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Nontraditional therapies to treat Helicobacter pylori infection

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Abstract

The Gram-negative pathogen Helicobacter pylori is increasingly more resistant to the three major antibiotics (metronidazole, clarithromycin and amoxicillin) that are most commonly used to treat infection. As a result, there is an increased rate of treatment failure; this translates into an overall higher cost of treatment due to the need for increased length of treatment and/or the requirement for combination or sequential therapy. Given the rise in antibiotic resistance, the complicated treatment regime, and issues related to patient compliance that stem from the duration and complexity of treatment, there is clearly a pressing need for the development of novel therapeutic strategies to combat H. pylori infection. As such, researchers are actively investigating the utility of antimicrobial peptides, small molecule inhibitors and naturopathic therapies. Herein we review and discuss each of these novel approaches as a means to target this important gastric pathogen.

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References

  • al Somal, N., Coley, K.E., Molan, P.C., and Hancock, B.M. 1994. Susceptibility of Helicobacter pylori to the antibacterial activity of manuka honey. J. R. Soc. Med. 87, 9–12.

    PubMed  PubMed Central  Google Scholar 

  • Amundsen, S.K., Fero, J., Hansen, L.M., Cromie, G.A., Solnick, J.V., Smith, G.R., and Salama, N.R. 2008. Helicobacter pylori AddAB helicase-nuclease and RecA promote recombination-related DNA repair and survival during stomach colonization. Mol. Microbiol. 69, 994–1007.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Andra, J., Goldmann, T., Ernst, C.M., Peschel, A., and Gutsmann, T. 2011. Multiple peptide resistance factor (MprF)-mediated resistance of Staphylococcus aureus against antimicrobial peptides coincides with a modulated peptide interaction with artificial membranes comprising lysyl-phosphatidylglycerol. J. Biol. Chem. 286, 18692–18700.

    PubMed  PubMed Central  Google Scholar 

  • Andreu, D. and Rivas, L. 1998. Animal antimicrobial peptides: an overview. Biopolymers 47, 415–433.

    PubMed  CAS  Google Scholar 

  • Bae, E.A., Han, M.J., Baek, N.I., and Kim, D.H. 2001. In vitro anti-Helicobacter pylori activity of panaxytriol isolated from ginseng. Arch. Pharm. Res. 24, 297–299.

    PubMed  CAS  Google Scholar 

  • Basile, A., Senatore, F., Gargano, R., Sorbo, S., Del Pezzo, M., Lavitola, A., Ritieni, A., Bruno, M., Spatuzzi, D., Rigano, D., and et al. 2006. Antibacterial and antioxidant activities in Sideritis italica (Miller) Greuter et Burdet essential oils. J. Ethnopharmacol. 107, 240–248.

    PubMed  CAS  Google Scholar 

  • Bayer, A.S., Prasad, R., Chandra, J., Koul, A., Smriti, M., Varma, A., Skurray, R.A., Firth, N., Brown, M.H., Koo, S.P., and et al. 2000. In vitro resistance of Staphylococcus aureus to thrombin-induced platelet microbicidal protein is associated with alterations in cytoplasmic membrane fluidity. Infect. Immun. 68, 3548–3553.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Bazzoli, F., Pozzato, P., and Rokkas, T. 2002. Helicobacter pylori: the challenge in therapy. Helicobacter 7Suppl 1, 43–49.

    PubMed  CAS  Google Scholar 

  • Bergonzelli, G.E., Donnicola, D., Porta, N., and Corthesy-Theulaz, I.E. 2003. Essential oils as components of a diet-based approach to management of Helicobacter infection. Antimicrob. Agents Chemother. 47, 3240–3246.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Bertoli Neto, J.L., Lourenco, L.G., Bertoli, C.F., Ulbrich, F.S., Sabbi, A.R., and Bueno, A.G. 2006. Evaluation of the efficacy of triple therapy regimen for Helicobacter pylori eradication in gastrectomized patients with gastric adenocarcinoma. Gastric Cancer 9, 291–294.

    PubMed  Google Scholar 

  • Bourke, B., Jones, N., and Sherman, P. 1996. Helicobacter pylori infection and peptic ulcer disease in children. Pediatr. Infect. Dis. J. 15, 1–13.

    PubMed  CAS  Google Scholar 

  • Breukink, E., Wiedemann, I., van Kraaij, C., Kuipers, O.P., Sahl, H.G., and de Kruijff, B. 1999. Use of the cell wall precursor lipid II by a pore-forming peptide antibiotic. Science 286, 2361–2364.

    PubMed  CAS  Google Scholar 

  • Brogden, K.A. 2005. Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat. Rev. Microbiol. 3, 238–250.

    PubMed  CAS  Google Scholar 

  • Calvet, X., Ramirez Lazaro, M.J., Lehours, P., and Megraud, F. 2013. Diagnosis and epidemiology of Helicobacter pylori infection. Helicobacter 18 Suppl 1, 5–11.

    PubMed  Google Scholar 

  • Canizares, P., Gracia, I., Gomez, L.A., Martin de Argila, C., Boixeda, D., Garcia, A., and de Rafael, L. 2004. Allyl-thiosulfinates, the bacteriostatic compounds of garlic against Helicobacter pylori. Biotechnol. Prog. 20, 397–401.

    PubMed  CAS  Google Scholar 

  • Canizares, P., Gracia, I., Gomez, L.A., Martin de Argila, C., de Rafael, L., and Garcia, A. 2002. Optimization of Allium sativum solvent extraction for the inhibition of in vitro growth of Helicobacter pylori. Biotechnol. Prog. 18, 1227–1232.

    PubMed  CAS  Google Scholar 

  • Chen, L., Sung, S.S., Yip, M.L., Lawrence, H.R., Ren, Y., Guida, W.C., Sebti, S.M., Lawrence, N.J., and Wu, J. 2006. Discovery of a novel shp2 protein tyrosine phosphatase inhibitor. Mol. Pharmacol. 70, 562–570.

    PubMed  CAS  Google Scholar 

  • Cremades, N., Bueno, M., Toja, M., and Sancho, J. 2005. Towards a new therapeutic target: Helicobacter pylori flavodoxin. Biophys. Chem. 115, 267–276.

    PubMed  CAS  Google Scholar 

  • Cwikla, C., Schmidt, K., Matthias, A., Bone, K.M., Lehmann, R., and Tiralongo, E. 2010. Investigations into the antibacterial activities of phytotherapeutics against Helicobacter pylori and Campylobacter jejuni. Phytother. Res. 24, 649–656.

    PubMed  CAS  Google Scholar 

  • de Jonge, B.L., Kutschke, A., Uria-Nickelsen, M., Kamp, H.D., and Mills, S.D. 2009. Pyrazolopyrimidinediones are selective agents for Helicobacter pylori that suppress growth through inhibition of glutamate racemase (MurI). Antimicrob. Agents Chemother. 53, 3331–3336.

    PubMed  PubMed Central  Google Scholar 

  • De Leo, M., De Tommasi, N., Sanogo, R., D’Angelo, V., Germano, M.P., Bisignano, G., and Braca, A. 2006. Triterpenoid saponins from Pteleopsis suberosa stem bark. Phytochemistry 67, 2623–2629.

    PubMed  Google Scholar 

  • De, R., Kundu, P., Swarnakar, S., Ramamurthy, T., Chowdhury, A., Nair, G.B., and Mukhopadhyay, A.K. 2009. Antimicrobial activity of curcumin against Indian Helicobacter pylori and also during mice infection. Antimicrob. Agents Chemother. 53, 1592–1597.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Delcour, A.H. 2009. Outer membrane permeability and antibiotic resistance. Biochim. Biophys. Acta. 1794, 808–816.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Dunn, B.E., Campbell, G.P., Perez-Perez, G.I., and Blaser, M.J. 1990. Purification and characterization of urease from Helicobacter pylori. J. Biol. Chem. 265, 9464–9469.

    PubMed  CAS  Google Scholar 

  • Dunn, B.E., Cohen, H., and Blaser, M.J. 1997. Helicobacter pylori. Clin. Microbiol. Rev. 10, 720–741.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Eftekhar, F., Nariman, F., Yousefzadi, M., Hadiand, J., and Ebrahimi, S.N. 2009. Anti-Helicobacter pylori activity and essential oil composition of Thymus caramanicus from Iran. Nat. Prod. Commun. 4, 1139–1142.

    PubMed  CAS  Google Scholar 

  • Eisenberg, D.M., Davis, R.B., Ettner, S.L., Appel, S., Wilkey, S., Van Rompay, M., and Kessler, R.C. 1998. Trends in alternative medicine use in the United States, 1990–1997: results of a follow-up national survey. JAMA 280, 1569–1575.

    PubMed  CAS  Google Scholar 

  • Epand, R.F., Sarig, H., Mor, A., and Epand, R.M. 2009. Cell-wall interactions and the selective bacteriostatic activity of a miniature oligo-acyl-lysyl. Biophys. J. 97, 2250–2257.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Escobedo-Hinojosa, W.I., Del Carpio, J.D., Palacios-Espinosa, J.F., and Romero, I. 2012. Contribution to the ethnopharmacological and anti-Helicobacter pylori knowledge of Cyrtocarpa procera Kunth (Anacardiaceae). J. Ethnopharmacol. 143, 363–371.

    PubMed  Google Scholar 

  • Everhart, J.E. 2000. Recent developments in the epidemiology of Helicobacter pylori. Gastroenterol. Clin. North Am. 29, 559–578.

    PubMed  CAS  Google Scholar 

  • Fahey, J.W., Haristoy, X., Dolan, P.M., Kensler, T.W., Scholtus, I., Stephenson, K.K., Talalay, P., and Lozniewski, A. 2002. Sulforaphane inhibits extracellular, intracellular, and antibiotic-resistant strains of Helicobacter pylori and prevents benzo[a]pyrene-induced stomach tumors. Proc. Natl. Acad. Sci. USA 99, 7610–7615.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Fani, A., Fani, I., Delavar, M., Fani, P., Eshrati, B., and Elahi, M. 2007. Combined garlic-omeprazole versus standard quadruple therapy for eradication of Helicobacter pylori infection. Indian J. Gastroenterol. 26, 145–146.

    PubMed  CAS  Google Scholar 

  • Fisher, P. and Ward, A. 1994. Complementary medicine in Europe. BMJ 309, 107–111.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Gail, M.H., Pfeiffer, R.M., Brown, L.M., Zhang, L., Ma, J.L., Pan, K.F., Liu, W.D., and You, W.C. 2007. Garlic, vitamin, and antibiotic treatment for Helicobacter pylori: a randomized factorial controlled trial. Helicobacter 12, 575–578.

    PubMed  Google Scholar 

  • Geng, B., Basarab, G., Comita-Prevoir, J., Gowravaram, M., Hill, P., Kiely, A., Loch, J., MacPherson, L., Morningstar, M., Mullen, G., and et al. 2009. Potent and selective inhibitors of Helicobacter pylori glutamate racemase (MurI): pyridodiazepine amines. Bioorg. Med. Chem. Lett. 19, 930–936.

    PubMed  CAS  Google Scholar 

  • Glassman, M.S., Dallal, S., Berezin, S.H., Bostwick, H.E., Newman, L.J., Perez-Perez, G.I., and Blaser, M.J. 1990. Helicobacter pylori-related gastroduodenal disease in children. Diagnostic utility of enzyme-linked immunosorbent assay. Dig. Dis. Sci. 35, 993–997.

    PubMed  CAS  Google Scholar 

  • Graham, D.Y. and Fischbach, L. 2010. Helicobacter pylori treatment in the era of increasing antibiotic resistance. Gut 59, 1143–1153.

    PubMed  CAS  Google Scholar 

  • Guina, T., Yi, E.C., Wang, H., Hackett, M., and Miller, S.I. 2000. A PhoP-regulated outer membrane protease of Salmonella enterica serovar typhimurium promotes resistance to alpha-helical antimicrobial peptides. J. Bacteriol. 182, 4077–4086.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Guo, L., Lim, K.B., Poduje, C.M., Daniel, M., Gunn, J.S., Hackett, M., and Miller, S.I. 1998. Lipid A acylation and bacterial resistance against vertebrate antimicrobial peptides. Cell 95, 189–198.

    PubMed  CAS  Google Scholar 

  • Ha, N.C., Oh, S.T., Sung, J.Y., Cha, K.A., Lee, M.H., and Oh, B.H. 2001. Supramolecular assembly and acid resistance of Helicobacter pylori urease. Nat. Struct. Biol. 8, 505–509.

    PubMed  CAS  Google Scholar 

  • Hamanaka, Y., Nakashima, M., Wada, A., Ito, M., Kurazono, H., Hojo, H., Nakahara, Y., Kohno, S., Hirayama, T., and Sekine, I. 2001. Expression of human beta-defensin 2 (hBD-2) in Helicobacter pylori induced gastritis: antibacterial effect of hBD-2 against Helicobacter pylori. Gut 49, 481–487.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Haniadka, R., Saldanha, E., Sunita, V., Palatty, P.L., Fayad, R., and Baliga, M.S. 2013. A review of the gastroprotective effects of ginger (Zingiber officinale Roscoe). Food Funct. 4, 845–855.

    PubMed  CAS  Google Scholar 

  • Hase, K., Murakami, M., Iimura, M., Cole, S.P., Horibe, Y., Ohtake, T., Obonyo, M., Gallo, R.L., Eckmann, L., and Kagnoff, M.F. 2003. Expression of LL-37 by human gastric epithelial cells as a potential host defense mechanism against Helicobacter pylori. Gastroenterology 125, 1613–1625.

    PubMed  CAS  Google Scholar 

  • Hilleringmann, M., Pansegrau, W., Doyle, M., Kaufman, S., Mac-Kichan, M.L., Gianfaldoni, C., Ruggiero, P., and Covacci, A. 2006. Inhibitors of Helicobacter pylori ATPase Cagalpha block CagA transport and cag virulence. Microbiology 152, 2919–2930.

    PubMed  CAS  Google Scholar 

  • Horwith, G., Einck, L., Protopopova, M., and Nacy, C. 2007. Phase 1 safety and pharmacokinetics of SQ109, a new diamine antituberculosis drug. Meeting Abstract, 45th IDSA Annual Meeting, 2007 Oct 4–7; San Diego, CA, USA. Sequella, Inc., Rockville, MD.

    Google Scholar 

  • Huang, J.Q. and Hunt, R.H. 2003. The evolving epidemiology of Helicobacter pylori infection and gastric cancer. Can. J. Gastroenterol. 17Suppl B, 18B–20B.

    PubMed  Google Scholar 

  • Hungin, A.P., Mulligan, C., Pot, B., Whorwell, P., Agreus, L., Fracasso, P., Lionis, C., Mendive, J., Philippart de Foy, J.M., Rubin, G., and et al. 2013. Systematic review: probiotics in the management of lower gastrointestinal symptoms in clinical practice — an evidence-based international guide. Aliment Pharmacol. Ther. 38, 864–886.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Iimuro, M., Shibata, H., Kawamori, T., Matsumoto, T., Arakawa, T., Sugimura, T., and Wakabayashi, K. 2002. Suppressive effects of garlic extract on Helicobacter pylori-induced gastritis in Mongolian gerbils. Cancer Lett. 187, 61–68.

    PubMed  CAS  Google Scholar 

  • Isaacson, P.G. 1994. Gastric lymphoma and Helicobacter pylori. N. Engl. J. Med. 330, 1310–1311.

    PubMed  CAS  Google Scholar 

  • Jang, S.H., Lim, J.W., and Kim, H. 2009. Beta-carotene inhibits Helicobacter pylori-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 in human gastric epithelial AGS cells. J. Physiol. Pharmacol. 60Suppl 7, 131–137.

    PubMed  Google Scholar 

  • Jenssen, H., Hamill, P., and Hancock, R.E. 2006. Peptide antimicrobial agents. Clin. Microbiol. Rev. 19, 491–511.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Jia, L., Noker, P.E., Coward, L., Gorman, G.S., Protopopova, M., and Tomaszewski, J.E. 2006. Interspecies pharmacokinetics and in vitro metabolism of SQ109. Br. J. Pharmacol. 147, 476–485.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Jia, L., Tomaszewski, J.E., Hanrahan, C., Coward, L., Noker, P., Gorman, G., Nikonenko, B., and Protopopova, M. 2005. Pharmacodynamics and pharmacokinetics of SQ109, a new diamine-based antitubercular drug. Br. J. Pharmacol. 144, 80–87.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Jin, T., Bokarewa, M., Foster, T., Mitchell, J., Higgins, J., and Tarkowski, A. 2004. Staphylococcus aureus resists human defensins by production of staphylokinase, a novel bacterial evasion mechanism. J. Immunol. 172, 1169–1176.

    PubMed  CAS  Google Scholar 

  • Johansson, N.L., Pavia, C.S., and Chiao, J.W. 2008. Growth inhibition of a spectrum of bacterial and fungal pathogens by sulforaphane, an isothiocyanate product found in broccoli and other cruciferous vegetables. Planta Med. 74, 747–750.

    PubMed  CAS  Google Scholar 

  • Jones, J.E., Causey, C.P., Lovelace, L., Knuckley, B., Flick, H., Lebioda, L., and Thompson, P.R. 2010. Characterization and inactivation of an agmatine deiminase from Helicobacter pylori. Bioorg. Chem. 38, 62–73.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Jones, K.R., Cha, J.H., and Merrell, D.S. 2008. Who’s winning the war? Molecular mechanisms of antibiotic resistance in Helicobacter pylori. Curr. Drug Ther. 3, 190–203.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Jonkers, D., van den Broek, E., van Dooren, I., Thijs, C., Dorant, E., Hageman, G., and Stobberingh, E. 1999. Antibacterial effect of garlic and omeprazole on Helicobacter pylori. J. Antimicrob. Chemother. 43, 837–839.

    PubMed  CAS  Google Scholar 

  • Kaboli, S.A., Zojaji, H., Mirsattari, D., Talaie, R., Derakhshan, F., Zali, M.R., and Sheikhvatan, M. 2009. Effect of addition of vitamin C to clarithromycin-amoxicillin-omeprazol triple regimen on Helicobacter pylori eradication. Acta Gastroenterol. Belg. 72, 222–224.

    PubMed  Google Scholar 

  • Kawauchi, K., Yagihashi, A., Tsuji, N., Uehara, N., Furuya, D., Kobayashi, D., and Watanabe, N. 2006. Human beta-defensin-3 induction in H. pylori-infected gastric mucosal tissues. World J. Gastroenterol. 12, 5793–5797.

    PubMed  CAS  Google Scholar 

  • Keenan, J.I., Salm, N., Wallace, A.J., and Hampton, M.B. 2012. Using food to reduce H. pylori-associated inflammation. Phytother. Res. 26, 1620–1625.

    PubMed  CAS  Google Scholar 

  • Kim, D.S., Lee, M.S., Kim, Y.S., Kim, D.H., Bae, J.M., Shin, M.H., and Ahn, Y.O. 2005a. Effect modification by vitamin C on the relation between gastric cancer and Helicobacter pylori. Eur. J. Epidemiol. 20, 67–71.

    PubMed  CAS  Google Scholar 

  • Kim, H.J., Kim, M.K., Chang, W.K., Choi, H.S., Choi, B.Y., and Lee, S.S. 2005b. Effect of nutrient intake and Helicobacter pylori infection on gastric cancer in Korea: a case-control study. Nutr. Cancer 52, 138–146.

    PubMed  CAS  Google Scholar 

  • Koosirirat, C., Linpisarn, S., Changsom, D., Chawansuntati, K., and Wipasa, J. 2010. Investigation of the anti-inflammatory effect of Curcuma longa in Helicobacter pylori-infected patients. Int. Immunopharmacol. 10, 815–818.

    PubMed  CAS  Google Scholar 

  • Kottakis, F., Kouzi-Koliakou, K., Pendas, S., Kountouras, J., and Choli-Papadopoulou, T. 2009. Effects of mastic gum Pistacia lentiscus var. Chia on innate cellular immune effectors. Eur. J. Gastroenterol. Hepatol. 21, 143–149.

    PubMed  CAS  Google Scholar 

  • Kraft, C. and Suerbaum, S. 2005. Mutation and recombination in Helicobacter pylori: mechanisms and role in generating strain diversity. Int. J. Med. Microbiol. 295, 299–305.

    PubMed  CAS  Google Scholar 

  • Lee, S.H. and Baek, D.H. 2012. Antibacterial and neutralizing effect of human beta-defensins on Enterococcus faecalis and Enterococcus faecalis lipoteichoic acid. J. Endod. 38, 351–356.

    PubMed  Google Scholar 

  • Lee, J.S., Kim, H.S., Hahm, K.B., Sohn, M.W., Yoo, M., Johnson, J.A., and Surh, Y.J. 2007a. Inhibitory effects of 7-carboxymethyloxy-3,4,5-trimethoxyflavone (DA-6034) on Helicobacter pylori-nduced NF-kappa B activation and iNOS expression in AGS cells. Ann. NY Acad. Sci. 1095, 527–535.

    PubMed  CAS  Google Scholar 

  • Lee, I.O., Lee, K.H., Pyo, J.H., Kim, J.H., Choi, Y.J., and Lee, Y.C. 2007b. Anti-inflammatory effect of capsaicin in Helicobacter pylori-infected gastric epithelial cells. Helicobacter 12, 510–517.

    PubMed  CAS  Google Scholar 

  • Lee, J.S., Oh, T.Y., Kim, Y.K., Baik, J.H., So, S., Hahm, K.B., and Surh, Y.J. 2005. Protective effects of green tea polyphenol extracts against ethanol-induced gastric mucosal damages in rats: stress-responsive transcription factors and MAP kinases as potential targets. Mutat. Res. 579, 214–224.

    PubMed  CAS  Google Scholar 

  • Lee, J.H., Shim, J.S., Chung, M.S., Lim, S.T., and Kim, K.H. 2009. In vitro anti-adhesive activity of green tea extract against pathogen adhesion. Phytother. Res. 23, 460–466.

    PubMed  CAS  Google Scholar 

  • Lee, S.Y., Shin, Y.W., and Hahm, K.B. 2008. Phytoceuticals: mighty but ignored weapons against Helicobacter pylori infection. J. Dig. Dis. 9, 129–139.

    PubMed  CAS  Google Scholar 

  • Lee, K.M., Yeo, M., Choue, J.S., Jin, J.H., Park, S.J., Cheong, J.Y., Lee, K.J., Kim, J.H., and Hahm, K.B. 2004. Protective mechanism of epigallocatechin-3-gallate against Helicobacter pylori-nduced gastric epithelial cytotoxicity via the blockage of TLR-4 signaling. Helicobacter 9, 632–642.

    PubMed  CAS  Google Scholar 

  • Lemos, L.M., Martins, T.B., Tanajura, G.H., Gazoni, V.F., Bonaldo, J., Strada, C.L., Silva, M.G., Dall’oglio, E.L., de Sousa Junior, P.T., and Martins, D.T. 2012. Evaluation of antiulcer activity of chromanone fraction from Calophyllum brasiliesnse Camb. J. Ethnopharmacol. 141, 432–439.

    PubMed  CAS  Google Scholar 

  • Leszczynska, K., Namiot, A., Fein, D.E., Wen, Q., Namiot, Z., Savage, P.B., Diamond, S., Janmey, P.A., and Bucki, R. 2009. Bactericidal activities of the cationic steroid CSA-13 and the cathelicidin peptide LL-37 against Helicobacter pylori in simulated gastric juice. BMC Microbiol. 9, 187.

    PubMed  PubMed Central  Google Scholar 

  • Lien, H.M., Wang, C.Y., Chang, H.Y., Huang, C.L., Peng, M.T., Sing, Y.T., Chen, C.C., and Lai, C.H. 2013. Bioevaluation of Anisomeles indica extracts and their inhibitory effects on Helicobacter pylori-mediated inflammation. J. Ethnopharmacol. 145, 397–401.

    PubMed  CAS  Google Scholar 

  • Lin, Y.T., Kwon, Y.I., Labbe, R.G., and Shetty, K. 2005. Inhibition of Helicobacter pylori and associated urease by oregano and cranberry phytochemical synergies. Appl. Environ. Microbiol. 71, 8558–8564.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Livermore, D.M. 2009. Has the era of untreatable infections arrived? J. Antimicrob. Chemother. 64Suppl 1, i29–36.

    PubMed  CAS  Google Scholar 

  • Lockey, T.D. and Ourth, D.D. 1996. Formation of pores in Escherichia coli cell membranes by a cecropin isolated from hemolymph of Heliothis virescens larvae. Eur. J. Biochem. 236, 263–271.

    PubMed  CAS  Google Scholar 

  • Lundqvist, T., Fisher, S.L., Kern, G., Folmer, R.H., Xue, Y., Newton, D.T., Keating, T.A., Alm, R.A., and de Jonge, B.L. 2007. Exploitation of structural and regulatory diversity in glutamate racemases. Nature 447, 817–822.

    PubMed  CAS  Google Scholar 

  • MacLennan, A.H., Wilson, D.H., and Taylor, A.W. 1996. Prevalence and cost of alternative medicine in Australia. Lancet 347, 569–573.

    PubMed  CAS  Google Scholar 

  • Mahady, G.B., Pendland, S.L., and Chadwick, L.R. 2003. Resveratrol and red wine extracts inhibit the growth of CagA+ strains of Helicobacter pylori in vitro. Am. J. Gastroenterol. 98, 1440–1441.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Mahady, G.B., Pendland, S.L., Stoia, A., Hamill, F.A., Fabricant, D., Dietz, B.M., and Chadwick, L.R. 2005. In vitro susceptibility of Helicobacter pylori to botanical extracts used traditionally for the treatment of gastrointestinal disorders. Phytother. Res. 19, 988–991.

    PubMed  Google Scholar 

  • Mahady, G.B., Pendland, S.L., Yun, G., and Lu, Z.Z. 2002. Turmeric (Curcuma longa) and curcumin inhibit the growth of Helicobacter pylori, a group 1 carcinogen. Anticancer Res. 22, 4179–4181.

    PubMed  CAS  Google Scholar 

  • Makobongo, M.O., Einck, L., Peek, R.M.Jr., and Merrell, D.S. 2013. In vitro characterization of the anti-bacterial activity of SQ109 against Helicobacter pylori. PLoS One 8, e68917.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Makobongo, M.O., Gancz, H., Carpenter, B.M., McDaniel, D.P., and Merrell, D.S. 2012. The oligo-acyl lysyl antimicrobial peptide C12K-2β12 exhibits a dual mechanism of action and demonstrates strong in vivo efficacy against Helicobacter pylori. Antimicrob. Agents Chemother. 56, 378–390.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Makobongo, M.O., Kovachi, T., Gancz, H., Mor, A., and Merrell, D.S. 2009. In vitro antibacterial activity of acyl-lysyl oligomers against Helicobacter pylori. Antimicrob. Agents Chemother. 53, 4231–4239.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Malfertheiner, P. 1993. Compliance, adverse events and antibiotic resistance in Helicobacter pylori treatment. Scand. J. Gastroenterol. 196, 34–37.

    CAS  Google Scholar 

  • Malfertheiner, P., Megraud, F., O’Morain, C.A., Atherton, J., Axon, A.T., Bazzoli, F., Gensini, G.F., Gisbert, J.P., Graham, D.Y., Rokkas, T., and et al. 2012. Management of Helicobacter pylori infection-the Maastricht IV/Florence Consensus Report. Gut 61, 646–664.

    PubMed  CAS  Google Scholar 

  • Malfertheiner, P., Megraud, F., O’Morain, C., Bazzoli, F., El-Omar, E., Graham, D., Hunt, R., Rokkas, T., Vakil, N., and Kuipers, E.J. 2007. Current concepts in the management of Helicobacter pylori infection: the Maastricht III consensus report. Gut 56, 772–781.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Marshall, B.J., Warren, J.R., McGechie, D.B., Francis, G.J., Utley, P.J., Rogers, P.A., and Glancy, R.J. 1984. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1, 1311–1315.

    PubMed  CAS  Google Scholar 

  • Martin, K.W. and Ernst, E. 2003. Herbal medicines for treatment of bacterial infections: a review of controlled clinical trials. J. Antimicrob. Chemother. 51, 241–246.

    PubMed  CAS  Google Scholar 

  • Matsubara, S., Shibata, H., Ishikawa, F., Yokokura, T., Takahashi, M., Sugimura, T., and Wakabayashi, K. 2003. Suppression of Helicobacter pylori-induced gastritis by green tea extract in Mongolian gerbils. Biochem. Biophys. Res. Commun. 310, 715–719.

    PubMed  CAS  Google Scholar 

  • Matsuzaki, K. 1998. Magainins as paradigm for the mode of action of pore forming polypeptides. Biochim. Biophys. Acta 1376, 391–400.

    PubMed  CAS  Google Scholar 

  • McGee, D.J., Coker, C., Testerman, T.L., Harro, J.M., Gibson, S.V., and Mobley, H.L. 2002. The Helicobacter pylori flbA flagellar biosynthesis and regulatory gene is required for motility and virulence and modulates urease of H. pylori and Proteus mirabilis. J. Med. Microbiol. 51, 958–970.

    PubMed  CAS  Google Scholar 

  • McGee, D.J. and Mobley, H.L. 1999. Mechanisms of Helicobacter pylori infection: bacterial factors. Curr. Top Microbiol. Immunol. 241, 155–180.

    PubMed  CAS  Google Scholar 

  • Mobley, H.L., Island, M.D., and Hausinger, R.P. 1995. Molecular biology of microbial ureases. Microbiol. Rev. 59, 451–480.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Molina-Infante, J., Romano, M., Fernandez-Bermejo, M., Federico, A., Gravina, A.G., Pozzati, L., Garcia-Abadia, E., Vinagre-Rodriguez, G., Martinez-Alcala, C., Hernandez-Alonso, M., and et al. 2013. Optimized nonbismuth quadruple therapies cure most patients with Helicobacter pylori infection in populations with high rates of antibiotic resistance. Gastroenterology 145, 121–128.

    PubMed  CAS  Google Scholar 

  • Molnar, P., Deli, J., Tanaka, T., Kann, Y., Tani, S., Gyemant, N., Molnar, J., and Kawase, M. 2010. Carotenoids with anti-Helicobacter pylori activity from Golden delicious apple. Phytother. Res. 24, 644–648.

    PubMed  CAS  Google Scholar 

  • Molnar, P., Kawase, M., Satoh, K., Sohara, Y., Tanaka, T., Tani, S., Sakagami, H., Nakashima, H., Motohashi, N., Gyemant, N., and Molnar, J. 2005. Biological activity of carotenoids in red paprika, Valencia orange and Golden delicious apple. Phytother. Res. 19, 700–707.

    PubMed  CAS  Google Scholar 

  • Moon, J.K., Kim, J.R., Ahn, Y.J., and Shibamoto, T. 2010. Analysis and anti-Helicobacter activity of sulforaphane and related compounds present in broccoli (Brassica oleracea L.) sprouts. J. Agric Food Chem. 58, 6672–6677.

    PubMed  CAS  Google Scholar 

  • Nanji, A.A., Jokelainen, K., Tipoe, G.L., Rahemtulla, A., Thomas, P., and Dannenberg, A.J. 2003. Curcumin prevents alcohol-induced liver disease in rats by inhibiting the expression of NF-kappa B-dependent genes. Am. J. Physiol. Gastrointest Liver Physiol. 284, G321–327.

    PubMed  CAS  Google Scholar 

  • Nanjundaiah, S.M., Annaiah, H.N., and Dharmesh, S.M. 2011. Gastroprotective effect of ginger rhizome (Zingiber officinale) extract: role of gallic acid and cinnamic acid in H(+), K(+)-ATPase/H. pylori inhibition and anti-oxidative mechanism. Evid. Based Complement. Alternat. Med. 2011, 249487.

    PubMed  PubMed Central  Google Scholar 

  • Nardone, G. 2000. Risk factors for cancer development in Helicobacter pylori gastritis. Dig. Liver Dis. 32Suppl 3, S190–192.

    PubMed  Google Scholar 

  • National Institute of Allergy and Infectious Diseases (NIAID). 2010. posting date. Dose escalation study of SQ109 in healthy adult volunteers. US National Institutes of Health, ClinicalTrials. gov online. ClinicalTrials.gov identifier NCT00866190. Available from URL: http://www.clinicaltrials.gov [Accessed 2010 Jun 28] [Online.]

    Google Scholar 

  • Ndip, R.N., Malange Takang, A.E., Echakachi, C.M., Malongue, A., Akoachere, J.F., Ndip, L.M., and Luma, H.N. 2007. In-vitro antimicrobial activity of selected honeys on clinical isolates of Helicobacter pylori. Afr. Health Sci. 7, 228–232.

    PubMed  PubMed Central  Google Scholar 

  • Nicoll, R. and Henein, M.Y. 2009. Ginger (Zingiber officinale Roscoe): a hot remedy for cardiovascular disease? Int. J. Cardiol. 131, 408–409.

    PubMed  Google Scholar 

  • Nikaido, H. 2003. Molecular basis of bacterial outer membrane permeability revisited. Microbiol. Mol. Biol. Rev. 67, 593–656.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Nir, Y., Potasman, I., Stermer, E., Tabak, M., and Neeman, I. 2000. Controlled trial of the effect of cinnamon extract on Helicobacter pylori. Helicobacter 5, 94–97.

    PubMed  CAS  Google Scholar 

  • Nishimori, I., Minakuchi, T., Kohsaki, T., Onishi, S., Takeuchi, H., Vullo, D., Scozzafava, A., and Supuran, C.T. 2007. Carbonic anhydrase inhibitors: the beta-carbonic anhydrase from Helicobacter pylori is a new target for sulfonamide and sulfamate inhibitors. Bioorg. Med. Chem. Lett. 17, 3585–3594.

    PubMed  CAS  Google Scholar 

  • Njume, C., Afolayan, A.J., Green, E., and Ndip, R.N. 2011. Volatile compounds in the stem bark of Sclerocarya birrea (Anacardiaceae) possess antimicrobial activity against drug-resistant strains of Helicobacter pylori. Int. J. Antimicrob. Agents 38, 319–324.

    PubMed  CAS  Google Scholar 

  • Nolan, K.J., McGee, D.J., Mitchell, H.M., Kolesnikow, T., Harro, J.M., O’Rourke, J., Wilson, J.E., Danon, S.J., Moss, N.D., Mobley, H.L., and et al. 2002. In vivo behavior of a Helicobacter pylori SS1 nixA mutant with reduced urease activity. Infect. Immun. 70, 685–691.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Nuding, S., Gersemann, M., Hosaka, Y., Konietzny, S., Schaefer, C., Beisner, J., Schroeder, B.O., Ostaff, M.J., Saigenji, K., Ott, G., and et al. 2013. Gastric antimicrobial peptides fail to eradicate Helicobacter pylori infection due to selective induction and resistance. PLoS One 8, e73867.

    PubMed  CAS  PubMed Central  Google Scholar 

  • O’Gara, E.A., Maslin, D.J., Nevill, A.M., and Hill, D.J. 2008. The effect of simulated gastric environments on the anti-Helicobacter activity of garlic oil. J. Appl. Microbiol. 104, 1324–1331.

    PubMed  Google Scholar 

  • Oh, T.Y., Yeo, M., Han, S.U., Cho, Y.K., Kim, Y.B., Chung, M.H., Kim, Y.S., Cho, S.W., and Hahm, K.B. 2005. Synergism of Helicobacter pylori infection and stress on the augmentation of gastric mucosal damage and its prevention with alpha-tocopherol. Free Radic. Biol. Med. 38, 1447–1457.

    PubMed  CAS  Google Scholar 

  • Okeleye, B.I., Bessong, P.O., and Ndip, R.N. 2011. Preliminary phytochemical screening and in vitro anti-Helicobacter pylori activity of extracts of the stem bark of Bridelia micrantha (Hochst., Baill., Euphorbiaceae). Molecules 16, 6193–6205.

    PubMed  CAS  Google Scholar 

  • Park, B.S., Lee, H.K., Lee, S.E., Piao, X.L., Takeoka, G.R., Wong, R.Y., Ahn, Y.J., and Kim, J.H. 2006. Antibacterial activity of Tabebuia impetiginosa Martius ex DC (Taheebo) against Helicobacter pylori. J. Ethnopharmacol. 105, 255–262.

    PubMed  CAS  Google Scholar 

  • Park, S., Yeo, M., Jin, J.H., Lee, K.M., Kim, S.S., Choi, S.Y., and Hahm, K.B. 2007. Inhibitory activities and attenuated expressions of 5-LOX with red ginseng in Helicobacter pylori-infected gastric epithelial cells. Dig. Dis. Sci. 52, 973–982.

    PubMed  Google Scholar 

  • Parsonnet, J. 1993. Helicobacter pylori and gastric cancer. Gastroenterol. Clin. North Am. 22, 89–104.

    PubMed  CAS  Google Scholar 

  • Peek, R.M.Jr. and Blaser, M.J. 1997. Pathophysiology of Helicobacter pylori-induced gastritis and peptic ulcer disease. Am. J. Med. 102, 200–207.

    PubMed  Google Scholar 

  • Peschel, A. 2002. How do bacteria resist human antimicrobial peptides? Trends Microbiol. 10, 179–186.

    PubMed  CAS  Google Scholar 

  • Peschel, A., Jack, R.W., Otto, M., Collins, L.V., Staubitz, P., Nicholson, G., Kalbacher, H., Nieuwenhuizen, W.F., Jung, G., Tarkowski, A., and et al. 2001. Staphylococcus aureus resistance to human defensins and evasion of neutrophil killing via the novel virulence factor MprF is based on modification of membrane lipids with l-lysine. J. Exp. Med. 193, 1067–1076.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Posadzki, P., Watson, L., and Ernst, E. 2013. Contamination and adulteration of herbal medicinal products (HMPs): an overview of systematic reviews. Eur. J. Clin. Pharmacol. 69, 295–307.

    PubMed  Google Scholar 

  • Pounder, R.E. and Ng, D. 1995. The prevalence of Helicobacter pylori infection in different countries. Aliment Pharmacol. Ther. 9Suppl 2, 33–39.

    PubMed  Google Scholar 

  • Pozharitskaya, O.N., Shikov, A.N., Makarova, M.N., Kosman, V.M., Faustova, N.M., Tesakova, S.V., Makarov, V.G., and Galambosi, B. 2010. Anti-inflammatory activity of a HPLC-fingerprinted aqueous infusion of aerial part of Bidens tripartita L. Phytomedicine 17, 463–468.

    PubMed  CAS  Google Scholar 

  • Protopopova, M., Hanrahan, C., Nikonenko, B., Samala, R., Chen, P., Gearhart, J., Einck, L., and Nacy, C.A. 2005. Identification of a new antitubercular drug candidate, SQ109, from a combinatorial library of 1,2-ethylenediamines. J. Antimicrob. Chemother. 56, 968–974.

    PubMed  CAS  Google Scholar 

  • Queiroz, D.M., Dani, R., Silva, L.D., Santos, A., Moreira, L.S., Rocha, G.A., Correa, P.R., Reis, L.F., Nogueira, A.M., Alvares Cabral, M.M., and et al. 2002. Factors associated with treatment failure of Helicobacter pylori infection in a developing country. J. Clin. Gastroenterol. 35, 315–320.

    PubMed  CAS  Google Scholar 

  • Radzishevsky, I.S., Kovachi, T., Porat, Y., Ziserman, L., Zaknoon, F., Danino, D., and Mor, A. 2008. Structure-activity relationships of antibacterial acyl-lysine oligomers. Chem. Biol. 15, 354–362.

    PubMed  CAS  Google Scholar 

  • Radzishevsky, I.S., Rotem, S., Bourdetsky, D., Navon-Venezia, S., Carmeli, Y., and Mor, A. 2007. Improved antimicrobial peptides based on acyl-lysine oligomers. Nat. Biotechnol. 25, 657–659.

    PubMed  CAS  Google Scholar 

  • Rao, Y.K., Fang, S.H., Hsieh, S.C., Yeh, T.H., and Tzeng, Y.M. 2009. The constituents of Anisomeles indica and their anti-inflammatory activities. J. Ethnopharmacol. 121, 292–296.

    PubMed  CAS  Google Scholar 

  • Romero, C., Medina, E., Vargas, J., Brenes, M., and De Castro, A. 2007. In vitro activity of olive oil polyphenols against Helicobacter pylori. J. Agric. Food Chem. 55, 680–686.

    PubMed  CAS  Google Scholar 

  • Rotem, S. and Mor, A. 2009. Antimicrobial peptide mimics for improved therapeutic properties. Biochim. Biophys. Acta. 1788, 1582–1592.

    PubMed  CAS  Google Scholar 

  • Rotem, S., Radzishevsky, I.S., Bourdetsky, D., Navon-Venezia, S., Carmeli, Y., and Mor, A. 2008. Analogous oligo-acyl-lysines with distinct antibacterial mechanisms. FASEB J. 22, 2652–2661.

    PubMed  CAS  Google Scholar 

  • Rotem, S., Raz, N., Kashi, Y., and Mor, A. 2010. Bacterial capture by peptide-mimetic oligoacyllysine surfaces. Appl. Environ. Microbiol. 76, 3301–3307.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Rowland, M. and Drumm, B. 1995. Helicobacter pylori infection and peptic ulcer disease in children. Curr. Opin. Pediatr. 7, 553–559.

    PubMed  CAS  Google Scholar 

  • Rozza, A.L., Moraes Tde, M., Kushima, H., Tanimoto, A., Marques, M.O., Bauab, T.M., Hiruma-Lima, C.A., and Pellizzon, C.H. 2011. Gastroprotective mechanisms of Citrus lemon (Rutaceae) essential oil and its majority compounds limonene and beta-pinene: involvement of heat-shock protein-70, vasoactive intestinal peptide, glutathione, sulfhydryl compounds, nitric oxide and prostaglandin E. Chem. Biol. Interact. 189, 82–89.

    PubMed  CAS  Google Scholar 

  • Ruggiero, P., Rossi, G., Tombola, F., Pancotto, L., Lauretti, L., Del Giudice, G., and Zoratti, M. 2007. Red wine and green tea reduce H. pylori- or VacA-induced gastritis in a mouse model. World J. Gastroenterol. 13, 349–354.

    PubMed  Google Scholar 

  • Sarig, H., Rotem, S., Ziserman, L., Danino, D., and Mor, A. 2008. Impact of self-assembly properties on antibacterial activity of short acyl-lysine oligomers. Antimicrob. Agents Chemother. 52, 4308–4314.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Schmidtchen, A., Frick, I.M., Andersson, E., Tapper, H., and Bjorck, L. 2002. Proteinases of common pathogenic bacteria degrade and inactivate the antibacterial peptide LL-37. Mol. Microbiol. 46, 157–168.

    PubMed  CAS  Google Scholar 

  • Sekiguchi, H., Takabayashi, F., Irie, K., and Murakami, A. 2012. Auraptene attenuates gastritis via reduction of Helicobacter pylori colonization and pro-inflammatory mediator production in C57BL/6 mice. J. Med. Food 15, 658–663.

    PubMed  CAS  Google Scholar 

  • Sequella 2013, posting date. SQ109 for the Treatment of Helicobacter pylori infection-Clinical Development Status: Phase 2 Trials. Sequella. Accessed March 07, 2013 [Online.]

    Google Scholar 

  • Sezikli, M., Cetinkaya, Z.A., Sezikli, H., Guzelbulut, F., Tiftikci, A., Ince, A.T., Gokden, Y., Yasar, B., Atalay, S., and Kurdas, O.O. 2009. Oxidative stress in Helicobacter pylori infection: does supplementation with vitamins C and E increase the eradication rate? Helicobacter 14, 280–285.

    PubMed  CAS  Google Scholar 

  • Shafer, W.M., Qu, X., Waring, A.J., and Lehrer, R.I. 1998. Modulation of Neisseria gonorrhoeae susceptibility to vertebrate antibacterial peptides due to a member of the resistance/nodulation/division efflux pump family. Proc. Natl. Acad. Sci. USA 95, 1829–1833.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Shen, C.J., Kuo, T.Y., Lin, C.C., Chow, L.P., and Chen, W.J. 2010. Proteomic identification of membrane proteins regulating antimicrobial peptide resistance in Vibrio parahaemolyticus. J. Appl. Microbiol. 108, 1398–1407.

    PubMed  CAS  Google Scholar 

  • Shikov, A.N., Pozharitskaya, O.N., Makarov, V.G., and Kvetnaya, A.S. 2008. Antibacterial activity of Chamomilla recutita oil extract against Helicobacter pylori. Phytother. Res. 22, 252–253.

    PubMed  Google Scholar 

  • Silverio, M.S., Del-Vechio-Vieira, G., Pinto, M.A., Alves, M.S., and Sousa, O.V. 2013. Chemical composition and biological activities of essential oils of Eremanthus erythropappus (DC) McLeisch (Asteraceae). Molecules 18, 9785–9796.

    PubMed  CAS  Google Scholar 

  • Sivam, G.P. 2001. Protection against Helicobacter pylori and other bacterial infections by garlic. J. Nutr. 131, 1106S–1108S.

    PubMed  CAS  Google Scholar 

  • Sivam, G.P., Lampe, J.W., Ulness, B., Swanzy, S.R., and Potter, J.D. 1997. Helicobacter pylori—in vitro susceptibility to garlic (Allium sativum) extract. Nutr. Cancer 27, 118–121.

    PubMed  CAS  Google Scholar 

  • Song, J.M. and Seong, B.L. 2007. Tea catechins as a potential alternative anti-infectious agent. Expert. Rev. Anti. Infect. Ther. 5, 497–506.

    PubMed  CAS  Google Scholar 

  • Srikanta, B., Siddaraju, M., and Dharmesh, S. 2007. A novel phenol-bound pectic polysaccharide from Decalepis hamiltonii with multi-step ulcer preventive activity. World J. Gastroenterol. 13, 5196–5207.

    PubMed  CAS  Google Scholar 

  • Stoicov, C., Saffari, R., and Houghton, J. 2009. Green tea inhibits Helicobacter growth in vivo and in vitro. Int. J. Antimicrob. Agents 33, 473–478.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Suerbaum, S. and Josenhans, C. 2007. Helicobacter pylori evolution and phenotypic diversification in a changing host. Nat. Rev. Microbiol. 5, 441–452.

    PubMed  CAS  Google Scholar 

  • Tabak, M., Armon, R., and Neeman, I. 1999. Cinnamon extracts’ inhibitory effect on Helicobacter pylori. J. Ethnopharmacol. 67, 269–277.

    PubMed  CAS  Google Scholar 

  • Tan, P.V., Boda, M., and Etoa, F.X. 2010. In vitro and in vivo anti-Helicobacter/Campylobacter activity of the aqueous extract of Enantia chlorantha. Pharm. Biol. 48, 349–356.

    PubMed  Google Scholar 

  • Thompson, L., Cockayne, A., and Spiller, R.C. 1994. Inhibitory effect of polyunsaturated fatty acids on the growth of Helicobacter pylori: a possible explanation of the effect of diet on peptic ulceration. Gut 35, 1557–1561.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Tombola, F., Campello, S., De Luca, L., Ruggiero, P., Del Giudice, G., Papini, E., and Zoratti, M. 2003. Plant polyphenols inhibit VacA, a toxin secreted by the gastric pathogen Helicobacter pylori. FEBS Lett. 543, 184–189.

    PubMed  CAS  Google Scholar 

  • Tran, A.X., Whittimore, J.D., Wyrick, P.B., McGrath, S.C., Cotter, R.J., and Trent, M.S. 2006. The lipid A 1-phosphatase of Helicobacter pylori is required for resistance to the antimicrobial peptide polymyxin. J. Bacteriol. 188, 4531–4541.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Uehara, N., Yagihashi, A., Kondoh, K., Tsuji, N., Fujita, T., Hamada, H., and Watanabe, N. 2003. Human beta-defensin-2 induction in Helicobacter pylori-infected gastric mucosal tissues: antimicrobial effect of overexpression. J. Med. Microbiol. 52, 41–45.

    PubMed  CAS  Google Scholar 

  • Urr, P. 2003. Medicinal Plants and Their Utilization. United Nations Industrial Development Organization (UNIDO) and the International Centre for Scienceand High Technology (ICS). UNIDO Publication, ICS-UNIDO, AREA Science Park, Padriciano 99, 34012 Trieste, Italy.

    Google Scholar 

  • Ustun, O., Ozcelik, B., Akyon, Y., Abbasoglu, U., and Yesilada, E. 2006. Flavonoids with anti-Helicobacter pylori activity from Cistus laurifolius leaves. J. Ethnopharmacol. 108, 457–461.

    PubMed  Google Scholar 

  • van Heijenoort, J. 2001. Recent advances in the formation of the bacterial peptidoglycan monomer unit. Nat. Prod. Rep. 18, 503–519.

    PubMed  Google Scholar 

  • Varbanova, M., Schulz, C., and Malfertheiner, P. 2011. Helicobacter pylori and other gastric bacteria. Dig. Dis. 29, 562–569.

    PubMed  CAS  Google Scholar 

  • Versalovic, J., Shortridge, D., Kibler, K., Griffy, M.V., Beyer, J., Flamm, R.K., Tanaka, S.K., Graham, D.Y., and Go, M.F. 1996. Mutations in 23S rRNA are associated with clarithromycin resistance in Helicobacter pylori. Antimicrob. Agents Chemother. 40, 477–480.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Vitor, J.M. and Vale, F.F. 2011. Alternative therapies for Helicobacter pylori: probiotics and phytomedicine. FEMS Immunol. Med. Microbiol. 63, 153–164.

    PubMed  CAS  Google Scholar 

  • Warin, R., Chambers, W.H., Potter, D.M., and Singh, S.V. 2009. Prevention of mammary carcinogenesis in MMTV-neu mice by cruciferous vegetable constituent benzyl isothiocyanate. Cancer Res. 69, 9473–9480.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Warren, J.R. and Marshall, B. 1983. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet 1, 1273–1275.

    Google Scholar 

  • WHO. 1994. Schistosomes, Liver Flukes and Helicobacter pylori. Monographs on the evaluation of carcinogenic risks to humans. Lyon. (IARC) 61, 177–240.

    Google Scholar 

  • Wittschier, N., Faller, G., and Hensel, A. 2007a. An extract of Pelargonium sidoides (EPs 7630) inhibits in situ adhesion of Helicobacter pylori to human stomach. Phytomedicine 14, 285–288.

    PubMed  CAS  Google Scholar 

  • Wittschier, N., Lengsfeld, C., Vorthems, S., Stratmann, U., Ernst, J.F., Verspohl, E.J., and Hensel, A. 2007b. Large molecules as anti-adhesive compounds against pathogens. J. Pharm. Pharmacol. 59, 777–786.

    PubMed  CAS  Google Scholar 

  • Wong, W.M., Gu, Q., Wang, W.H., Fung, F.M., Berg, D.E., Lai, K.C., Xia, H.H., Hu, W.H., Chan, C.K., Chan, A.O., and et al. 2003. Effects of primary metronidazole and clarithromycin resistance to Helicobacter pylori on omeprazole, metronidazole, and clarithromycin triple-therapy regimen in a region with high rates of metronidazole resistance. Clin. Infect. Dis. 37, 882–889.

    PubMed  CAS  Google Scholar 

  • Yanagawa, Y., Yamamoto, Y., Hara, Y., and Shimamura, T. 2003. A combination effect of epigallocatechin gallate, a major compound of green tea catechins, with antibiotics on Helicobacter pylori growth in vitro. Curr. Microbiol. 47, 244–249.

    PubMed  CAS  Google Scholar 

  • Yanaka, A. 2011. Sulforaphane enhances protection and repair of gastric mucosa against oxidative stress in vitro, and demonstrates anti-inflammatory effects on Helicobacter pylori-infected gastric mucosae in mice and human subjects. Curr. Pharm. Des. 17, 1532–1540.

    PubMed  CAS  Google Scholar 

  • Yanaka, A., Fahey, J.W., Fukumoto, A., Nakayama, M., Inoue, S., Zhang, S., Tauchi, M., Suzuki, H., Hyodo, I., and Yamamoto, M. 2009. Dietary sulforaphane-rich broccoli sprouts reduce colonization and attenuate gastritis in Helicobacter pylori-infected mice and humans. Cancer Prev. Res. (Phila). 2, 353–360.

    CAS  Google Scholar 

  • Zaknoon, F., Sarig, H., Rotem, S., Livne, L., Ivankin, A., Gidalevitz, D., and Mor, A. 2009. Antibacterial properties and mode of action of a short acyl-lysyl oligomer. Antimicrob. Agents Chemother. 53, 3422–3429.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Zasloff, M. 2002. Antimicrobial peptides of multicellular organisms. Nature 415, 389–395.

    PubMed  CAS  Google Scholar 

  • Zhang, L., Liu, W., Hu, T., Du, L., Luo, C., Chen, K., Shen, X., and Jiang, H. 2008. Structural basis for catalytic and inhibitory mechanisms of beta-hydroxyacyl-acyl carrier protein dehydratase (FabZ). J. Biol. Chem. 283, 5370–5379.

    PubMed  CAS  Google Scholar 

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Makobongo, M.O., Gilbreath, J.J. & Merrell, D.S. Nontraditional therapies to treat Helicobacter pylori infection. J Microbiol. 52, 259–272 (2014). https://doi.org/10.1007/s12275-014-3603-5

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