Antimicrobial Capacity of Plant Polyphenols against Gram-positive Bacteria: A Comprehensive Review

Francisco    Javier    Álvarez-Martínez; Enrique       Barrajón-Catalán; José    Antonio    Encinar; Juan    Carlos    Rodríguez-Díaz; Vicente       Micol
Abstract

Background: Multi-drug-resistant bacteria such as Methicillin-Resistant Staphylococcus aureus (MRSA) disseminate rapidly amongst patients in healthcare facilities and suppose an increasingly important cause of community-associated infections and associated mortality. The development of effective therapeutic options against resistant bacteria is a public health priority. Plant polyphenols are structurally diverse compounds that have been used for centuries for medicinal purposes, including infections treatment and possess, not only antimicrobial activity, but also antioxidant, anti-inflammatory and anticancer activities among others. Based on the existing evidence on the polyphenols’ antibacterial capacity, polyphenols may be postulated as an alternative or complementary therapy for infectious diseases.
Objective: To review the antimicrobial activity of plant polyphenols against Gram-positive bacteria, especially against S. aureus and its resistant strains. Determine the main bacterial molecular targets of polyphenols and their potential mechanism of action.
Methodology: The most relevant reports on plant polyphenols’ antibacterial activity and their putative molecular targets were studied. We also performed virtual screening of thousand different polyphenols against proteins involved in the peptidoglycan biosynthesis to find potential valuable bioactive compounds. The bibliographic information used in this review was obtained from MEDLINE via PubMed.
Results: Several polyphenols: phenolic acids, flavonoids (especially flavonols), tannins, lignans, stilbenes and combinations of these in botanical mixtures, have exhibited significant antibacterial activity against resistant and non-resistant Gram-positive bacteria at low μg/mL range MIC values. Their mechanism of action is quite diverse, targeting cell wall, lipid membrane, membrane receptors and ion channels, bacteria metabolites and biofilm formation. Synergic effects were also demonstrated for some combinations of polyphenols and antibiotics.
Conclusion: Plant polyphenols mean a promising source of antibacterial agents, either alone or in combination with existing antibiotics, for the development of new antibiotic therapies.
Keywords: Antibacterial, bacterial cell wall, bacterial resistance, Gram-positive, plant polyphenols, Staphyloccocus aureus, synergy.
[1] 
Nature, E. The antibiotic alarm. Nature,  2013, 495(7440), 141.
[http://dx.doi.org/10.1038/495141a] [PMID: 23495392] 
[2] 
Torjesen, I. Antimicrobial resistance presents an “apocalyptic” threat similar to that of climate change, CMO warns. BMJ,  2013, 346, f1597.
[http://dx.doi.org/10.1136/bmj.f1597] [PMID: 23479594] 
[3] 
Shallcross, L.J.; Davies, S.C. The World Health Assembly resolution on antimicrobial resistance. J. Antimicrob. Chemother.,  2014, 69(11), 2883-2885.
[http://dx.doi.org/10.1093/jac/dku346] [PMID: 25204342] 
[4] 
Holmes, A.H.; Moore, L.S.P.; Sundsfjord, A.; Steinbakk, M.; Regmi, S.; Karkey, A.; Guerin, P.J.; Piddock, L.J.V. Understanding the mechanisms and drivers of antimicrobial resistance. Lancet,  2016, 387(10014), 176-187.
[http://dx.doi.org/10.1016/S0140-6736(15)00473-0] [PMID: 26603922] 
[5] 
Mandal, S.M.; Roy, A.; Ghosh, A.K.; Hazra, T.K.; Basak, A.; Franco, O.L. Challenges and future prospects of antibiotic therapy: from peptides to phages utilization. Front. Pharmacol.,  2014, 5, 105.
[http://dx.doi.org/10.3389/fphar.2014.00105] [PMID: 24860506] 
[6] 
Lee, C.R.; Cho, I.H.; Jeong, B.C.; Lee, S.H. Strategies to minimize antibiotic resistance. Int. J. Environ. Res. Public Health,  2013, 10(9), 4274-4305.
[http://dx.doi.org/10.3390/ijerph10094274] [PMID: 24036486] 
[7] 
Bartlett, J.G.; Gilbert, D.N.; Spellberg, B. Seven ways to preserve the miracle of antibiotics. Clin. Infect. Dis.,  2013, 56(10), 1445-1450.
[http://dx.doi.org/10.1093/cid/cit070] [PMID: 23403172] 
[8] 
McCarthy, M. Number of agents being developed to combat drug resistant bacteria is “alarmingly low,” warns report. BMJ,  2013, 346, f2548.
[http://dx.doi.org/10.1136/bmj.f2548] [PMID: 23604164] 
[9] 
Antonanzas, F.; Lozano, C.; Torres, C. Economic features of antibiotic resistance: the case of methicillin-resistant Staphylococcus aureus. Pharmacoeconomics,  2015, 33(4), 285-325.
[http://dx.doi.org/10.1007/s40273-014-0242-y] [PMID: 25447195] 
[10] 
Gudiol, F.; Aguado, J.M.; Almirante, B.; Bouza, E.; Cercenado, E.; Dominguez, M.A.; Gasch, O.; Lora-Tamayo, J.; Miro, J.M.; Palomar, M.; Pascual, A.; Pericas, J.M.; Pujol, M.; Rodriguez-Bano, J.; Shaw, E.; Soriano, A.; Valles, J. Diagnosis and treatment of bacteremia and endocarditis due to Staphylococcus aureus. A clinical guideline from the Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC). Enferm. Infecc. Microbiol. Clin.,  2015, 33(9), 621-625.
[http://dx.doi.org/10.1016/j.eimc.2015.03.014] 
[11] 
Lawes, T.; Lopez-Lozano, J-M.; Nebot, C.A.; Macartney, G.; Subbarao-Sharma, R.; Dare, C.R.J.; Wares, K.D.; Gould, I.M. Effects of national antibiotic stewardship and infection control strategies on hospital-associated and community-associated meticillin-resistant Staphylococcus aureus infections across a region of Scotland: a non-linear time-series study. Lancet Infect. Dis.,  2015, 15(12), 1438-1449.
[http://dx.doi.org/10.1016/S1473-3099(15)00315-1] [PMID: 26411518] 
[12] 
Bakthavatchalam, Y.D.; Nabarro, L.E.B.; Ralph, R.; Veeraraghavan, B. Diagnosis and management of Panton-Valentine leukocidin toxin associated Staphylococcus aureus infection: an update. Virulence,  2017, 0
[http://dx.doi.org/10.1080/21505594.2017.1362532] [PMID: 28783418] 
[13] 
Lindsay, J.A. Hospital-associated MRSA and antibiotic resistance-what have we learned from genomics? Int. J. Med. Microbiol.,  2013, 303(6-7), 318-323.
[http://dx.doi.org/10.1016/j.ijmm.2013.02.005] [PMID: 23499479] 
[14] 
Palavecino, E.L. Clinical, epidemiologic, and laboratory aspects of methicillin-resistant Staphylococcus aureus infections. Methods Mol. Biol.,  2014, 1085, 1-24.
[http://dx.doi.org/10.1007/978-1-62703-664-1_1] [PMID: 24085687] 
[15] 
Hryniewicz, M.M.; Garbacz, K. Borderline oxacillin-resistant Staphylococcus aureus (BORSA) - a more common problem than expected? J. Med. Microbiol.,  2017, 66(10), 1367-1373.
[http://dx.doi.org/10.1099/jmm.0.000585] [PMID: 28893360] 
[16] 
Chatterjee, S.S.; Chen, L.; Gilbert, A.; da Costa, T.M.; Nair, V.; Datta, S.K.; Kreiswirth, B.N.; Chambers, H.F. PBP4 Mediates β-Lactam Resistance by Altered Function. Antimicrob. Agents Chemother.,  2017, 61(11), e00932-e17.
[http://dx.doi.org/10.1128/AAC.00932-17] [PMID: 28807923] 
[17] 
Diaz, R.; Afreixo, V.; Ramalheira, E.; Rodrigues, C.; Gago, B. Evaluation of vancomycin MIC creep in methicillin-resistant Staphylococcus aureus infections-a systematic review and meta-analysis. Clin. Microbiol. Infect.,  2017, 10, 281-284.
[PMID: 28648858] 
[18] 
Stryjewski, M.E.; Corey, G.R. Methicillin-resistant Staphylococcus aureus: an evolving pathogen. Clin. Infect. Dis.,  2014, 58(Suppl. 1), S10-S19.
[http://dx.doi.org/10.1093/cid/cit613] [PMID: 24343827] 
[19] 
Musumeci, R.; Calaresu, E.; Gerosa, J.; Oggioni, D.; Bramati, S.; Morelli, P.; Mura, I.; Piana, A.; Are, B.M.; Cocuzza, C.E. Resistance to linezolid in Staphylococcus spp. clinical isolates associated with ribosomal binding site modifications: novel mutation in domain V of 23S rRNA. New Microbiol.,  2016, 39(4), 269-273.
[PMID: 27727405] 
[20] 
Rodvold, K.A.; McConeghy, K.W. Methicillin-resistant Staphylococcus aureus therapy: past, present, and future. Clin. Infect. Dis.,  2014, 58(Suppl. 1), S20-S27.
[http://dx.doi.org/10.1093/cid/cit614] [PMID: 24343828] 
[21] 
Gómez Casanova, N.; Siller Ruiz, M.; Muñoz Bellido, J.L. Mechanisms of resistance to daptomycin in Staphylococcus aureus. Rev. Esp. Quimioter.,  2017, 30(6), 391-396.
[PMID: 29082727] 
[22] 
Sader, H.S.; Farrell, D.J.; Flamm, R.K.; Jones, R.N. Activity of ceftaroline and comparator agents tested against Staphylococcus aureus from patients with bloodstream infections in US medical centres (2009-13). J. Antimicrob. Chemother.,  2015, 70(7), 2053-2056.
[http://dx.doi.org/10.1093/jac/dkv076] [PMID: 25814163] 
[23] 
Roberts, K.D.; Sulaiman, R.M.; Rybak, M.J. Dalbavancin and Oritavancin: An Innovative Approach to the Treatment of Gram-Positive Infections. Pharmacotherapy,  2015, 35(10), 935-948.
[http://dx.doi.org/10.1002/phar.1641] [PMID: 26497480] 
[24] 
Agarwal, R.; Bartsch, S.M.; Kelly, B.J.; Prewitt, M.; Liu, Y.; Chen, Y.; Umscheid, C.A. Newer glycopeptide antibiotics for treatment of complicated skin and soft tissue infections: systematic review, network meta-analysis and cost analysis. Clin. Microbiol. Infect.,  2017, 24(4), 1-8.
[PMID: 28882727] 
[25] 
Wink, M. Modes of Action of Herbal Medicines and Plant Secondary Metabolites. Medicines (Basel),  2015, 2(3), 251-286.
[http://dx.doi.org/10.3390/medicines2030251] [PMID: 28930211] 
[26] 
Wink, M.; Ashour, M.L.; El-Readi, M.Z. Secondary Metabolites from Plants Inhibiting ABC Transporters and Reversing Resistance of Cancer Cells and Microbes to Cytotoxic and Antimicrobial Agents. Front. Microbiol.,  2012, 3, 130.
[http://dx.doi.org/10.3389/fmicb.2012.00130] [PMID: 22536197] 
[27] 
Lamming, D.W.; Wood, J.G.; Sinclair, D.A. Small molecules that regulate lifespan: evidence for xenohormesis. Mol. Microbiol.,  2004, 53(4), 1003-1009.
[http://dx.doi.org/10.1111/j.1365-2958.2004.04209.x] [PMID: 15306006] 
[28] 
Dixon, R.A. Natural products and plant disease resistance. Nature,  2001, 411(6839), 843-847.
[http://dx.doi.org/10.1038/35081178] [PMID: 11459067] 
[29] 
Stevenson, D.E.; Hurst, R.D. Polyphenolic phytochemicals--just antioxidants or much more? Cell. Mol. Life Sci.,  2007, 64(22), 2900-2916.
[http://dx.doi.org/10.1007/s00018-007-7237-1] [PMID: 17726576] 
[30] 
Barrajón-Catalán, E.; Herranz-López, M.; Joven, J.; Segura-Carretero, A.; Alonso-Villaverde, C.; Menéndez, J.A.; Micol, V. Molecular promiscuity of plant polyphenols in the management of age-related diseases: far beyond their antioxidant properties. Adv. Exp. Med. Biol.,  2014, 824, 141-159.
[http://dx.doi.org/10.1007/978-3-319-07320-0_11] [PMID: 25038998] 
[31] 
Herranz-López, M.; Olivares-Vicente, M.; Encinar, J.A.; Barrajón-Catalán, E.; Segura-Carretero, A.; Joven, J.; Micol, V. Multi-Targeted Molecular Effects of Hibiscus sabdariffa Polyphenols: An Opportunity for a Global Approach to Obesity. Nutrients,  2017, 9(8), E907
[http://dx.doi.org/10.3390/nu9080907] [PMID: 28825642] 
[32] 
Howitz, K.T.; Sinclair, D.A. Xenohormesis: sensing the chemical cues of other species. Cell,  2008, 133(3), 387-391.
[http://dx.doi.org/10.1016/j.cell.2008.04.019] [PMID: 18455976] 
[33] 
Fernández-Arroyo, S.; Herranz-López, M.; Beltrán-Debón, R.; Borrás-Linares, I.; Barrajón-Catalán, E.; Joven, J.; Fernández-Gutiérrez, A.; Segura-Carretero, A.; Micol, V. Bioavailability study of a polyphenol-enriched extract from Hibiscus sabdariffa in rats and associated antioxidant status. Mol. Nutr. Food Res.,  2012, 56(10), 1590-1595.
[http://dx.doi.org/10.1002/mnfr.201200091] [PMID: 22893520] 
[34] 
Olivares-Vicente, M.; Barrajon-Catalan, E.; Herranz-Lopez, M.; Segura-Carretero, A.; Joven, J.; Encinar, J.A.; Micol, V. Plant-derived polyphenols in human health: biological activity, metabolites and putative molecular targets. Curr. Drug Metab.,  2018, 19(4), 351-369.
[http://dx.doi.org/10.2174/1389200219666180220095236] [PMID: 29468962] 
[35] 
Fu, J.; Wu, S.; Wang, M.; Tian, Y.; Zhang, Z.; Song, R. Intestinal metabolism of Polygonum cuspidatum in vitro and in vivo. Biomed. Chromatogr.,  2018, 32(6), e4190
[http://dx.doi.org/10.1002/bmc.4190] [PMID: 29334690] 
[36] 
Marín, L.; Miguélez, E.M.; Villar, C.J.; Lombó, F. Bioavailability of dietary polyphenols and gut microbiota metabolism: antimicrobial properties. BioMed Res. Int.,  2015, 2015905215
[http://dx.doi.org/10.1155/2015/905215] [PMID: 25802870] 
[37] 
de Camargo, A.C.; Regitano-d’Arce, M.A.B.; Rasera, G.B.; Canniatti-Brazaca, S.G.; do Prado-Silva, L.; Alvarenga, V.O.; Sant’Ana, A.S.; Shahidi, F. Phenolic acids and flavonoids of peanut by-products: Antioxidant capacity and antimicrobial effects. Food Chem.,  2017, 237, 538-544.
[http://dx.doi.org/10.1016/j.foodchem.2017.05.046] [PMID: 28764032] 
[38] 
Zengin, G.; Uysal, A.; Aktumsek, A.; Mocan, A.; Mollica, A.; Locatelli, M.; Custodio, L.; Neng, N.R.; Nogueira, J.M.F.; Aumeeruddy-Elalfi, Z.; Mahomoodally, M.F. Euphorbia denticulata Lam.: A promising source of phyto-pharmaceuticals for the development of novel functional formulations. Biomed. Pharmacother.,  2017, 87, 27-36.
[http://dx.doi.org/10.1016/j.biopha.2016.12.063] [PMID: 28040595] 
[39] 
Barber, M.S.; McConnell, V.S.; DeCaux, B.S. Antimicrobial intermediates of the general phenylpropanoid and lignin specific pathways. Phytochemistry,  2000, 54(1), 53-56.
[http://dx.doi.org/10.1016/S0031-9422(00)00038-8] [PMID: 10846747] 
[40] 
Bag, A.; Chattopadhyay, R.R. Synergistic antibacterial and antibiofilm efficacy of nisin in combination with p-coumaric acid against food-borne bacteria Bacillus cereus and Salmonella typhimurium. Lett. Appl. Microbiol.,  2017, 65(5), 366-372.
[http://dx.doi.org/10.1111/lam.12793] [PMID: 28815637] 
[41] 
Garcia-Muñoz, C.; Vaillant, F. Metabolic fate of ellagitannins: implications for health, and research perspectives for innovative functional foods. Crit. Rev. Food Sci. Nutr.,  2014, 54(12), 1584-1598.
[http://dx.doi.org/10.1080/10408398.2011.644643] [PMID: 24580560] 
[42] 
Clifford, M.; Scalbert, A. Ellagitannins – nature, occurrence and dietary burden.pdf. J. Food Sci. Agric,  2000, 80(7)
[43] 
Shimozu, Y.; Kuroda, T.; Tsuchiya, T.; Hatano, T. Structures and Antibacterial Properties of Isorugosins H-J, Oligomeric Ellagitannins from Liquidambar formosana with Characteristic Bridging Groups between Sugar Moieties. J. Nat. Prod.,  2017, 80(10), 2723-2733.
[http://dx.doi.org/10.1021/acs.jnatprod.7b00496] [PMID: 29019685] 
[44] 
Okuda, T.; Yoshida, T.; Hatano, T. Ellagitannins as active constituents of medicinal plants. Planta Med.,  1989, 55(2), 117-122.
[http://dx.doi.org/10.1055/s-2006-961902] [PMID: 2664829] 
[45] 
González, M.J.; Torres, J.L.; Medina, I. Impact of thermal processing on the activity of gallotannins and condensed tannins from Hamamelis virginiana used as functional ingredients in seafood. J. Agric. Food Chem.,  2010, 58(7), 4274-4283.
[http://dx.doi.org/10.1021/jf904032y] [PMID: 20222659] 
[46] 
Gan, R.Y.; Kong, K.W.; Li, H.B.; Wu, K.; Ge, Y.Y.; Chan, C.L.; Shi, X.M.; Corke, H. Separation, Identification, and Bioactivities of the Main Gallotannins of Red Sword Bean (Canavalia gladiata) Coats. Front Chem.,  2018, 6, 39.
[http://dx.doi.org/10.3389/fchem.2018.00039] [PMID: 29541634] 
[47] 
Barrajón-Catalán, E.; Fernández-Arroyo, S.; Saura, D.; Guillén, E.; Fernández-Gutiérrez, A.; Segura-Carretero, A.; Micol, V. Cistaceae aqueous extracts containing ellagitannins show antioxidant and antimicrobial capacity, and cytotoxic activity against human cancer cells. Food Chem. Toxicol.,  2010, 48(8-9), 2273-2282.
[http://dx.doi.org/10.1016/j.fct.2010.05.060] [PMID: 20510328] 
[48] 
Tomás-Menor, L.; Morales-Soto, A.; Barrajón-Catalán, E.; Roldán-Segura, C.; Segura-Carretero, A.; Micol, V. Correlation between the antibacterial activity and the composition of extracts derived from various Spanish Cistus species. Food Chem. Toxicol.,  2013, 55, 313-322.
[http://dx.doi.org/10.1016/j.fct.2013.01.006] [PMID: 23333717] 
[49] 
Shimozu, Y.; Kimura, Y.; Esumi, A.; Aoyama, H.; Kuroda, T.; Sakagami, H.; Hatano, T. Ellagitannins of Davidia involucrata. I. Structure of Davicratinic Acid A and Effects of Davidia Tannins on Drug-Resistant Bacteria and Human Oral Squamous Cell Carcinomas. Molecules,  2017, 22(3), E470
[http://dx.doi.org/10.3390/molecules22030470] [PMID: 28294988] 
[50] 
Tomás-Menor, L.; Barrajón-Catalán, E.; Segura-Carretero, A.; Martí, N.; Saura, D.; Menéndez, J.A.; Joven, J.; Micol, V. The promiscuous and synergic molecular interaction of polyphenols in bactericidal activity: an opportunity to improve the performance of antibiotics? Phytother. Res.,  2015, 29(3), 466-473.
[http://dx.doi.org/10.1002/ptr.5296] [PMID: 25625775] 
[51] 
Lee, C.J.; Chen, L.G.; Liang, W.L.; Wang, C.C. Multiple Activities of Punica granatum Linne against Acne Vulgaris. Int. J. Mol. Sci.,  2017, 18(1), E141
[http://dx.doi.org/10.3390/ijms18010141] [PMID: 28085116] 
[52] 
Engels, C.; Schieber, A.; Gänzle, M.G. Inhibitory spectra and modes of antimicrobial action of gallotannins from mango kernels (Mangifera indica L.). Appl. Environ. Microbiol.,  2011, 77(7), 2215-2223.
[http://dx.doi.org/10.1128/AEM.02521-10] [PMID: 21317249] 
[53] 
Henis, Y.; Tagari, H.; Volcani, R. Effect of water extracts of carob pods, tannic acid, and their derivatives on the morphology and growth of microorganisms. Appl. Microbiol.,  1964, 12(3), 204-209.
[http://dx.doi.org/10.1128/AEM.12.3.204-209.1964] [PMID: 14170956] 
[54] 
Kozłowska, A.; Szostak-Węgierek, D. Flavonoids--food sources and health benefits. Rocz. Panstw. Zakl. Hig.,  2014, 65(2), 79-85.
[PMID: 25272572] 
[55] 
Fazly Bazzaz, B.S.; Sarabandi, S.; Khameneh, B.; Hosseinzadeh, H. Effect of Catechins, Green tea Extract and Methylxanthines in Combination with Gentamicin Against Staphylococcus aureus and Pseudomonas aeruginosa: - Combination therapy against resistant bacteria. J. Pharmacopuncture,  2016, 19(4), 312-318.
[http://dx.doi.org/10.3831/KPI.2016.19.032] [PMID: 28097041] 
[56] 
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(18), 3111-3116.
[http://dx.doi.org/10.1016/j.phytochem.2007.08.013] [PMID: 17889045] 
[57] 
Sharma, A.; Gupta, S.; Sarethy, I.P.; Dang, S.; Gabrani, R. Green tea extract: possible mechanism and antibacterial activity on skin pathogens. Food Chem.,  2012, 135(2), 672-675.
[http://dx.doi.org/10.1016/j.foodchem.2012.04.143] [PMID: 22868144] 
[58] 
Hatano, T.; Kusuda, M.; Inada, K.; Ogawa, T.O.; Shiota, S.; Tsuchiya, T.; Yoshida, T. Effects of tannins and related polyphenols on methicillin-resistant Staphylococcus aureus. Phytochemistry,  2005, 66(17), 2047-2055.
[http://dx.doi.org/10.1016/j.phytochem.2005.01.013] [PMID: 16153408] 
[59] 
Khoo, H.E.; Azlan, A.; Tang, S.T.; Lim, S.M. Anthocyanidins and anthocyanins: colored pigments as food, pharmaceutical ingredients, and the potential health benefits. Food Nutr. Res.,  2017, 61(1), 1361779
[http://dx.doi.org/10.1080/16546628.2017.1361779] [PMID: 28970777] 
[60] 
Lacombe, A.; Wu, V.C.; Tyler, S.; Edwards, K. Antimicrobial action of the American cranberry constituents; phenolics, anthocyanins, and organic acids, against Escherichia coli O157:H7. Int. J. Food Microbiol.,  2010, 139(1-2), 102-107.
[http://dx.doi.org/10.1016/j.ijfoodmicro.2010.01.035] [PMID: 20153540] 
[61] 
Naz, S.; Siddiqi, R.; Ahmad, S.; Rasool, S.A.; Sayeed, S.A. Antibacterial activity directed isolation of compounds from Punica granatum. J. Food Sci.,  2007, 72(9), M341-M345.
[http://dx.doi.org/10.1111/j.1750-3841.2007.00533.x] [PMID: 18034726] 
[62] 
Puupponen-Pimiä, R.; Nohynek, L.; Alakomi, H.L.; Oksman-Caldentey, K.M. The action of berry phenolics against human intestinal pathogens. Biofactors,  2005, 23(4), 243-251.
[http://dx.doi.org/10.1002/biof.5520230410] [PMID: 16498212] 
[63] 
Barreca, D.; Gattuso, G.; Bellocco, E.; Calderaro, A.; Trombetta, D.; Smeriglio, A.; Laganà, G.; Daglia, M.; Meneghini, S.; Nabavi, S.M. Flavanones: Citrus phytochemical with health-promoting properties. Biofactors,  2017, 43(4), 495-506.
[http://dx.doi.org/10.1002/biof.1363] [PMID: 28497905] 
[64] 
Siriwong, S.; Teethaisong, Y.; Thumanu, K.; Dunkhunthod, B.; Eumkeb, G. The synergy and mode of action of quercetin plus amoxicillin against amoxicillin-resistant Staphylococcus epidermidis. BMC Pharmacol. Toxicol.,  2016, 17(1), 39.
[http://dx.doi.org/10.1186/s40360-016-0083-8] [PMID: 27491399] 
[65] 
Mokhtar, M.; Ginestra, G.; Youcefi, F.; Filocamo, A.; Bisignano, C.; Riazi, A. Antimicrobial Activity of Selected Polyphenols and Capsaicinoids Identified in Pepper (Capsicum annuum L.) and Their Possible Mode of Interaction. Curr. Microbiol.,  2017, 74(11), 1253-1260.
[http://dx.doi.org/10.1007/s00284-017-1310-2] [PMID: 28721659] 
[66] 
Su, Y.; Ma, L.; Wen, Y.; Wang, H.; Zhang, S. Studies of the in vitro antibacterial activities of several polyphenols against clinical isolates of methicillin-resistant Staphylococcus aureus. Molecules,  2014, 19(8), 12630-12639.
[http://dx.doi.org/10.3390/molecules190812630] [PMID: 25153875] 
[67] 
Madikizela, B.; Aderogba, M.A.; Van Staden, J. Isolation and characterization of antimicrobial constituents of Searsia chirindensis L. (Anacardiaceae) leaf extracts. J. Ethnopharmacol.,  2013, 150(2), 609-613.
[http://dx.doi.org/10.1016/j.jep.2013.09.016] [PMID: 24060408] 
[68] 
Zhang, Y.; Wang, J.F.; Dong, J.; Wei, J.Y.; Wang, Y.N.; Dai, X.H.; Wang, X.; Luo, M.J.; Tan, W.; Deng, X.M.; Niu, X.D. Inhibition of α-toxin production by subinhibitory concentrations of naringenin controls Staphylococcus aureus pneumonia. Fitoterapia,  2013, 86, 92-99.
[http://dx.doi.org/10.1016/j.fitote.2013.02.001] [PMID: 23425602] 
[69] 
Céliz, G.; Daz, M.; Audisio, M.C. Antibacterial activity of naringin derivatives against pathogenic strains. J. Appl. Microbiol.,  2011, 111(3), 731-738.
[http://dx.doi.org/10.1111/j.1365-2672.2011.05070.x] [PMID: 21672094] 
[70] 
Sato, Y.; Suzaki, S.; Nishikawa, T.; Kihara, M.; Shibata, H.; Higuti, T. Phytochemical flavones isolated from Scutellaria barbata and antibacterial activity against methicillin-resistant Staphylococcus aureus. J. Ethnopharmacol.,  2000, 72(3), 483-488.
[http://dx.doi.org/10.1016/S0378-8741(00)00265-8] [PMID: 10996290] 
[71] 
Chang, P.C.; Li, H.Y.; Tang, H.J.; Liu, J.W.; Wang, J.J.; Chuang, Y.C. In vitro synergy of baicalein and gentamicin against vancomycin-resistant Enterococcus. J. Microbiol. Immunol. Infect.,  2007, 40(1), 56-61.
[PMID: 17332908] 
[72] 
Fujita, M.; Shiota, S.; Kuroda, T.; Hatano, T.; Yoshida, T.; Mizushima, T.; Tsuchiya, T. Remarkable synergies between baicalein and tetracycline, and baicalein and beta-lactams against methicillin-resistant Staphylococcus aureus. Microbiol. Immunol.,  2005, 49(4), 391-396.
[http://dx.doi.org/10.1111/j.1348-0421.2005.tb03732.x] [PMID: 15840965] 
[73] 
Wang, T.; Liu, Y.; Li, X.; Xu, Q.; Feng, Y.; Yang, S. Isoflavones from green vegetable soya beans and their antimicrobial and antioxidant activities. J. Sci. Food Agric., 2017.
[PMID: 28885710] 
[74] 
Su, S.; Wink, M. Natural lignans from Arctium lappa as antiaging agents in Caenorhabditis elegans. Phytochemistry,  2015, 117, 340-350.
[http://dx.doi.org/10.1016/j.phytochem.2015.06.021] [PMID: 26141518] 
[75] 
Peterson, J.; Dwyer, J.; Adlercreutz, H.; Scalbert, A.; Jacques, P.; McCullough, M.L. Dietary lignans: physiology and potential for cardiovascular disease risk reduction. Nutr. Rev.,  2010, 68(10), 571-603.
[http://dx.doi.org/10.1111/j.1753-4887.2010.00319.x] [PMID: 20883417] 
[76] 
Laporta, O.; Funes, L.; Garzón, M.T.; Villalaín, J.; Micol, V. Role of membranes on the antibacterial and anti-inflammatory activities of the bioactive compounds from Hypoxis rooperi corm extract. Arch. Biochem. Biophys.,  2007, 467(1), 119-131.
[http://dx.doi.org/10.1016/j.abb.2007.08.013] [PMID: 17888867] 
[77] 
Zuo, G.Y.; Zhang, X.J.; Han, J.; Li, Y.Q.; Wang, G.C. In vitro synergism of magnolol and honokiol in combination with antibacterial agents against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). BMC Complement. Altern. Med.,  2015, 15, 425.
[http://dx.doi.org/10.1186/s12906-015-0938-3] [PMID: 26627468] 
[78] 
Zhang, J.; Chen, J.; Liang, Z.; Zhao, C. New lignans and their biological activities. Chem. Biodivers.,  2014, 11(1), 1-54.
[http://dx.doi.org/10.1002/cbdv.201100433] [PMID: 24443425] 
[79] 
Li, C.; Liu, H.; Zhao, L.; Zhang, W.; Qiu, S.; Yang, X.; Tan, H. Antibacterial neolignans from the leaves of Melaleuca bracteata. Fitoterapia,  2017, 120, 171-176.
[http://dx.doi.org/10.1016/j.fitote.2017.06.015] [PMID: 28625731] 
[80] 
Maruyama, M.; Yamauchi, S.; Akiyama, K.; Sugahara, T.; Kishida, T.; Koba, Y. Antibacterial activity of a virgatusin-related compound. Biosci. Biotechnol. Biochem.,  2007, 71(3), 677-680.
[http://dx.doi.org/10.1271/bbb.60429] [PMID: 17341839] 
[81] 
Bostanghadiri, N.; Pormohammad, A.; Chirani, A.S.; Pouriran, R.; Erfanimanesh, S.; Hashemi, A. Comprehensive review on the antimicrobial potency of the plant polyphenol Resveratrol. Biomed. Pharmacother.,  2017, 95, 1588-1595.
[http://dx.doi.org/10.1016/j.biopha.2017.09.084] [PMID: 28950659] 
[82] 
Martin, D.A.; Bolling, B.W. A review of the efficacy of dietary polyphenols in experimental models of inflammatory bowel diseases. Food Funct.,  2015, 6(6), 1773-1786.
[http://dx.doi.org/10.1039/C5FO00202H] [PMID: 25986932] 
[83] 
Kumar, S.N.; Siji, J.V.; Rajasekharan, K.N.; Nambisan, B.; Mohandas, C. Bioactive stilbenes from a Bacillus sp. N strain associated with a novel rhabditid entomopathogenic nematode. Lett. Appl. Microbiol.,  2012, 54(5), 410-417.
[http://dx.doi.org/10.1111/j.1472-765X.2012.03223.x] [PMID: 22332977] 
[84] 
Lee, K.; Lee, J.H.; Ryu, S.Y.; Cho, M.H.; Lee, J. Stilbenes reduce Staphylococcus aureus hemolysis, biofilm formation, and virulence. Foodborne Pathog. Dis.,  2014, 11(9), 710-717.
[http://dx.doi.org/10.1089/fpd.2014.1758] [PMID: 25007234] 
[85] 
Sun, D.; Hurdle, J.G.; Lee, R.; Lee, R.; Cushman, M.; Pezzuto, J.M. Evaluation of flavonoid and resveratrol chemical libraries reveals abyssinone II as a promising antibacterial lead. ChemMedChem,  2012, 7(9), 1541-1545.
[http://dx.doi.org/10.1002/cmdc.201200253] [PMID: 22847956] 
[86] 
Lee, W.X.; Basri, D.F.; Ghazali, A.R. Bactericidal Effect of Pterostilbene Alone and in Combination with Gentamicin against Human Pathogenic Bacteria. Molecules,  2017, 22(3), E463
[http://dx.doi.org/10.3390/molecules22030463] [PMID: 28304328] 
[87] 
Araya-Cloutier, C.; den Besten, H.M.; Aisyah, S.; Gruppen, H.; Vincken, J.P. The position of prenylation of isoflavonoids and stilbenoids from legumes (Fabaceae) modulates the antimicrobial activity against Gram positive pathogens. Food Chem.,  2017, 226, 193-201.
[http://dx.doi.org/10.1016/j.foodchem.2017.01.026] [PMID: 28254012] 
[88] 
Reygaert, W.C. The antimicrobial possibilities of green tea. Front. Microbiol.,  2014, 5, 434.
[http://dx.doi.org/10.3389/fmicb.2014.00434] [PMID: 25191312] 
[89] 
Taylor, P.W.; Hamilton-Miller, J.M.; Stapleton, P.D. Antimicrobial properties of green tea catechins. Food Sci. Technol. Bull.,  2005, 2, 71-81.
[http://dx.doi.org/10.1616/1476-2137.14184] [PMID: 19844590] 
[90] 
Tyc, O.; Tomás-Menor, L.; Garbeva, P.; Barrajón-Catalán, E.; Micol, V. Validation of the AlamarBlue® Assay as a Fast Screening Method to Determine the Antimicrobial Activity of Botanical Extracts. PLoS One,  2016, 11(12), e0169090
[http://dx.doi.org/10.1371/journal.pone.0169090] [PMID: 28033417] 
[91] 
Sahli, R.; Rivière, C.; Neut, C.; Bero, J.; Sahuc, M.E.; Smaoui, A.; Beaufay, C.; Roumy, V.; Hennebelle, T.; Rouillé, Y.; Quetin-Leclercq, J.; Séron, K.; Ksouri, R.; Sahpaz, S. An ecological approach to discover new bioactive extracts and products: the case of extremophile plants. J. Pharm. Pharmacol.,  2017, 69(8), 1041-1055.
[http://dx.doi.org/10.1111/jphp.12728] [PMID: 28444868] 
[92] 
Dickson, R.A.; Houghton, P.J.; Hylands, P.J.; 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), 41-45.
[http://dx.doi.org/10.1002/ptr.1799] [PMID: 16397919] 
[93] 
Munyendo, W.L.L.; Orwa, J.A.; Rukunga, G.M.; Bii, C.C. Bacteriostatic and Bactericidal Activities of Aspilia mossambicensis, Ocimum gratissimum and Toddalia asiatica Extracts on Selected Pathogenic Bacteria. Res. J. Med. Plant,  2011, 5(6), 717-727.
[http://dx.doi.org/10.3923/rjmp.2011.717.727] 
[94] 
Abdul Qadir, M.; Shahzadi, S.K.; Bashir, A.; Munir, A.; Shahzad, S. Evaluation of Phenolic Compounds and Antioxidant and Antimicrobial Activities of Some Common Herbs. Int. J. Anal. Chem.,  2017, 20173475738
[http://dx.doi.org/10.1155/2017/3475738] [PMID: 28316626] 
[95] 
Howell, A.B.; D’Souza, D.H. The pomegranate: effects on bacteria and viruses that influence human health. Evid. Based Complement. Alternat. Med.,  2013, 2013606212
[http://dx.doi.org/10.1155/2013/606212] [PMID: 23762148] 
[96] 
Braga, L.C.; Leite, A.A.; Xavier, K.G.; Takahashi, J.A.; Bemquerer, M.P.; Chartone-Souza, E.; Nascimento, A.M. Synergic interaction between pomegranate extract and antibiotics against Staphylococcus aureus. Can. J. Microbiol.,  2005, 51(7), 541-547.
[http://dx.doi.org/10.1139/w05-022] [PMID: 16175202] 
[97] 
Voravuthikunchai, S.P.; Kitpipit, L. Activity of medicinal plant extracts against hospital isolates of methicillin-resistant Staphylococcus aureus. Clin. Microbiol. Infect.,  2005, 11(6), 510-512.
[http://dx.doi.org/10.1111/j.1469-0691.2005.01104.x] [PMID: 15882206] 
[98] 
Su, X.; Howell, A.B.; D’Souza, D.H. Antibacterial effects of plant-derived extracts on methicillin-resistant Staphylococcus aureus. Foodborne Pathog. Dis.,  2012, 9(6), 573-578.
[http://dx.doi.org/10.1089/fpd.2011.1046] [PMID: 22663188] 
[99] 
European Committee for Antimicrobial Susceptibility Testing (EUCAST) of the European Society of Clinical Microbiology and Infectious Dieases. (ESCMID). EUCAST Definitive Document E.Def 1.2, May 2000: Terminology relating to methods for the determination of susceptibility of bacteria to antimicrobial agents. Clin. Microbiol. Infect.,  2000, 6(9), 503-508.
[http://dx.doi.org/10.1046/j.1469-0691.2000.00149.x] [PMID: 11168186] 
[100] 
Solarte, A.L.; Astorga, R.J.; Aguiar, F.; Galán-Relaño, Á.; Maldonado, A.; Huerta, B. Combination of Antimicrobials and Essential Oils as an Alternative for the Control of Salmonella enterica Multiresistant Strains Related to Foodborne Disease. Foodborne Pathog. Dis.,  2017, 14(10), 558-563.
[http://dx.doi.org/10.1089/fpd.2017.2295] [PMID: 28683217] 
[101] 
Gómez Castellanos, J.R.; Prieto, J.M.; Heinrich, M. Red Lapacho (Tabebuia impetiginosa)--a global ethnopharmacological commodity? J. Ethnopharmacol.,  2009, 121(1), 1-13.
[http://dx.doi.org/10.1016/j.jep.2008.10.004] [PMID: 18992801] 
[102] 
Wagner, H.; Ulrich-Merzenich, G. Synergy research: approaching a new generation of phytopharmaceuticals. Phytomedicine,  2009, 16(2-3), 97-110.
[http://dx.doi.org/10.1016/j.phymed.2008.12.018] [PMID: 19211237] 
[103] 
Arima, H.; Ashida, H.; Danno, G. Rutin-enhanced antibacterial activities of flavonoids against Bacillus cereus and Salmonella enteritidis. Biosci. Biotechnol. Biochem.,  2002, 66(5), 1009-1014.
[http://dx.doi.org/10.1271/bbb.66.1009] [PMID: 12092809] 
[104] 
Ganeshpurkar, A.; Saluja, A.K. The Pharmacological Potential of Rutin. Saudi Pharm. J.,  2017, 25(2), 149-164.
[http://dx.doi.org/10.1016/j.jsps.2016.04.025] [PMID: 28344465] 
[105] 
Tegos, G.; Stermitz, F.R.; Lomovskaya, O.; Lewis, K. Multidrug pump inhibitors uncover remarkable activity of plant antimicrobials. Antimicrob. Agents Chemother.,  2002, 46(10), 3133-3141.
[http://dx.doi.org/10.1128/AAC.46.10.3133-3141.2002] [PMID: 12234835] 
[106] 
Kwon, Y.I.; Apostolidis, E.; Labbe, R.G.; Shetty, K. Inhibition of Staphylococcus aureus by Phenolic Phytochemicals of Selected Clonal Herbs Species of Lamiaceae Family and Likely Mode of Action through Proline Oxidation. Food Biotechnol.,  2007, 21(1), 71-89.
[http://dx.doi.org/10.1080/08905430701191205] 
[107] 
Betoni, J.E.; Mantovani, R.P.; Barbosa, L.N.; Di Stasi, L.C.; Fernandes, Junior, A. Synergism between plant extract and antimicrobial drugs used on Staphylococcus aureus diseases. Mem. Inst. Oswaldo Cruz,  2006, 101(4), 387-390.
[http://dx.doi.org/10.1590/S0074-02762006000400007] [PMID: 16951808] 
[108] 
Sudano Roccaro, A.; Blanco, A.R.; Giuliano, F.; Rusciano, D.; Enea, V. Epigallocatechin-gallate enhances the activity of tetracycline in staphylococci by inhibiting its efflux from bacterial cells. Antimicrob. Agents Chemother.,  2004, 48(6), 1968-1973.
[http://dx.doi.org/10.1128/AAC.48.6.1968-1973.2004] [PMID: 15155186] 
[109] 
Stapleton, P.D.; Shah, S.; Hara, Y.; Taylor, P.W. Potentiation of catechin gallate-mediated sensitization of Staphylococcus aureus to oxacillin by nongalloylated catechins. Antimicrob. Agents Chemother.,  2006, 50(2), 752-755.
[http://dx.doi.org/10.1128/AAC.50.2.752-755.2006] [PMID: 16436737] 
[110] 
Stapleton, P.D.; Shah, S.; Anderson, J.C.; Hara, Y.; Hamilton-Miller, J.M.; Taylor, P.W. Modulation of beta-lactam resistance in Staphylococcus aureus by catechins and gallates. Int. J. Antimicrob. Agents,  2004, 23(5), 462-467.
[http://dx.doi.org/10.1016/j.ijantimicag.2003.09.027] [PMID: 15120724] 
[111] 
Kim, S.Y.; Kim, J.; Jeong, S.I.; Jahng, K.Y.; Yu, K.Y. Antimicrobial Effects and Resistant Regulation of Magnolol and Honokiol on Methicillin-Resistant Staphylococcus aureus. BioMed Res. Int.,  2015, 2015283630
[http://dx.doi.org/10.1155/2015/283630] [PMID: 26357651] 
[112] 
Shiota, S.; Shimizu, M.; Sugiyama, J.; Morita, Y.; Mizushima, T.; Tsuchiya, T. Mechanisms of action of corilagin and tellimagrandin I that remarkably potentiate the activity of beta-lactams against methicillin-resistant Staphylococcus aureus. Microbiol. Immunol.,  2004, 48(1), 67-73.
[http://dx.doi.org/10.1111/j.1348-0421.2004.tb03489.x] [PMID: 14734860] 
[113] 
Morel, C.; Stermitz, F.R.; Tegos, G.; Lewis, K. Isoflavones as potentiators of antibacterial activity. J. Agric. Food Chem.,  2003, 51(19), 5677-5679.
[http://dx.doi.org/10.1021/jf0302714] [PMID: 12952418] 
[114] 
Santiago, C.; Pang, E.L.; Lim, K.H.; Loh, H.S.; Ting, K.N. Inhibition of penicillin-binding protein 2a (PBP2a) in methicillin resistant Staphylococcus aureus (MRSA) by combination of ampicillin and a bioactive fraction from Duabanga grandiflora. BMC Complement. Altern. Med.,  2015, 15, 178.
[http://dx.doi.org/10.1186/s12906-015-0699-z] [PMID: 26060128] 
[115] 
Hu, D.L.; Nakane, A. Mechanisms of staphylococcal enterotoxin-induced emesis. Eur. J. Pharmacol.,  2014, 722, 95-107.
[http://dx.doi.org/10.1016/j.ejphar.2013.08.050] [PMID: 24184671] 
[116] 
Martillanes, S.; Rocha-Pimienta, J.; Cabrera-Bañegil, M.; Martín-Vertedor, D.; Delgado-Adámez, J. Phenolic Compounds
 - Biological Activity; Soto-Hernandez, M.; Palma-
 Tenango, M.; Garcia-Mateos, M.R., Eds.; InTech: Rijeka . , 2017.  p. 3.
[117] 
Zhao, Y.; Zhu, A.; Tang, J.; Tang, C.; Chen, J. Comparative Effects of Food Preservatives on the Production of Staphylococcal Enterotoxin I from Staphylococcus aureus Isolate. J. Food Qual.,  2017, 2017, 5.
[http://dx.doi.org/10.1155/2017/9495314] 
[118] 
Shimamura, Y.; Hirai, C.; Sugiyama, Y.; Shibata, M.; Ozaki, J.; Murata, M.; Ohashi, N.; Masuda, S. Inhibitory effects of food additives derived from polyphenols on staphylococcal enterotoxin A production and biofilm formation by Staphylococcus aureus. Biosci. Biotechnol. Biochem.,  2017, 81(12), 2346-2352.
[http://dx.doi.org/10.1080/09168451.2017.1395681] [PMID: 29098937] 
[119] 
Maqsood, S.; Benjakul, S.; Shahidi, F. Emerging role of phenolic compounds as natural food additives in fish and fish products. Crit. Rev. Food Sci. Nutr.,  2013, 53(2), 162-179.
[http://dx.doi.org/10.1080/10408398.2010.518775] [PMID: 23072531] 
[120] 
Fisher, S.L. Glutamate racemase as a target for drug discovery. Microb. Biotechnol.,  2008, 1(5), 345-360.
[http://dx.doi.org/10.1111/j.1751-7915.2008.00031.x] [PMID: 21261855] 
[121] 
Weidenmaier, C.; Peschel, A. Teichoic acids and related cell-wall glycopolymers in Gram-positive physiology and host interactions. Nat. Rev. Microbiol.,  2008, 6(4), 276-287.
[http://dx.doi.org/10.1038/nrmicro1861] [PMID: 18327271] 
[122] 
Beeby, M.; Gumbart, J.C.; Roux, B.; Jensen, G.J. Architecture and assembly of the Gram-positive cell wall. Mol. Microbiol.,  2013, 88(4), 664-672.
[http://dx.doi.org/10.1111/mmi.12203] [PMID: 23600697] 
[123] 
Yuan, B.; Cheng, A.; Wang, M. Polysaccharide export outer membrane proteins in Gram-negative bacteria. Future Microbiol.,  2013, 8(4), 525-535.
[http://dx.doi.org/10.2217/fmb.13.13] [PMID: 23534363] 
[124] 
Typas, A.; Banzhaf, M.; Gross, C.A.; Vollmer, W. From the regulation of peptidoglycan synthesis to bacterial growth and morphology. Nat. Rev. Microbiol.,  2011, 10(2), 123-136.
[http://dx.doi.org/10.1038/nrmicro2677] [PMID: 22203377] 
[125] 
Pojer, E.; Mattivi, F.; Johnson, D.; Stockley, C.S. The Case for Anthocyanin Consumption to Promote Human Health: A Review. Compr. Rev. Food Sci. Food Saf.,  2013, 12(5), 483-508.
[http://dx.doi.org/10.1111/1541-4337.12024] 
[126] 
Din, W.M.; Jin, K.T.; Ramli, R.; Khaithir, T.M.; Wiart, C. Antibacterial effects of ellagitannins from Acalypha wilkesiana var. macafeana hort.: surface morphology analysis with environmental scanning electron microscopy and synergy with antibiotics. Phytother. Res.,  2013, 27(9), 1313-1320.
[http://dx.doi.org/10.1002/ptr.4876] [PMID: 23109276] 
[127] 
Lambert, R.J.; Skandamis, P.N.; Coote, P.J.; Nychas, G.J. A study of the minimum inhibitory concentration and mode of action of oregano essential oil, thymol and carvacrol. J. Appl. Microbiol.,  2001, 91(3), 453-462.
[http://dx.doi.org/10.1046/j.1365-2672.2001.01428.x] [PMID: 11556910] 
[128] 
Wang, L.H.; Wang, M.S.; Zeng, X.A.; Xu, X.M.; Brennan, C.S. Membrane and genomic DNA dual-targeting of citrus flavonoid naringenin against Staphylococcus aureus. Integr. Biol.,  2017, 9(10), 820-829.
[http://dx.doi.org/10.1039/C7IB00095B] [PMID: 28862705] 
[129] 
Caturla, N.; Vera-Samper, E.; Villalaín, J.; Mateo, C.R.; Micol, V. The relationship between the antioxidant and the antibacterial properties of galloylated catechins and the structure of phospholipid model membranes. Free Radic. Biol. Med.,  2003, 34(6), 648-662.
[http://dx.doi.org/10.1016/S0891-5849(02)01366-7] [PMID: 12633742] 
[130] 
Nakayama, M.; Shimatani, K.; Ozawa, T.; Shigemune, N.; Tomiyama, D.; Yui, K.; Katsuki, M.; Ikeda, K.; Nonaka, A.; Miyamoto, T. Mechanism for the antibacterial action of epigallocatechin gallate (EGCg) on Bacillus subtilis. Biosci. Biotechnol. Biochem.,  2015, 79(5), 845-854.
[http://dx.doi.org/10.1080/09168451.2014.993356] [PMID: 25559894] 
[131] 
Sirk, T.W.F.; Brown, E.F.; Sum, A.K.; Friedman, M. Molecular dynamics study on the biophysical interactions of seven green tea catechins with lipid bilayers of cell membranes. J. Agric. Food Chem.,  2008, 56(17), 7750-7758.
[http://dx.doi.org/10.1021/jf8013298] [PMID: 18672886] 
[132] 
Bernal, P.; Lemaire, S.; Pinho, M.G.; Mobashery, S.; Hinds, J.; Taylor, P.W. Insertion of epicatechin gallate into the cytoplasmic membrane of methicillin-resistant Staphylococcus aureus disrupts penicillin-binding protein (PBP) 2a-mediated beta-lactam resistance by delocalizing PBP2. J. Biol. Chem.,  2010, 285(31), 24055-24065.
[http://dx.doi.org/10.1074/jbc.M110.114793] [PMID: 20516078] 
[133] 
Mandal, S.M.; Dias, R.O.; Franco, O.L. Phenolic Compounds in Antimicrobial Therapy. J. Med. Food,  2017, 20(10), 1031-1038.
[http://dx.doi.org/10.1089/jmf.2017.0017] [PMID: 28661772] 
[134] 
Lin, R.D.; Chin, Y.P.; Hou, W.C.; Lee, M.H. The effects of antibiotics combined with natural polyphenols against clinical methicillin-resistant Staphylococcus aureus (MRSA). Planta Med.,  2008, 74(8), 840-846.
[http://dx.doi.org/10.1055/s-2008-1074559] [PMID: 18546080] 
[135] 
Kusuda, M.; Inada, K.; Ogawa, T.O.; Yoshida, T.; Shiota, S.; Tsuchiya, T.; Hatano, T. Polyphenolic constituent structures of Zanthoxylum piperitum fruit and the antibacterial effects of its polymeric procyanidin on methicillin-resistant Staphylococcus aureus. Biosci. Biotechnol. Biochem.,  2006, 70(6), 1423-1431.
[http://dx.doi.org/10.1271/bbb.50669] [PMID: 16794323] 
[136] 
Nozaki, A.; Hori, M.; Kimura, T.; Ito, H.; Hatano, T. Interaction of polyphenols with proteins: binding of (-)-epigallocatechin gallate to serum albumin, estimated by induced circular dichroism. Chem. Pharm. Bull. (Tokyo),  2009, 57(2), 224-228.
[http://dx.doi.org/10.1248/cpb.57.224] [PMID: 19182419] 
[137] 
Rothwell, J.A.; Perez-Jimenez, J.; Neveu, V.; Medina-Remon, A.; M'Hiri, N.; Garcia-Lobato, P.; Manach, C.; Knox, C.; Eisner, R.; Wishart, D.S.; Scalbert, A. Phenol-
Explorer 3.0: a major update of the Phenol-Explorer database
to incorporate data on the effects of food processing on
polyphenol content Database (Oxford),,  2013, 2013
[138] 
Encinar, J.A.; Fernández-Ballester, G.; Galiano-Ibarra, V.; Micol, V. In silico approach for the discovery of new PPARγ modulators among plant-derived polyphenols. Drug Des. Devel. Ther.,  2015, 9, 5877-5895.
[http://dx.doi.org/10.2147/DDDT.S93449] [PMID: 26604687] 
[139] 
Galiano, V.; Garcia-Valtanen, P.; Micol, V.; Encinar, J.A. Looking for inhibitors of the dengue virus NS5 RNA-dependent RNA-polymerase using a molecular docking approach. Drug Des. Devel. Ther.,  2016, 10, 3163-3181.
[http://dx.doi.org/10.2147/DDDT.S117369] [PMID: 27784988] 
[140] 
Trott, O.; Olson, A.J. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem.,  2010, 31(2), 455-461.
[PMID: 19499576] 
[141] 
Biasini, M.; Bienert, S.; Waterhouse, A.; Arnold, K.; Studer, G.; Schmidt, T.; Kiefer, F.; Gallo Cassarino, T.; Bertoni, M.; Bordoli, L.; Schwede, T. SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Res.,  2014, 42(W1), W252-8
[http://dx.doi.org/10.1093/nar/gku340] [PMID: 24782522] 
[142] 
Cho, Y.S.; Schiller, N.L.; Oh, K.H. Antibacterial effects of green tea polyphenols on clinical isolates of methicillin-resistant Staphylococcus aureus. Curr. Microbiol.,  2008, 57(6), 542-546.
[http://dx.doi.org/10.1007/s00284-008-9239-0] [PMID: 18781360] 
[143] 
Radji, M.; Agustama, R.A.; Elya, B.; Tjampakasari, C.R. Antimicrobial activity of green tea extract against isolates of methicillin-resistant Staphylococcus aureus and multi-drug resistant Pseudomonas aeruginosa. Asian Pac. J. Trop. Biomed.,  2013, 3(8), 663-667.
[http://dx.doi.org/10.1016/S2221-1691(13)60133-1] [PMID: 23905026] 
[144] 
Ankolekar, C.; Johnson, D. Pinto, Mda.S.; Johnson, K.; Labbe, R.; Shetty, K. Inhibitory potential of tea polyphenolics and influence of extraction time against Helicobacter pylori and lack of inhibition of beneficial lactic acid bacteria. J. Med. Food,  2011, 14(11), 1321-1329.
[http://dx.doi.org/10.1089/jmf.2010.0237] [PMID: 21663484] 
[145] 
Lee, P.; Tan, K.S. Effects of Epigallocatechin gallate against Enterococcus faecalis biofilm and virulence. Arch. Oral Biol.,  2015, 60(3), 393-399.
[http://dx.doi.org/10.1016/j.archoralbio.2014.11.014] [PMID: 25526623] 
[146] 
Ashiuchi, M.; Kuwana, E.; Yamamoto, T.; Komatsu, K.; Soda, K.; Misono, H. Glutamate racemase is an endogenous DNA gyrase inhibitor. J. Biol. Chem.,  2002, 277(42), 39070-39073.
[http://dx.doi.org/10.1074/jbc.C200253200] [PMID: 12213801] 
[147] 
Ashiuchi, M.; Yoshimura, T.; Esaki, N.; Ueno, H.; Soda, K. Inactivation of Glutamate Racemase of Pediococcus pentosaceus with L-Serine O-Sulfate. Biosci. Biotechnol. Biochem.,  1993, 57(11), 1978-1979.
[http://dx.doi.org/10.1271/bbb.57.1978] 
[148] 
de Dios, A.; Prieto, L.; Martín, J.A.; Rubio, A.; Ezquerra, J.; Tebbe, M.; López de Uralde, B.; Martín, J.; Sánchez, A.; LeTourneau, D.L.; McGee, J.E.; Boylan, C.; Parr, T.R., Jr; Smith, M.C. 4-Substituted D-glutamic acid analogues: the first potent inhibitors of glutamate racemase (MurI) enzyme with antibacterial activity. J. Med. Chem.,  2002, 45(20), 4559-4570.
[http://dx.doi.org/10.1021/jm020901d] [PMID: 12238935] 
[149] 
Lundqvist, T.; Fisher, S.L.; Kern, G.; Folmer, R.H.; Xue, Y.; Newton, D.T.; Keating, T.A.; Alm, R.A.; de Jonge, B.L. Exploitation of structural and regulatory diversity in glutamate racemases. Nature,  2007, 447(7146), 817-822.
[http://dx.doi.org/10.1038/nature05689] [PMID: 17568739] 
[150] 
Geng, B.; Basarab, G.; Comita-Prevoir, J.; Gowravaram, M.; Hill, P.; Kiely, A.; Loch, J.; MacPherson, L.; Morningstar, M.; Mullen, G.; Osimboni, E.; Satz, A.; Eyermann, C.; Lundqvist, T. Potent and selective inhibitors of Helicobacter pylori glutamate racemase (MurI): pyridodiazepine amines. Bioorg. Med. Chem. Lett.,  2009, 19(3), 930-936.
[http://dx.doi.org/10.1016/j.bmcl.2008.11.113] [PMID: 19097892] 
[151] 
Breault, G.A.; Comita-Prevoir, J.; Eyermann, C.J.; Geng, B.; Petrichko, R.; Doig, P.; Gorseth, E.; Noonan, B. Exploring 8-benzyl pteridine-6,7-diones as inhibitors of glutamate racemase (MurI) in gram-positive bacteria. Bioorg. Med. Chem. Lett.,  2008, 18(23), 6100-6103.
[http://dx.doi.org/10.1016/j.bmcl.2008.10.022] [PMID: 18947997] 
[152] 
Sujana, P.; Sridhar, T.M.; Josthna, P.; Naidu, C.V. Antibacterial Activity and Phytochemical Analysis of Mentha piperita; L. (Peppermint)—An Important Multipurpose Medicinal Plant. Am. J. Plant Sci.,  2013, 4(1), 77-83.
[http://dx.doi.org/10.4236/ajps.2013.41012] 
[153] 
Reed, P.; Atilano, M.L.; Alves, R.; Hoiczyk, E.; Sher, X.; Reichmann, N.T.; Pereira, P.M.; Roemer, T.; Filipe, S.R.; Pereira-Leal, J.B.; Ligoxygakis, P.; Pinho, M.G. Staphylococcus aureus Survives with a Minimal Peptidoglycan Synthesis Machine but Sacrifices Virulence and Antibiotic Resistance. PLoS Pathog.,  2015, 11(5), e1004891
[http://dx.doi.org/10.1371/journal.ppat.1004891] [PMID: 25951442] 
[154] 
Zulkifli, A.; Ahmad, A. Detection of methicillin resistant
 Staphylococcus aureus (MRSA) from recreational beach using
 the mecA gene.AIP Conf. Proc; , 2015. , 1678030011
[http://dx.doi.org/10.1063/1.4931232] 
[155] 
Favela-Hernández, J.; Clemente-Soto, A.; Balderas-Rentería, I.; Garza-González, E.; Camacho-Corona, M. Potential Mechanism of Action of 3′-Demethoxy-6-O-demethyl-isoguaiacin on Methicillin Resistant Staphylococcus aureus. Molecules,  2015, 20(7), 12450-12458.
[http://dx.doi.org/10.3390/molecules200712450] 
[156] 
Monnet, V. Bacterial oligopeptide-binding proteins. Cell. Mol. Life Sci.,  2003, 60(10), 2100-2114.
[http://dx.doi.org/10.1007/s00018-003-3054-3] [PMID: 14618258] 
[157] 
Adhikari, S.; Curtis, P.D. DNA methyltransferases and epigenetic regulation in bacteria. FEMS Microbiol. Rev.,  2016, 40(5), 575-591.
[http://dx.doi.org/10.1093/femsre/fuw023] [PMID: 27476077] 
[158] 
Palacios, L.; Rosado, H.; Micol, V.; Rosato, A.E.; Bernal, P.; Arroyo, R.; Grounds, H.; Anderson, J.C.; Stabler, R.A.; Taylor, P.W. Staphylococcal phenotypes induced by naturally occurring and synthetic membrane-interactive polyphenolic β-lactam resistance modifiers. PLoS One,  2014, 9(4), e93830
[http://dx.doi.org/10.1371/journal.pone.0093830] [PMID: 24699700] 
[159] 
Murtaza, G.; Karim, S.; Akram, M.R.; Khan, S.A.; Azhar, S.; Mumtaz, A.; Bin Asad, M.H. Caffeic acid phenethyl ester and therapeutic potentials. BioMed Res. Int.,  2014, 2014, 145342
[http://dx.doi.org/10.1155/2014/145342] [PMID: 24971312] 
[160] 
Mori, A.T.S. Antibacterial activity and mode of action of plant flavonoids against Proteus vulgaris and Staphylococcus aureus. Phytochemistry,  1987, 26(8), 2231-2234.
[http://dx.doi.org/10.1016/S0031-9422(00)84689-0] 
[161] 
Xu, H.X.; Lee, S.F. Activity of plant flavonoids against antibiotic-resistant bacteria. Phytother. Res.,  2001, 15(1), 39-43.
[http://dx.doi.org/10.1002/1099-1573(200102)15:1<39:AID-PTR684>3.0.CO;2-R] [PMID: 11180521] 
[162] 
Ghimire, B.K.; Yu, C.Y.; Chung, I.M. Assessment of the phenolic profile, antimicrobial activity and oxidative stability of transgenic Perilla frutescens L.overexpressing tocopherol methyltransferase (γ-tmt) gene. Plant Physiol. Biochem.,  2017, 118, 77-87.
[http://dx.doi.org/10.1016/j.plaphy.2017.06.006] [PMID: 28622602] 
[163] 
Dias-Souza, M.V.; Dos Santos, R.M.; Cerávolo, I.P.; Cosenza, G.; Ferreira Marçal, P.H.; Figueiredo, F.J.B. Euterpe oleracea pulp extract: Chemical analyses, antibiofilm activity against Staphylococcus aureus, cytotoxicity and interference on the activity of antimicrobial drugs. Microb. Pathog.,  2018, 114, 29-35.
[http://dx.doi.org/10.1016/j.micpath.2017.11.006] [PMID: 29146496] 
[164] 
Dias-Souza, M.V.; Dos Santos, R.M.; de Siqueira, E.P.; Ferreira-Marçal, P.H. Antibiofilm activity of cashew juice pulp against Staphylococcus aureus, high performance liquid chromatography/diode array detection and gas chromatography-mass spectrometry analyses, and interference on antimicrobial drugs. Yao Wu Shi Pin Fen Xi,  2017, 25(3), 589-596.
[http://dx.doi.org/10.1016/j.jfda.2016.07.009] [PMID: 28911645] 
[165] 
Kline, K.A.; Lewis, A.L. Gram-Positive Uropathogens, Polymicrobial Urinary Tract Infection, and the Emerging Microbiota of the Urinary Tract. Microbiol. Spectr.,  2016, 4(2)
[http://dx.doi.org/10.1128/microbiolspec.UTI-0012-2012] [PMID: 27227294] 
[166] 
Macé, S.; Truelstrup Hansen, L.; Rupasinghe, H.P.V. Anti-Bacterial Activity of Phenolic Compounds against Streptococcus pyogenes. Medicines (Basel),  2017, 4(2), E25
[http://dx.doi.org/10.3390/medicines4020025] [PMID: 28930240] 
[167] 
Singh, A.K.; Prakash, P.; Singh, R.; Nandy, N.; Firdaus, Z.; Bansal, M.; Singh, R.K.; Srivastava, A.; Roy, J.K.; Mishra, B.; Singh, R.K. Curcumin Quantum Dots Mediated Degradation of Bacterial Biofilms. Front. Microbiol.,  2017, 8, 1517.
[http://dx.doi.org/10.3389/fmicb.2017.01517] [PMID: 28848526] 
[168] 
Lin, Y.T.; Kwon, Y.I.; Labbe, R.G.; Shetty, K. Inhibition of Helicobacter pylori and associated urease by oregano and cranberry phytochemical synergies. Appl. Environ. Microbiol.,  2005, 71(12), 8558-8564.
[http://dx.doi.org/10.1128/AEM.71.12.8558-8564.2005] [PMID: 16332847] 
[169] 
Shetty, K.; Wahlqvist, M.L. A model for the role of the proline-linked pentose-phosphate pathway in phenolic phytochemical bio-synthesis and mechanism of action for human health and environmental applications. Asia Pac. J. Clin. Nutr.,  2004, 13(1), 1-24.
[PMID: 15003910] 
[170] 
Ooshima, T.; Minami, T.; Aono, W.; Izumitani, A.; Sobue, S.; Fujiwara, T.; Kawabata, S.; Hamada, S. Oolong tea polyphenols inhibit experimental dental caries in SPF rats infected with mutans streptococci. Caries Res.,  1993, 27(2), 124-129.
[http://dx.doi.org/10.1159/000261529] [PMID: 8319255] 
[171] 
Gregoire, S.; Singh, A.P.; Vorsa, N.; Koo, H. Influence of cranberry phenolics on glucan synthesis by glucosyltransferases and Streptococcus mutans acidogenicity. J. Appl. Microbiol.,  2007, 103(5), 1960-1968.
[http://dx.doi.org/10.1111/j.1365-2672.2007.03441.x] [PMID: 17953606] 
[172] 
Yoo, S.; Murata, R.M.; Duarte, S. Antimicrobial traits of tea- and cranberry-derived polyphenols against Streptococcus mutans. Caries Res.,  2011, 45(4), 327-335.
[http://dx.doi.org/10.1159/000329181] [PMID: 21720161] 
[173] 
Hisano, M.; Yamaguchi, K.; Inoue, Y.; Ikeda, Y.; Iijima, M.; Adachi, M.; Shimamura, T. Inhibitory effect of catechin against the superantigen staphylococcal enterotoxin B (SEB). Arch. Dermatol. Res.,  2003, 295(5), 183-189.
[http://dx.doi.org/10.1007/s00403-003-0411-x] [PMID: 12883826] 
[174] 
Tsuchiya, H.; Iinuma, M. Reduction of membrane fluidity by antibacterial sophoraflavanone G isolated from Sophora exigua. Phytomedicine,  2000, 7(2), 161-165.
[http://dx.doi.org/10.1016/S0944-7113(00)80089-6] [PMID: 10839220] 
[175] 
Mirzoeva, O.K.; Grishanin, R.N.; Calder, P.C. Antimicrobial action of propolis and some of its components: the effects on growth, membrane potential and motility of bacteria. Microbiol. Res.,  1997, 152(3), 239-246.
[http://dx.doi.org/10.1016/S0944-5013(97)80034-1] [PMID: 9352659] 
[176] 
Monagas, M.; Urpi-Sarda, M.; Sánchez-Patán, F.; Llorach, R.; Garrido, I.; Gómez-Cordovés, C.; Andres-Lacueva, C.; Bartolomé, B. Insights into the metabolism and microbial biotransformation of dietary flavan-3-ols and the bioactivity of their metabolites. Food Funct.,  2010, 1(3), 233-253.
[http://dx.doi.org/10.1039/c0fo00132e] [PMID: 21776473] 
[177] 
Ait-Ouazzou, A.; Espina, L.; Gelaw, T.K.; de Lamo-Castellví, S.; Pagán, R.; García-Gonzalo, D. New insights in mechanisms of bacterial inactivation by carvacrol. J. Appl. Microbiol.,  2013, 114(1), 173-185.
[http://dx.doi.org/10.1111/jam.12028] [PMID: 23035895] 
[178] 
Gupta, P.D.; Birdi, T.J. Development of botanicals to combat antibiotic resistance. J. Ayurveda Integr. Med.,  2017, 8(4), 266-275.
[http://dx.doi.org/10.1016/j.jaim.2017.05.004] [PMID: 28869082] 
[179] 
Warnke, P.H.; Becker, S.T.; Podschun, R.; Sivananthan, S.; Springer, I.N.; Russo, P.A.; Wiltfang, J.; Fickenscher, H.; Sherry, E. The battle against multi-resistant strains: Renaissance of antimicrobial essential oils as a promising force to fight hospital-acquired infections. J. Craniomaxillofac. Surg.,  2009, 37(7), 392-397.
[http://dx.doi.org/10.1016/j.jcms.2009.03.017] [PMID: 19473851] 
[180] 
Brooker, J.M.P. Streptococcus caprinus sp.nov., a tannin-resistant ruminal bacterium from feral goats. Appl. Microbiol.,  1994, 18, 313-318.
[http://dx.doi.org/10.1111/j.1472-765X.1994.tb00877.x] 
[181] 
Smith, A.H.; Zoetendal, E.; Mackie, R.I. Bacterial mechanisms to overcome inhibitory effects of dietary tannins. Microb. Ecol.,  2005, 50(2), 197-205.
[http://dx.doi.org/10.1007/s00248-004-0180-x] [PMID: 16222487] 
[182] 
Marcal, F.J.; Cortez, D.A.; Ueda-Nakamura, T.; Nakamura, C.V.; Dias Filho, B.P. Activity of the extracts and neolignans from Piper regnellii against methicillin-resistant Staphylococcus aureus (MRSA). Molecules,  2010, 15, 2060-2069.
[http://dx.doi.org/10.3390/molecules15042060] [PMID: 20428025] 
Cite As
Current Medicinal Chemistry

Antimicrobial Capacity of Plant Polyphenols against Gram-positive Bacteria: A Comprehensive Review

Abstract
