1887

Abstract

The objective of this study was to screen for novel quorum-sensing inhibitors (QSIs) from traditional Chinese medicines (TCMs) that inhibit bacterial biofilm formation. Six of 46 active components found in TCMs were identified as putative QSIs based on molecular docking studies. Of these, three compounds inhibited biofilm formation by and at a concentration of 200 µM. A fourth compound (emodin) significantly inhibited biofilm formation at 20 µM and induced proteolysis of the quorum-sensing signal receptor TraR in at a concentration of 3–30 mM. Emodin also increased the activity of ampicillin against Therefore, emodin might be suitable for development into an antivirulence and antibacterial agent.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.024166-0
2011-12-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/jmm/60/12/1827.html?itemId=/content/journal/jmm/10.1099/jmm.0.024166-0&mimeType=html&fmt=ahah

References

  1. Adonizio A. L., Downum K., Bennett B. C., Mathee K. 2006; Anti-quorum sensing activity of medicinal plants in southern Florida. J Ethnopharmacol 105:427–435 [View Article][PubMed]
    [Google Scholar]
  2. Basu S., Ghosh A., Hazra B. 2005; Evaluation of the antibacterial activity of Ventilago madraspatana Gaertn., Rubia cordifolia Linn. and Lantana camara Linn.: isolation of emodin and physcion as active antibacterial agents. Phytother Res 19:888–894 [View Article][PubMed]
    [Google Scholar]
  3. Bergstrom C. T., Lo M., Lipsitch M. 2004; Ecological theory suggests that antimicrobial cycling will not reduce antimicrobial resistance in hospitals. Proc Natl Acad Sci U S A 101:13285–13290 [View Article][PubMed]
    [Google Scholar]
  4. Bjarnsholt T., Jensen P. Ø., Burmølle M., Hentzer M., Haagensen J. A., Hougen H. P., Calum H., Madsen K. G., Moser C. et al. other authors 2005; Pseudomonas aeruginosa tolerance to tobramycin, hydrogen peroxide and polymorphonuclear leukocytes is quorum-sensing dependent. Microbiology 151:373–383 [View Article][PubMed]
    [Google Scholar]
  5. Bottomley M. J., Muraglia E., Bazzo R., Carfì A. 2007; Molecular insights into quorum sensing in the human pathogen Pseudomonas aeruginosa from the structure of the virulence regulator LasR bound to its autoinducer. J Biol Chem 282:13592–13600 [View Article][PubMed]
    [Google Scholar]
  6. Boyen F., Eeckhaut V., Van Immerseel F., Pasmans F., Ducatelle R., Haesebrouck F. 2009; Quorum sensing in veterinary pathogens: mechanisms, clinical importance and future perspectives. Vet Microbiol 135:187–195 [View Article][PubMed]
    [Google Scholar]
  7. Cha T. L., Qiu L., Chen C. T., Wen Y., Hung M. C. 2005; Emodin down-regulates androgen receptor and inhibits prostate cancer cell growth. Cancer Res 65:2287–2295 [View Article][PubMed]
    [Google Scholar]
  8. Chang P. C., Li H. Y., Tang H. J., Liu J. W., Wang J. J., Chuang Y. C. 2007; In vitro synergy of baicalein and gentamicin against vancomycin-resistant Enterococcus. . J Microbiol Immunol Infect 40:56–61[PubMed]
    [Google Scholar]
  9. Chen Q., Zhao Y., Cheng Z., Xu Y., Yu C. 2008; Establishment of a cell-based assay for examining the expression of tumor necrosis factor alpha (TNF-α) gene. Appl Microbiol Biotechnol 80:357–363 [View Article][PubMed]
    [Google Scholar]
  10. Choo J. H., Rukayadi Y., Hwang J. K. 2006; Inhibition of bacterial quorum sensing by vanilla extract. Lett Appl Microbiol 42:637–641[PubMed]
    [Google Scholar]
  11. Costerton J. W., Lewandowski Z., DeBeer D., Caldwell D., Korber D., James G. 1994; Biofilms, the customized microniche. J Bacteriol 176:2137–2142[PubMed]
    [Google Scholar]
  12. Costerton J. W., Lewandowski Z., Caldwell D. E., Korber D. R., Lappin-Scott H. M. 1995; Microbial biofilms. Annu Rev Microbiol 49:711–745 [View Article][PubMed]
    [Google Scholar]
  13. Donlan R. M., Costerton J. W. 2002; Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev 15:167–193 [View Article][PubMed]
    [Google Scholar]
  14. Drenkard E. 2003; Antimicrobial resistance of Pseudomonas aeruginosa biofilms. Microbes Infect 5:1213–1219 [View Article][PubMed]
    [Google Scholar]
  15. Fouhy Y., Scanlon K., Schouest K., Spillane C., Crossman L., Avison M. B., Ryan R. P., Dow J. M. 2007; Diffusible signal factor-dependent cell-cell signaling and virulence in the nosocomial pathogen Stenotrophomonas maltophilia. . J Bacteriol 189:4964–4968 [View Article][PubMed]
    [Google Scholar]
  16. Frederiksen B., Koch C., Høiby N. 1997; Antibiotic treatment of initial colonization with Pseudomonas aeruginosa postpones chronic infection and prevents deterioration of pulmonary function in cystic fibrosis. Pediatr Pulmonol 23:330–335 [View Article][PubMed]
    [Google Scholar]
  17. Fu Z. Y., Han J. X., Huang H. Y. 2007; Effects of emodin on gene expression profile in small cell lung cancer NCI-H446 cells. Chin Med J (Engl) 120:1710–1715[PubMed]
    [Google Scholar]
  18. Fujita M., Shiota S., Kuroda T., Hatano T., Yoshida T., Mizushima T., Tsuchiya T. 2005; Remarkable synergies between baicalein and tetracycline, and baicalein and beta-lactams against methicillin-resistant Staphylococcus aureus . Microbiol Immunol 49:391–396[PubMed] [CrossRef]
    [Google Scholar]
  19. Fuqua C., Winans S. C. 1996; Localization of OccR-activated and TraR-activated promoters that express two ABC-type permeases and the traR gene of Ti plasmid pTiR10. Mol Microbiol 20:1199–1210 [View Article][PubMed]
    [Google Scholar]
  20. Furci L. M., Lopes P., Eakanunkul S., Zhong S. Jr, MacKerell A. D. Jr, Wilks A. 2007; Inhibition of the bacterial heme oxygenases from Pseudomonas aeruginosa and Neisseria meningitidis: novel antimicrobial targets. J Med Chem 50:3804–3813 [View Article][PubMed]
    [Google Scholar]
  21. Ganin H., Tang X., Meijler M. M. 2009; Inhibition of Pseudomonas aeruginosa quorum sensing by AI-2 analogs. Bioorg Med Chem Lett 19:3941–3944 [View Article][PubMed]
    [Google Scholar]
  22. Givskov M., de Nys R., Manefield M., Gram L., Maximilien R., Eberl L., Molin S., Steinberg P. D., Kjelleberg S. 1996; Eukaryotic interference with homoserine lactone-mediated prokaryotic signalling. J Bacteriol 178:6618–6622[PubMed]
    [Google Scholar]
  23. Gjødsbøl K., Christensen J. J., Karlsmark T., Jørgensen B., Klein B. M., Krogfelt K. A. 2006; Multiple bacterial species reside in chronic wounds: a longitudinal study. Int Wound J 3:225–231 [View Article][PubMed]
    [Google Scholar]
  24. Hentzer M., Wu H., Andersen J. B., Riedel K., Rasmussen T. B., Bagge N., Kumar N., Schembri M. A., Song Z. et al. other authors 2003; Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. EMBO J 22:3803–3815 [View Article][PubMed]
    [Google Scholar]
  25. Huang Y. H., Zhen Y. S. 2001; [Rhein induces apoptosis in cancer cells and shows synergy with mitomycin]. Yao Xue Xue Bao 36:334–338[PubMed]
    [Google Scholar]
  26. Huang Y., Tsang S. Y., Yao X., Chen Z. Y. 2005; Biological properties of baicalein in cardiovascular system. Curr Drug Targets Cardiovasc Haematol Disord 5:177–184 [View Article][PubMed]
    [Google Scholar]
  27. Huang Z. W., Chen G. C., Shi P. 2008; Emodin-induced apoptosis in human breast cancer BCap-37 cells through the mitochondrial signaling pathway. Arch Pharm Res 31:742–748 [View Article][PubMed]
    [Google Scholar]
  28. Jing Y., Yang J., Wang Y., Li H., Chen Y., Hu Q., Shi G., Tang X., Yi J. 2006; Alteration of subcellular redox equilibrium and the consequent oxidative modification of nuclear factor kappaB are critical for anticancer cytotoxicity by emodin, a reactive oxygen species-producing agent. Free Radic Biol Med 40:2183–2197 [View Article][PubMed]
    [Google Scholar]
  29. Jones S. M., Dang T. T., Martinuzzi R. 2009; Use of quorum sensing antagonists to deter the formation of crystalline Proteus mirabilis biofilms. Int J Antimicrob Agents 34:360–364 [View Article][PubMed]
    [Google Scholar]
  30. Kim Y. M., Lee C. H., Kim H. G., Lee H. S. 2004; Anthraquinones isolated from Cassia tora (Leguminosae) seed show an antifungal property against phytopathogenic fungi. J Agric Food Chem 52:6096–6100 [View Article][PubMed]
    [Google Scholar]
  31. Kwak H. J., Park M. J., Park C. M., Moon S. I., Yoo D. H., Lee H. C., Lee S. H., Kim M. S., Lee H. W. et al. other authors 2006; Emodin inhibits vascular endothelial growth factor-A-induced angiogenesis by blocking receptor-2 (KDR/Flk-1) phosphorylation. Int J Cancer 118:2711–2720 [View Article][PubMed]
    [Google Scholar]
  32. Lewis K. 2007; Persister cells, dormancy and infectious disease. Nat Rev Microbiol 5:48–56 [View Article][PubMed]
    [Google Scholar]
  33. Lynch M. J., Swift S., Kirke D. F., Keevil C. W., Dodd C. E., Williams P. 2002; The regulation of biofilm development by quorum sensing in Aeromonas hydrophila. . Environ Microbiol 4:18–28 [View Article][PubMed]
    [Google Scholar]
  34. Ma Z., Otsuyama K., Liu S., Abroun S., Ishikawa H., Tsuyama N., Obata M., Li F. J., Zheng X. et al. other authors 2005; Baicalein, a component of Scutellaria radix from Huang-Lian-Jie-Du-Tang (HLJDT), leads to suppression of proliferation and induction of apoptosis in human myeloma cells. Blood 105:3312–3318 [View Article][PubMed]
    [Google Scholar]
  35. Ma R., Di L. Q., Xu H. Q. 2008; Optimization of extraction technology of free anthraquinones from Rheum. Chin Tradit Herb Drugs 39:858–860
    [Google Scholar]
  36. Manefield M., de Nys R., Kumar N., Read R., Givskov M., Steinberg P., Kjelleberg S. 1999; Evidence that halogenated furanones from Delisea pulchra inhibit acylated homoserine lactone (AHL)-mediated gene expression by displacing the AHL signal from its receptor protein. Microbiology 145:283–291 [View Article][PubMed]
    [Google Scholar]
  37. 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[PubMed]
    [Google Scholar]
  38. Meng E. C., Gschwend D. A., Blaney J. M., Kuntz I. D. 1993; Orientational sampling and rigid-body minimization in molecular docking. Proteins 17:266–278 [View Article][PubMed]
    [Google Scholar]
  39. Mittal R., Sharma S., Chhibber S., Harjai K. 2006; Contribution of quorum-sensing systems to virulence of Pseudomonas aeruginosa in an experimental pyelonephritis model. J Microbiol Immunol Infect 39:302–309[PubMed]
    [Google Scholar]
  40. Müh U., Hare B. J., Duerkop B. A., Schuster M., Hanzelka B. L., Heim R., Olson E. R., Greenberg E. P. 2006; A structurally unrelated mimic of a Pseudomonas aeruginosa acyl-homoserine lactone quorum-sensing signal. Proc Natl Acad Sci U S A 103:16948–16952 [View Article][PubMed]
    [Google Scholar]
  41. Muto A., Hori M., Sasaki Y., Saitoh A., Yasuda I., Maekawa T., Uchida T., Asakura K., Nakazato T. et al. other authors 2007; Emodin has a cytotoxic activity against human multiple myeloma as a Janus-activated kinase 2 inhibitor. Mol Cancer Ther 6:987–994 [View Article][PubMed]
    [Google Scholar]
  42. Parsek M. R., Greenberg E. P. 2000; Acyl-homoserine lactone quorum sensing in gram-negative bacteria: a signaling mechanism involved in associations with higher organisms. Proc Natl Acad Sci U S A 97:8789–8793 [View Article][PubMed]
    [Google Scholar]
  43. Passador L., Cook J. M., Gambello M. J., Rust L., Iglewski B. H. 1993; Expression of Pseudomonas aeruginosa virulence genes requires cell-to-cell communication. Science 260:1127–1130 [View Article][PubMed]
    [Google Scholar]
  44. Pettersen E. F., Goddard T. D., Huang C. C., Couch G. S., Greenblatt D. M., Meng E. C., Ferrin T. E. 2004; UCSF Chimera – a visualization system for exploratory research and analysis. J Comput Chem 25:1605–1612 [View Article][PubMed]
    [Google Scholar]
  45. Pompilio A., Catavitello C., Picciani C., Confalone P., Piccolomini R., Savini V., Fiscarelli E., D’Antonio D., Di Bonaventura G. 2010; Subinhibitory concentrations of moxifloxacin decrease adhesion and biofilm formation of Stenotrophomonas maltophilia from cystic fibrosis. J Med Microbiol 59:76–81 [View Article][PubMed]
    [Google Scholar]
  46. Rasmussen T. B., Givskov M. 2006; Quorum-sensing inhibitors as anti-pathogenic drugs. Int J Med Microbiol 296:149–161 [View Article][PubMed]
    [Google Scholar]
  47. Rasmussen T. B., Bjarnsholt T., Skindersoe M. E., Hentzer M., Kristoffersen P., Köte M., Nielsen J., Eberl L., Givskov M. 2005a; Screening for quorum-sensing inhibitors (QSI) by use of a novel genetic system, the QSI selector. J Bacteriol 187:1799–1814 [View Article][PubMed]
    [Google Scholar]
  48. 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. et al. other authors 2005b; Identity and effects of quorum-sensing inhibitors produced by Penicillium species. Microbiology 151:1325–1340 [View Article][PubMed]
    [Google Scholar]
  49. Rumbaugh K. P., Griswold J. A., Hamood A. N. 2000; The role of quorum sensing in the in vivo virulence of Pseudomonas aeruginosa. . Microbes Infect 2:1721–1731 [View Article][PubMed]
    [Google Scholar]
  50. Shih P. C., Huang C. T. 2002; Effects of quorum-sensing deficiency on Pseudomonas aeruginosa biofilm formation and antibiotic resistance. J Antimicrob Chemother 49:309–314 [View Article][PubMed]
    [Google Scholar]
  51. Stover C. K., Pham X. Q., Erwin A. L., Mizoguchi S. D., Warrener P., Hickey M. J., Brinkman F. S., Hufnagle W. O., Kowalik D. J. et al. other authors 2000; Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen. Nature 406:959–964 [View Article][PubMed]
    [Google Scholar]
  52. Su Y. T., Chang H. L., Shyue S. K., Hsu S. L. 2005; Emodin induces apoptosis in human lung adenocarcinoma cells through a reactive oxygen species-dependent mitochondrial signaling pathway. Biochem Pharmacol 70:229–241 [View Article][PubMed]
    [Google Scholar]
  53. Vannini A., Volpari C., Gargioli C., Muraglia E., Cortese R., De Francesco R., Neddermann P., Marco S. D. 2002; The crystal structure of the quorum sensing protein TraR bound to its autoinducer and target DNA. EMBO J 21:4393–4401 [View Article][PubMed]
    [Google Scholar]
  54. Vattem D. A., Mihalik K., Crixell S. H., McLean R. J. 2007; Dietary phytochemicals as quorum sensing inhibitors. Fitoterapia 78:302–310 [View Article][PubMed]
    [Google Scholar]
  55. Waters C. M., Lu W., Rabinowitz J. D., Bassler B. L. 2008; Quorum sensing controls biofilm formation in Vibrio cholerae through modulation of cyclic di-GMP levels and repression of vpsT. . J Bacteriol 190:2527–2536 [View Article][PubMed]
    [Google Scholar]
  56. Yan Q., Wu X. G., Wei H. L., Wang H. M., Zhang L. Q. 2009; Differential control of the PcoI/PcoR quorum-sensing system in Pseudomonas fluorescens 2P24 by sigma factor RpoS and the GacS/GacA two-component regulatory system. Microbiol Res 164:18–26 [View Article][PubMed]
    [Google Scholar]
  57. Yao Y., Martinez-Yamout M. A., Dickerson T. J., Brogan A. P., Wright P. E., Dyson H. J. 2006; Structure of the Escherichia coli quorum sensing protein SdiA: activation of the folding switch by acyl homoserine lactones. J Mol Biol 355:262–273 [View Article][PubMed]
    [Google Scholar]
  58. You J. L., Xue X. L., Cao L. X., Lu X., Wang J., Zhang L., Zhou S. N. 2007; Inhibition of Vibrio biofilm formation by a marine actinomycete strain A66. Appl Microbiol Biotechnol 76:1137–1144 [View Article][PubMed]
    [Google Scholar]
  59. Zeng Z. R., Qian L., Cao L. X., Tan H., Huang Y., Xue X., Shen Y., Zhou S. 2008; Virtual screening for novel quorum sensing inhibitors to eradicate biofilm formation of Pseudomonas aeruginosa. . Appl Microbiol Biotechnol 79:119–126 [View Article][PubMed]
    [Google Scholar]
  60. Zhu J., Winans S. C. 2001; The quorum-sensing transcriptional regulator TraR requires its cognate signaling ligand for protein folding, protease resistance, and dimerization. Proc Natl Acad Sci U S A 98:1507–1512 [View Article][PubMed]
    [Google Scholar]
  61. Zhu J., Beaber J. W., Moré M. I., Fuqua C., Eberhard A., Winans S. C. 1998; Analogs of the autoinducer 3-oxooctanoyl-homoserine lactone strongly inhibit activity of the TraR protein of Agrobacterium tumefaciens. . J Bacteriol 180:5398–5405[PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.024166-0
Loading
/content/journal/jmm/10.1099/jmm.0.024166-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error