1887

Abstract

Citrus limonoids are unique secondary metabolites, characterized by a triterpenoid skeleton with a furan ring. Studies have demonstrated beneficial health properties of limonoids. In addition, certain citrus limonoids play a role in plant defence against insect pests. In the present study, five limonoids were purified from sour orange and evaluated for their ability to inhibit cell–cell signalling. The purified limonoids were tested for their ability to interfere with cell–cell signalling and biofilm formation in . Isolimonic acid, deacetylnomilinic acid glucoside and ichangin demonstrated significant inhibition of autoinducer-mediated cell–cell signalling and biofilm formation. Furthermore, isolimonic acid and ichangin treatment resulted in induced expression of the response regulator gene . In addition, promoter activity was not affected by isolimonic acid or ichangin. Therefore, the ability of isolimonic acid and ichangin to interfere with cell–cell signalling and biofilm formation seems to stem from the modulation of expression. The results suggest that isolimonic acid and ichangin are potent modulators of bacterial cell–cell signalling.

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2011-01-01
2019-12-08
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References

  1. Anetzberger, C., Pirch, T. & Jung, K. ( 2009; ). Heterogeneity in quorum sensing-regulated bioluminescence of Vibrio harveyi. Mol Microbiol 73, 267–277.[CrossRef]
    [Google Scholar]
  2. Atawodi, S. & Atawodi, J. ( 2009; ). Azadirachta indica (neem): a plant of multiple biological and pharmacological activities. Phytochem Rev 8, 601–620.[CrossRef]
    [Google Scholar]
  3. Bassler, B. L. & Losick, R. ( 2006; ). Bacterially speaking. Cell 125, 237–246.[CrossRef]
    [Google Scholar]
  4. Bassler, B. L., Greenberg, E. P. & Stevens, A. M. ( 1997; ). Cross-species induction of luminescence in the quorum-sensing bacterium Vibrio harveyi. J Bacteriol 179, 4043–4045.
    [Google Scholar]
  5. Battinelli, L., Mengoni, F., Lichtner, M., Mazzanti, G., Saija, A., Mastroianni, C. M. & Vullo, V. ( 2003; ). Effect of limonin and nomilin on HIV-1 replication on infected human mononuclear cells. Planta Med 69, 910–913.[CrossRef]
    [Google Scholar]
  6. Bentley, M. D., Rajab, M. S., Mendel, M. J. & Alford, A. R. ( 1990; ). Limonoid model insect antifeedants. J Agric Food Chem 38, 1400–1403.[CrossRef]
    [Google Scholar]
  7. Champagne, D. E., Koul, O., Isman, M. B., Scudder, G. G. E. & Neil Towers, G. H. ( 1992; ). Biological activity of limonoids from the rutales. Phytochemistry 31, 377–394.[CrossRef]
    [Google Scholar]
  8. Cowan, M. M. ( 1999; ). Plant products as antimicrobial agents. Clin Microbiol Rev 12, 564–582.
    [Google Scholar]
  9. Erickson, D. L., Endersby, R., Kirkham, A., Stuber, K., Vollman, D. D., Rabin, H. R., Mitchell, I. & Storey, D. G. ( 2002; ). Pseudomonas aeruginosa quorum-sensing systems may control virulence factor expression in the lungs of patients with cystic fibrosis. Infect Immun 70, 1783–1790.[CrossRef]
    [Google Scholar]
  10. Freeman, J. A. & Bassler, B. L. ( 1999a; ). Sequence and function of LuxU: a two-component phosphorelay protein that regulates quorum sensing in Vibrio harveyi. J Bacteriol 181, 899–906.
    [Google Scholar]
  11. Freeman, J. A. & Bassler, B. L. ( 1999b; ). A genetic analysis of the function of LuxO, a two-component response regulator involved in quorum sensing in Vibrio harveyi. Mol Microbiol 31, 665–677.[CrossRef]
    [Google Scholar]
  12. Gershenzon, J. & Dudareva, N. ( 2007; ). The function of terpene natural products in the natural world. Nat Chem Biol 3, 408–414.[CrossRef]
    [Google Scholar]
  13. Girennavar, B., Cepeda, M. L., Soni, K. A., Vikram, A., Jesudhasan, P., Jayaprakasha, G. K., Pillai, S. D. & Patil, B. S. ( 2008; ). Grapefruit juice and its furocoumarins inhibits autoinducer signaling and biofilm formation in bacteria. Int J Food Microbiol 125, 204–208.[CrossRef]
    [Google Scholar]
  14. Givskov, M., de Nys, R., Manefield, M., Gram, L., Maximilien, R., Eberl, L., Molin, S., Steinberg, P. & Kjelleberg, S. ( 1996; ). Eukaryotic interference with homoserine lactone-mediated prokaryotic signalling. J Bacteriol 178, 6618–6622.
    [Google Scholar]
  15. Guthri, N., Morley, K., Hasegawa, S., Manner Gary, D. & Vandenberg, T. ( 2000; ). Inhibition of human breast cancer cells by citrus limonoids. In Citrus Limonoids, pp. 164–174. Washington, DC. : American Chemical Society.
    [Google Scholar]
  16. Havsteen, B. H. ( 2002; ). The biochemistry and medical significance of the flavonoids. Pharmacol Ther 96, 67–202.[CrossRef]
    [Google Scholar]
  17. Henke, J. M. & Bassler, B. L. ( 2004; ). Three parallel quorum-sensing systems regulate gene expression in Vibrio harveyi. J Bacteriol 186, 6902–6914.[CrossRef]
    [Google Scholar]
  18. Hentzer, M., Wu, H., Andersen, J. B., Riedel, K., Rasmussen, T. B., Bagge, N., Kumar, N., Schembri, M. A., Song, Z. & other authors ( 2003; ). Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. EMBO J 22, 3803–3815.[CrossRef]
    [Google Scholar]
  19. Huber, B., Eberl, L., Feucht, W. & Polster, J. ( 2003; ). Influence of polyphenols on bacterial biofilm formation and quorum-sensing. Z Naturforsch C 58, 879–884.
    [Google Scholar]
  20. Jayaprakasha, G. K., Patil, B. S. & Bhat, N. G. ( 2006; ). A process for isolation of limonin glucoside and isoobacunoic acid glucoside from citrus seeds. USA patent application no. 60/74437.
  21. Lam, L. K. T., Li, Y. & Hasegawa, S. ( 1989; ). Effects of citrus limonoids on glutathione S-transferase activity in mice. J Agric Food Chem 37, 878–880.[CrossRef]
    [Google Scholar]
  22. Langenheim, J. H. ( 1994; ). Higher plant terpenoids: a phytocentric overview of their ecological roles. J Chem Ecol 20, 1223–1280.[CrossRef]
    [Google Scholar]
  23. Lenz, D. H., Mok, K. C., Lilley, B. N., Kulkarni, R. V., Wingreen, N. S. & Bassler, B. L. ( 2004; ). The small RNA chaperone Hfq and multiple small RNAs control quorum sensing in Vibrio harveyi and Vibrio cholerae. Cell 118, 69–82.[CrossRef]
    [Google Scholar]
  24. Lilley, B. N. & Bassler, B. L. ( 2000; ). Regulation of quorum sensing in Vibrio harveyi by LuxO and Sigma-54. Mol Microbiol 36, 940–954.[CrossRef]
    [Google Scholar]
  25. Lin, Y. H., Miyamoto, C. & Meighen, E. A. ( 2000; ). Cloning and functional studies of a luxO regulator LuxT from Vibrio harveyi. Biochim Biophys Acta 1494, 226–235.[CrossRef]
    [Google Scholar]
  26. Livak, K. J. & Schmittgen, T. D. ( 2001; ). Analysis of relative gene expression data using real-time quantitative PCR and the method. Methods 25, 402–408.[CrossRef]
    [Google Scholar]
  27. Lu, L., Hume, M. E. & Pillai, S. D. ( 2004; ). Autoinducer-2 like activity associated with foods and its interaction with food additives. J Food Prot 67, 1457–1462.
    [Google Scholar]
  28. Maier, V. P. & Grant, E. R. ( 1970; ). Specific thin-layer chromatography assay of limonin, a citrus bitter principle. J Agric Food Chem 18, 250–252.[CrossRef]
    [Google Scholar]
  29. Manefield, M., Rasmussen, T. B., Henzter, M., Andersen, J. B., Steinberg, P., Kjelleberg, S. & Givskov, M. ( 2002; ). Halogenated furanones inhibit quorum sensing through accelerated LuxR turnover. Microbiology 148, 1119–1127.
    [Google Scholar]
  30. Manners, G. D., Hasegawa, S., Barnett, R. D. & Wong, R. Y. ( 2000; ). LC-MS and NMR techniques for the analysis and characterization of Citrus limonoids. In Citrus Limonoids: Functional Chemicals in Agriculture and Foods, pp. 40–59. Edited by Berhow, M. A., Hasegawa, S. & Manners, G. D.. Washington, DC. : American Chemical Society.
    [Google Scholar]
  31. McIntosh, C. A. ( 2000; ). Quantification of limonin and limonoate A-ring monolactone during growth and development of citrus fruit and vegetative tissues by radioimmunoassay. In Citrus Limonoids: Functional Chemicals in Agriculture and Foods, pp. 73–95. Edited by Berhow, M. A., Hasegawa, S. & Manners, G. D.. Washington, DC. : American Chemical Society.
    [Google Scholar]
  32. McIntosh, C. A. & Mansell, R. L. ( 1983; ). Distribution of limonin during the growth and development of leaves and branches of Citrus paradisi. J Agric Food Chem 31, 319–325.[CrossRef]
    [Google Scholar]
  33. Miller, J. H. ( 1972; ). Assay for β-galactosidase. In Experiments in Molecular Genetics, pp. 352–355. Cold Spring Harbor, NY. : Cold Spring Harbor Laboratory.
    [Google Scholar]
  34. Miller, E. G., Porter, J. L., Binnie, W. H., Guo, I. Y. & Hasegawa, S. ( 2004; ). Further studies on the anticancer activity of citrus limonoids. J Agric Food Chem 52, 4908–4912.[CrossRef]
    [Google Scholar]
  35. Perez, J. L., Jayaprakasha, G. K., Valdivia, V., Munoz, D., Dandekar, D. V., Ahmad, H. & Patil, B. S. ( 2009; ). Limonin methoxylation influences the induction of glutathione S-transferase and quinone reductase. J Agric Food Chem 57, 5279–5286.[CrossRef]
    [Google Scholar]
  36. Persson, T., Hansen, T. H., Rasmussen, T. B., Skinderso, M. E., Givskov, M. & Nielsen, J. ( 2005; ). Rational design and synthesis of new quorum-sensing inhibitors derived from acylated homoserine lactones and natural products from garlic. Org Biomol Chem 3, 253–262.[CrossRef]
    [Google Scholar]
  37. Poulose, S. M., Harris, E. D. & Patil, B. S. ( 2005; ). Citrus limonoids induce apoptosis in human neuroblastoma cells and have radical scavenging activity. J Nutr 135, 870–877.
    [Google Scholar]
  38. Qin, Y., Luo, Z.-Q. & Farrand, S. K. ( 2004; ). Domains formed within the N-terminal region of the quorum-sensing activator TraR are required for transcriptional activation and direct interaction with RpoA from Agrobacterium. J Biol Chem 279, 40844–40851.[CrossRef]
    [Google Scholar]
  39. Rasmussen, T. B. & Givskov, M. ( 2006; ). Quorum sensing inhibitors: a bargain of effects. Microbiology 152, 895–904.[CrossRef]
    [Google Scholar]
  40. Rasmussen, T. B., Skindersoe, M. E., Bjarnsholt, T., Phipps, R. K., Christensen, K. B., Jensen, P. O., Andersen, J. B., Koch, B., Larsen, T. O. & other authors ( 2005; ). Identity and effects of quorum-sensing inhibitors produced by Penicillium species. Microbiology 151, 1325–1340.[CrossRef]
    [Google Scholar]
  41. Rozen, S. & Skaletsky, H. J. ( 2000; ). Primer3 on the WWW for general users and for biologist programmers. In Bioinformatics Methods and Protocols: Methods in Molecular Biology, pp. 365–386. Edited by Krawetz, S. & Misener, S.. Totowa, NJ. : Humana Press.
    [Google Scholar]
  42. Ruberto, G., Renda, A., Tringali, C., Napoli, E. M. & Simmonds, M. S. J. ( 2002; ). Citrus limonoids and their semisynthetic derivatives as antifeedant agents against Spodoptera frugiperda larvae. A structure–activity relationship study. J Agric Food Chem 50, 6766–6774.[CrossRef]
    [Google Scholar]
  43. Sambrook, J. & Russell, D. W. ( 2001; ). Molecular Cloning: a Laboratory Manual, 3rd edn. Cold Spring Harbor, NY. : Cold Spring Harbor Laboratory.
    [Google Scholar]
  44. Sircili, M. P., Walters, M., Trabulsi, L. R. & Sperandio, V. ( 2004; ). Modulation of enteropathogenic Escherichia coli virulence by quorum sensing. Infect Immun 72, 2329–2337.[CrossRef]
    [Google Scholar]
  45. Surette, M. G. & Bassler, B. L. ( 1998; ). Quorum sensing in Escherichia coli and Salmonella typhimurium. Proc Natl Acad Sci U S A 95, 7046–7050.[CrossRef]
    [Google Scholar]
  46. Svenningsen, S. L., Waters, C. M. & Bassler, B. L. ( 2008; ). A negative feedback loop involving small RNAs accelerates Vibrio cholerae's transition out of quorum-sensing mode. Genes Dev 22, 226–238.[CrossRef]
    [Google Scholar]
  47. Tanaka, T., Maeda, M., Kohno, H., Murakami, M., Kagami, S., Miyake, M. & Wada, K. ( 2001; ). Inhibition of azoxymethane-induced colon carcinogenesis in male F344 rats by the citrus limonoids obacunone and limonin. Carcinogenesis 22, 193–198.[CrossRef]
    [Google Scholar]
  48. Tian, Q., Miller, E. G., Ahmad, H., Tang, L. & Patil, B. S. ( 2001; ). Differential inhibition of human cancer cell proliferation by citrus limonoids. Nutr Cancer 40, 180–184.[CrossRef]
    [Google Scholar]
  49. Tu, K. C. & Bassler, B. L. ( 2007; ). Multiple small RNAs act additively to integrate sensory information and control quorum sensing in Vibrio harveyi. Genes Dev 21, 221–233.[CrossRef]
    [Google Scholar]
  50. Vanamala, J., Leonardi, T., Patil, B. S., Taddeo, S. S., Murphy, M. E., Pike, L. M., Chapkin, R. S., Lupton, J. R. & Turner, N. D. ( 2006; ). Suppression of colon carcinogenesis by bioactive compounds in grapefruit. Carcinogenesis 27, 1257–1265.[CrossRef]
    [Google Scholar]
  51. Vikram, A., Jayaprakasha, G. K. & Patil, B. S. ( 2007; ). Simultaneous determination of citrus limonoid aglycones and glucosides by high performance liquid chromatography. Anal Chim Acta 590, 180–186.[CrossRef]
    [Google Scholar]
  52. Vikram, A., Jayaprakasha, G. K., Jesudhasan, P. R., Pillai, S. D. & Patil, B. S. ( 2010a; ). Suppression of bacterial cell–cell signalling, biofilm formation and type III secretion system by citrus flavonoids. J Appl Microbiol 109, 515–527.
    [Google Scholar]
  53. Vikram, A., Jesudhasan, P. R., Jayaprakasha, G. K., Pillai, S. D. & Patil, B. S. ( 2010b; ). Grapefruit bioactive limonoids modulate E. coli O157 : H7 TTSS and biofilm. Int J Food Microbiol 140, 109–116.[CrossRef]
    [Google Scholar]
  54. Walters, M. & Sperandio, V. ( 2006; ). Autoinducer 3 and epinephrine signaling in the kinetics of locus of enterocyte effacement gene expression in enterohemorrhagic Escherichia coli. Infect Immun 74, 5445–5455.[CrossRef]
    [Google Scholar]
  55. Wang, X., Yao, X., Zhu, Z., Tang, T., Dai, K., Sadovskaya, I., Flahaut, S. & Jabbouri, S. ( 2009; ). Effect of berberine on Staphylococcus epidermidis biofilm formation. Int J Antimicrob Agents 34, 60–66.[CrossRef]
    [Google Scholar]
  56. Yu, J., Wang, L., Walzem, R. L., Miller, E. G., Pike, L. M. & Patil, B. S. ( 2005; ). Antioxidant activity of citrus limonoids, flavonoids, and coumarins. J Agric Food Chem 53, 2009–2014.[CrossRef]
    [Google Scholar]
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