Food Sci Nutr 42 [Suppl]:279–284
Burt S (2004) Essential oils: their antibacterial properties and potential applications in foods—a review. Int J Food Microbiol 94:223–253
Campos FM, Couto JA, Hogg TA (2003) Influence of phenolic acids on growth and inactivation of Oenococcus oeni and Lactobacillus hilgardii. J Appl Microbiol 94:167–174
Caturla N, Vera-Samper E, Villalain J, Mateo CR, Micol V (2003) The relationship between the antioxidant and antibacterial properties of galloylated catechins and the structure of phospholipid model membranes. Free Radical Biol Med 34:648–662
Cavanagh HM, Hipwell M, Wilkinson JM (2003) Antibacterial activity of berry fruits used for culinary purposes. J Med Food 1:57–61
Chung K-T, Stevens SE, Jr, Lin W-F, Wei CI (1993) Growth inhibition of selected food-borne bacteria by tannic acid, propyl gallate and related compounds. Lett Appl Microbiol 17:29–32
Chung K-T, Lu Z, Chou MW (1998a) Mechanism of inhibition of tannic acid and related compounds on the growth of intestinal bacteria. Food Chem Toxicol 36:1053–1060
Chung K-T, Wei C-I, Johnson MG (1998b) Are tannins a double-edged sword in biology and health? Trends Food Sci Technol 9:168–175
Cotter PD, Hill C (2003) Surviving the acid test: responses of Gram-positive bacteria to low pH. Microbiol Mol Biol Rev 67:429–453
Doores S (1993) Organic acids. In: Davidson PM, Branen AL (eds) Antimicrobials in food, 2nd edn. Marcel Dekker, New York, pp 95–136
Friedman M, Jürgens HS (2000) Effect of pH on the stability of plant phenolic compounds. J Agric Food Chem 48:2101–2110
Hada N, Kakiuchi N, Hattori M, Namba T (1989) Identification of antibacterial principles against Streptococcus mutans inhibitory principles against glucosyltransferase from the seed of Areca catechu L. Phytother Res 3:140–144
Haddock EA, Gupta RK, Al-Shafi SMK, Layden K, Haslam E, Magnolato D (1982) The metabolism of gallic acid and hexahydroxydiphenic acids in plants: Biogenetic and molecular taxonomic considerations. Phytochemistry 5:1049–1062
Harmand MF, Blanquet P (1978) The fate of total flavonolic oligomers (OFT) extracted from Vitis vinifera L. in the rat. Eur J Drug Metab Pharmacokinet 1:15–30
Haslam E (1989) Plant polyphenols: vegetable tannins revisited. Cambridge University Press, Cambridge
Hatano T, Kusuda M, Hori M, Shiota S, Tsuchiya T, Yoshida T (2003) Theasinensin A, a tea polyphenol formed from (-)-epigallocatechin gallate, suppresses antibiotic resistance of methicillin-resistant Staphylococcus aureus. Planta Med 69:984–989
Helander I, Alakomi H-L, Latva-Kala K, Mattila-Sandholm T, Pol I, Smid E, Gorris L, Wright von A (1998) Characterization of the action of selected essential oil components on gram-negative bacteria. J Agric Food Chem 46:3590–3595
Helander IM, Mattila-Sandholm T (2000) Fluorometric assessment of Gram-negative bacterial permeabilization. J Appl Microbiol 88:213–219
Herald PJ, Davidson PM (1983) Antibacterial activity of selected hydroxycinnamic acids. J Food Sci 48:1378–1379
Herrmann K (1989) Occurence and content of hydroxycinnamic and hydroxybenzoic acid compounds in foods. Crit Rev Food Sci Nutr 28:315–347
Howell AB (2002) Cranberry proanthocyanidins and the maintenance of urinary tract health. Crit Rev Food Sci Nutr 42 [Suppl]:273–278
Howell AB, Vorsa N, Marderosian AD, Foo LY (1998) Inhibition of the adherence of P-fimbriated Escherichia coli to uro-epithelial surfaces by proanthycyanidin extracts from cranberries. NE J Med 339:1085–1086
Howell AB, Leahy M, Kurowska E, Guthrie N (2001) In vivo evidence that cranberry proanthocyanidins inhibit adherence of P-fimbriated E. coli bacteria to uroepithelial cells. FASEB J 15(4):A284
Hu Z-Q, Zhao W-H, Hara Y, Shimamura T (2001) Epigallocatechin gallate synergy with ampicillin/sulbactam against 28 clinical isolates of methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother 48:361–364
Häkkinen S, Kärenlampi S, Mykkänen H, Heinonen M, Törrönen R (2000) Ellagic acid-content in berries: influence of domestic processing and storage. Eur Food Res Technol 212:75–80
Häkkinen SH, Kärenlampi SO, Heinonen MI, Mykkänen HM, Törrönen RA (1999) Content of the flavonols quercetin, myricetin, and kaempferol in 25 edible berries. J Agric Food Chem 47:2274–2279
Ikigai H, Nakae T, Hara Y, Shimamura T (1993) Bactericidal catechins damage the lipid bilayer. Biochim Biophys Acta 1147:132–136
Kolodzeij H, Kayser O, Latte KP (2003) Evaluation of the antimicrobial potency of tannins and related compounds using the microdilution broth method. Planta Med 65:444–446
Kontiokari T, Laitinen J, Järvi L, Pokka T, Sundqvist K, Uhari M (2003) Dietary factors protecting women from urinary tract infection. Am J Clin Nutr 77:600–604
Kubo I, Xiao P, Fujita K (2002) Anti-MRSA activity of alkyl gallates. Bioorg Med Chem Lett 12:113–116
Kubo I, Fujita K, Nihei K, Masuoka N (2003) Non-antibiotic antibacterial activity of dodecyl gallate. Bioorg Med Chem 11:573–580
Levy SB (2002) Active efflux, a common mechanisms for biocide and antibiotic resistance. J Appl Microbiol Symp Suppl 92:65S–71S
Maillard JY (2002) Bacterial target sites for biocide action. J Appl Microbiol Symp [Suppl] 90:16S–27S
Mazur WM, Uehara M, Wähälä K, Adlercreutz H (2000) Phyto-oestrogen content of berries, and plasma concentrations and urinary excretion of enterolactone after a single strawberry-meal in human subjects. Brit J Nutr 83:381–387
Mullen W, Stewart AJ, Lean MEJ, Gardner P, Duthie GG, Crozier A (2002) Effect of freezing and storage on the phenolics, ellagitannins, flavonoids, and antioxidant capacity of red raspberries. J Agric Food Chem 50:5197–5201
Määttä K, Kamal-Eldin A, Törrönen R (2001) Phenolic compounds in berries of black, red, green, and white currants (Ribes sp.). Antioxid Redox Sign 3:981–993
Nanayakkara NP, Burandt CL Jr, Jacob MR (2002) Flavonoids with activity against methicillin-resistant Staphylococcus aureus from Dalea scandens var. paucifolia. Planta Med 68:519–522
Nikaido H (2003) Molecular basics of bacterial outer membrane permeability revisited. Microbiol Mol Biol Rev 64:593–656
Nogueira MCL, Oyarzábal OA, Gombas DE (2003) Inactivation of Escherichia coli O157:H7, Listeria monocytogenes, and Salmonella in cranberry, lemon, and lime juice concentrates. J Food Protect 66:1637–1641
Ofek I, Goldhar J, Zafriri D, Lis H, Adar R, Sharon N (1991) Anti-Escherichia coli adhesin activity of cranberry and blueberry juices. NE J Med 324:1599
Ow YY, Stupans I (2003) Gallic acid and gallic acid derivatives: effects on drug metabolizing enzymes. Curr Drug Metab 4:241–248
Paulus W (1993) Microbicides for the protection of materials—a handbook. Chapman & Hall, London, p 496
Poole K (2004) Efflux-mediated multiresistance in Gram-negative bacteria. Clin Microbiol Infect 10:12–26
Puupponen-Pimiä R, Nohynek L, Meier C, Kähkönen M, Heinonen M, Hopia A, Oksman-Caldentey K-M (2001) Antimicrobial properties of phenolic compounds from berries. J Appl Microbiol 90:494–507
Puupponen-Pimiä R, Aura A-M, Karppinen S, Oksman-Caldentey K-M, Poutanen K (2004a) Interactions between plant bioactive food ingredients and intestinal flora—effects on human health. Biosci Microflora 23:67–80
Puupponen-Pimiä R, Nohynek L, Schmidlin S, Kähkönen M, Heinonen M, Määttä-Riihinen K, Oksman-Caldentey K-M (2004b) Berry phenolics selectively inhibit the growth of intestinal pathogens. J Appl Microbiol (in press)
Rauha J-P, Remes S, Heinonen M, Hopia A, Kähkönen M, Kujala T, Pihlaja K, Vuorela H, Vuorela P (2000) Antimicrobial effects of Finnish plant extracts containing flavonoids and other phenolic compounds. Int J Food Microbiol 56:3–12
Reed J, Howell A, Cunningham D, Krueger C (2003) Differences in structure and bacterial anti-adhesion activity of cranberry proanthocyanidins compared to proanthocyanidins from other foods. Proceedings of the 1st International conference on polyphenols and health. 18–21 November 2003, Vichy, France. Poster abstract P28
Reid G, Hsieh J, Potter P, Mighton J, Lam D, Warren D, Stephenson J (2001) Cranberry juice consumption may reduce biofilms on uroepithelial cells: Pilot study in spinal cord injured patients. Spinal Cord 39:26–30
Roccaro AS, Blanco AR, Giuliano F, Rusciano D, Enea V (2004) Epigallocatechin-gallate enhances the activity of tetracycline in staphylococci by inhibiting its efflux from bacterial cells. Antimicrob Agents Chemother 48:1968–1973
Ryan T, Wilkinson JM, Cavanagh HMA (2001) Antibacterial activity of raspberry cordial in vitro. Veter Sci 71:155–159
Scalbert A (1991) Antimicrobial properties of tannins. Phytochemistry 30:3875–3883
Sobota AE (1984) Inhibition of bacterial adherence by cranberry juice: potential use for the treatment of urinary tract infections. J Urol 131:1013–1016
Stapleton PD, Shah S, Anderson JC, Hara Y, Hamilton-Miller JMT, Taylor PW (2004) Modulation of β-lactam resistance in Staphylococcus aureus by catechins and gallates. Int J Antimicrob Agents 23:462–467
Tanaka T, Tachibana H, Nonaka B, Nishioka I, Hsu F-L, Kohda H, Tanaka O (1993) Tannins and related compounds CXXII. New dimeric, trimeric and tetrameric ellagitannins, lambertianins A-D, from Rubus lambertianus SERINGE. Chem Pharm Bull 41:1214–1220
Tegos G, Stermitz FR, Lomovskaya O, Lewis K (2002) Multidrug pump inhibitors uncover remarkable activity of plant antimicrobials. Antimicrob Agents Chemother 46:3133–3141
Toda M, Okubo S, Hiyoshi R, Shimamura T (1989) The bactericidal activity of tea and coffee. Lett Appl Microbiol 8:123–125
Törrönen R, Häkkinen S, Kärenlampi S, Mykkänen H (1997) Flavonoids and phenolic acids in selected berries. Cancer Lett 114:191–192
Ulltveit G (1998) (Wild berries) Ville baer. Technologisk forlag, 2nd edn. NW Damm, Oslo, Norway, pp 1–166
Ultee A, Bennik MHJ, Moezelaar R (2002) The phenolic hydroxyl group of carvacrol is essential for action against the food-borne pathogen Bacillus cereus. Appl Environ Microbiol 68:1561–1568
Vattem DA, Lin Y-T, Labbe RG, Shetty K (2003) Antimicrobial activity against select food-borne pathogens by phenolic antioxidants enriched in cranberry pomace by solid-state bioprocessing using the food grade fungus Rhizopus oligosporus. Process Biochem 39:1939–1946
Vattem DA, Shetty K (2003) Ellagic acid production and phenolic antioxidant activity in cranberry pomace (Vaccinium macrocarpon) mediated by Lentinus edodes using a solid-state system. Process Biochem 39:367–379
Vattem DA, Lin Y-T, Labbe RG, Shetty K (2004) Phenolic antioxidant mobilization in cranberry pomace by solid-state bioprocessing using food grade fungus Lentinus edodes and effect on antimicrobial activity against select food borne pathogens. Innovat Food Sci Emerg Technol 5:81–91
Viberg U, Sjöholm I (1996) Blåbär och lingon—bär med tradition och framtid (in Swedish). Livsmedesteknik 38:38–39
Viljakainen S (2003) Reduction of acidity in northern region berry juices. PhD Thesis, Helsinki University of Technology
Viljakainen S, Visti A, Laakso S (2002) Concentrations of organic acids and soluble sugars in juices from Nordic berries. Acta Agric Scand 52:101–109
Vivas N, Lonvaud-Funel A, Glories Y (1997) Effects of phenolic acids and anthocyanins on growth, viability and malolactic activity of a lactic acid bacterium. Food Microbiol 14:291–300
Vuorinen H, Määttä K, Törrönen R (2000) Content of the flavonols myricetin, quercetin, and kaempferol in Finnish berry wines. J Agric Food Chem 48:2675–2680
Walsh SE, Maillard JY, Russell AD, Catrenich CE, Charbonneau DL, Bartolo RG (2003) Activity and mechanisms of action of selected biocidal agents on Gram-positive and -negative bacteria. J Appl Microbiol 94:240–247
Weiss EI, Lev-Dor R, Sharon N, Ofek I (2002) Inhibitory effect of a high-molecular-weight constituent of cranberry on adhesion of oral bacteria. Crit Rev Food Sci Nutr 42 [Suppl]:285–292
Wen A, Delaquis P, Stanich K, Toivonen P (2003) Antilisterial activity of selected phenolic acids. Food Microbiol 20:305–311
Zafriri D, Ofek I, Pocino AR, Sharon N (1989) Inhibitory activity of cranberry juice on adherence of type 1 and P fimbriated Escherichia coli to eucariotic cells. Antimicrob Agents Chemother 33:92–98
Zhao W-H, Hu Z-Q, Hara Y, Shimamura T (2001a) Inhibition by epigallocatechin gallate (EGCg) of conjugative R plasmid transfer in Escherichia coli. J Infect Chemother 7:195–197
Zhao W-H, Hu Z-Q, Okubo S, Hara Y, Shimamura T (2001b) Mechanism of synergy between epigallacatechin gallate and β-lactams against methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 45:1737–1742
Zhao W-H, Asano N, Hu Z-Q, Shimamura T (2003) Restoration of antibacterial activity of β-lactams by epigallocatechin gallate against β-lactamase-producing species depending on location of β-lactamase. J Pharm Pharmacol 55:735–740
Zheng Z, Shetty K (1998) Cranberry processing waste for solid-state fungal inoculant production. Process Biochem 33:323–329
Zheng Z, Shetty K (2000) Solid-state bioconversion of phenolics from cranberry pomace and role of Letinus ododes beta-glucosidase. J Agric Food Chem 48:895–900
Yoda Y, Hu Z-Q, Zhao W-H (2004) Different susceptibilities of Staphylococcus and Gram-negative rods to epigallocatechin gallate. J Infect Chemother 10:55–58
Acknowledgements
The authors thank Professor Veli Kauppinen for his ideas and valuable discussions during the berry research at VTT. The secretarial work of Oili Lappalainen is gratefully acknowledged. Tekes, the National Technology Agency is acknowledged for financial support through the berry projects during the years 1998–2000 and 2001–2004.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Puupponen-Pimiä, R., Nohynek, L., Alakomi, HL. et al. Bioactive berry compounds—novel tools against human pathogens. Appl Microbiol Biotechnol 67, 8–18 (2005). https://doi.org/10.1007/s00253-004-1817-x
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00253-004-1817-x