1887

Abstract

Quorum sensing (QS) communication systems are thought to afford bacteria with a mechanism to strategically cause disease. One example is , which infects immunocompromised individuals such as cystic fibrosis patients. The authors have previously documented that blockage of the QS systems not only attenuates but also renders biofilms highly susceptible to treatment with conventional antibiotics. Filamentous fungi produce a battery of secondary metabolites, some of which are already in clinical use as antimicrobial drugs. Fungi coexist with bacteria but lack active immune systems, so instead rely on chemical defence mechanisms. It was speculated that some of these secondary metabolites could interfere with bacterial QS communication. During a screening of 100 extracts from 50 species, 33 were found to produce QS inhibitory (QSI) compounds. In two cases, patulin and penicillic acid were identified as being biologically active QSI compounds. Their effect on QS-controlled gene expression in was verified by DNA microarray transcriptomics. Similar to previously investigated QSI compounds, patulin was found to enhance biofilm susceptibility to tobramycin treatment. has developed QS-dependent mechanisms that block development of the oxidative burst in PMN neutrophils. Accordingly, when the bacteria were treated with either patulin or penicillic acid, the neutrophils became activated. In a mouse pulmonary infection model, was more rapidly cleared from the mice that were treated with patulin compared with the placebo group.

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2005-05-01
2019-10-17
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References

  1. Anwar, H., Dasgupta, M. K. & Costerton, J. W. ( 1990; ). Testing the susceptibility of bacteria in biofilms to antibacterial agents. Antimicrob Agents Chemother 34, 2043–2046.[CrossRef]
    [Google Scholar]
  2. Bassoe, C. F., Li, N., Ragheb, K., Lawler, G., Sturgis, J. & Robinson, J. P. ( 2003; ). Investigations of phagosomes, mitochondria, and acidic granules in human neutrophils using fluorescent probes. Cytometry 51, 21–29.
    [Google Scholar]
  3. Beatson, S. A., Whitchurch, C. B., Semmler, A. B. & Mattick, J. S. ( 2002a; ). Quorum sensing is not required for twitching motility in Pseudomonas aeruginosa. J Bacteriol 184, 3598–3604.[CrossRef]
    [Google Scholar]
  4. Beatson, S. A., Whitchurch, C. B., Sargent, J. L., Levesque, R. C. & Mattick, J. S. ( 2002b; ). Differential regulation of twitching motility and elastase production by Vfr in Pseudomonas aeruginosa. J Bacteriol 184, 3605–3613.[CrossRef]
    [Google Scholar]
  5. Bjarnsholt, T., Jensen, P. O., Burmolle, M., Hentzer, M., Haagensen, J. A., Hougen, H. P., Calum, H., Madsen, K. G., Moser, C., Molin, S., Holby, N. & Givskov, M. ( 2005; ). Pseudomonas aeruginosa tolerance to tobramycin, hydrogen peroxide and polymorphonuclear leukocytes is quorum-sensing dependent. Microbiology 151, 373–383.[CrossRef]
    [Google Scholar]
  6. Camara, M., Williams, P. & Hardman, A. ( 2002; ). Controlling infection by tuning in and turning down the volume of bacterial small-talk. Lancet Infect Dis 2, 667–676.[CrossRef]
    [Google Scholar]
  7. Chhabra, S. R., Stead, P., Bainton, N. J., Salmond, G. P., Stewart, G. S., Williams, P. & Bycroft, B. W. ( 1993; ). Autoregulation of carbapenem biosynthesis in Erwinia carotovora by analogues of N-(3-oxohexanoyl)-l-homoserine lactone. J Antibiot 46, 441–454.[CrossRef]
    [Google Scholar]
  8. Chugani, S. A., Whiteley, M., Lee, K. M., D'Argenio, D., Manoil, C. & Greenberg, E. P. ( 2001; ). QscR, a modulator of quorum-sensing signal synthesis and virulence in Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 98, 2752–2757.[CrossRef]
    [Google Scholar]
  9. Clark, D. J. & Maaløe, O. ( 1967; ). DNA replication and the division cycle Escherichia coli. J Mol Biol 23, 99–112.[CrossRef]
    [Google Scholar]
  10. Costerton, J. W., Stewart, P. S. & Greenberg, E. P. ( 1999; ). Bacterial biofilms: a common cause of persistent infections. Science 284, 1318–1322.[CrossRef]
    [Google Scholar]
  11. Davies, D. G., Parsek, M. R., Pearson, J. P., Iglewski, B. H., Costerton, J. W. & Greenberg, E. P. ( 1998; ). The involvement of cell-to-cell signals in the development of a bacterial biofilm. Science 280, 295–298.[CrossRef]
    [Google Scholar]
  12. Dworjanyn, S. A. & Steinberg, P. ( 1999; ). Localisation and surface quantification of secondary metabolites in the red alga Delisea pulchra. Mar Biol 133, 727–736.[CrossRef]
    [Google Scholar]
  13. Finch, R. G., Pritchard, D. I., Bycroft, B. W., Williams, P. & Stewart, G. S. ( 1998; ). Quorum sensing: a novel target for anti-infective therapy. J Antimicrob Chemother 42, 569–571.[CrossRef]
    [Google Scholar]
  14. Frisvad, J. C. & Filtenborg, O. ( 1983; ). Classification of terverticillate penicillia based on profiles of mycotoxins and other secondary metabolites. Appl Environ Microbiol 46, 1301–1310.
    [Google Scholar]
  15. Frisvad, J. C., Smedsgaard, J., Larsen, T. O. & Samson, R. A. ( 2004; ). Mycotoxins, drugs and other extrolites produced by species in Penicillium subgenus Penicillium. Stud Mycol 49, 1–174.
    [Google Scholar]
  16. Fuqua, W. C., Winans, S. C. & Greenberg, E. P. ( 1994; ). Quorum sensing in bacteria: the LuxR-LuxI family of cell density-responsive transcriptional regulators. J Bacteriol 176, 269–275.
    [Google Scholar]
  17. 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.
    [Google Scholar]
  18. Habeck, M. ( 2003; ). Stop talking at the back. Drug Discov Today 8, 279–280.[CrossRef]
    [Google Scholar]
  19. Hayes, A. W. ( 1981; ). Mycotoxin Teratogenicity and Mutagenicity. New York: CRC Press.
  20. Hentzer, M. & Givskov, M. ( 2003; ). Pharmacological inhibition of quorum sensing for the treatment of chronic bacterial infections. J Clin Invest 112, 1300–1307.[CrossRef]
    [Google Scholar]
  21. Hentzer, M., Riedel, K., Rasmussen, T. B. & 9 other authors ( 2002; ). Inhibition of quorum sensing in Pseudomonas aeruginosa biofilm bacteria by a halogenated furanone compound. Microbiology 148, 87–102.
    [Google Scholar]
  22. Hentzer, M., Wu, H., Andersen, J. B. & 15 other authors ( 2003; ). Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. EMBO J 22, 3803–3815.[CrossRef]
    [Google Scholar]
  23. Hoiby, N. ( 1974; ). Epidemiological investigations of the respiratory tract bacteriology in patients with cystic fibrosis. Acta Pathol Microbiol Scand [B] Microbiol Immunol 82, 541–550.
    [Google Scholar]
  24. Hoiby, N. ( 2000; ). Prospects for the prevention and control of pseudomonal infection in children with cystic fibrosis. Paediatr Drugs 2, 451–463.[CrossRef]
    [Google Scholar]
  25. Hoiby, N. & Koch, C. ( 2000; ). Maintenance treatment of chronic Pseudomonas aeruginosa infection in cystic fibrosis. Thorax 55, 349–350.[CrossRef]
    [Google Scholar]
  26. Huber, B., Riedel, K., Hentzer, M., Heydorn, A., Gotschlich, A., Givskov, M., Molin, S. & Eberl, L. ( 2001; ). The cep quorum-sensing system of Burkholderia cepacia H111 controls biofilm formation and swarming motility. Microbiology 147, 2517–2528.
    [Google Scholar]
  27. Juhas, M., Wiehlmann, L., Huber, B. & 8 other authors ( 2004; ). Global regulation of quorum sensing and virulence by VqsR in Pseudomonas aeruginosa. Microbiology 150, 831–841.[CrossRef]
    [Google Scholar]
  28. Kjelleberg, S., Steinberg, P., Givskov, M., Gram, L., Manefield, M. & de Nys, R. ( 1997; ). Do marine natural products interfere with prokaryotic AHL regulatory systems? Aquat Microb Ecol 13, 85–93.[CrossRef]
    [Google Scholar]
  29. Ledgham, F., Ventre, I., Soscia, C., Foglino, M., Sturgis, J. N. & Lazdunski, A. ( 2003; ). Interactions of the quorum sensing regulator QscR: interaction with itself and the other regulators of Pseudomonas aeruginosa LasR and RhlR. Mol Microbiol 48, 199–210.[CrossRef]
    [Google Scholar]
  30. Manefield, M., Harris, L., Rice, S. A., de Nys, R. & Kjelleberg, S. ( 2000; ). Inhibition of luminescence and virulence in the black tiger prawn (Penaeus monodon) pathogen Vibrio harveyi by intercellular signal antagonists. Appl Environ Microbiol 66, 2079–2084.[CrossRef]
    [Google Scholar]
  31. 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]
  32. Maximilien, R., de Nys, R., Holmstrom, C., Gram, L., Givskov, M., Kjelleberg, S. & Steinberg, P. ( 1998; ). Chemical mediation of bacterial surface colonisation by secondary metabolites from the red alga Delisea pulchra. Aquat Microb Ecol 15, 233–246.[CrossRef]
    [Google Scholar]
  33. Moser, C., Johansen, H. K., Song, Z., Hougen, H. P., Rygaard, J. & Hoiby, N. ( 1997; ). Chronic Pseudomonas aeruginosa lung infection is more severe in Th2 responding BALB/c mice compared to Th1 responding C3H/HeN mice. APMIS 105, 838–842.[CrossRef]
    [Google Scholar]
  34. Moser, C., Hougen, H. P., Song, Z., Rygaard, J., Kharazmi, A. & Hoiby, N. ( 1999; ). Early immune response in susceptible and resistant mice strains with chronic Pseudomonas aeruginosa lung infection determines the type of T-helper cell response. APMIS 107, 1093–1100.[CrossRef]
    [Google Scholar]
  35. Moser, C., Kjaergaard, S., Pressler, T., Kharazmi, A., Koch, C. & Hoiby, N. ( 2000; ). The immune response to chronic Pseudomonas aeruginosa lung infection in cystic fibrosis patients is predominantly of the Th2 type. APMIS 108, 329–335.[CrossRef]
    [Google Scholar]
  36. Nouwens, A. S., Beatson, S. A., Whitchurch, C. B., Walsh, B. J., Schweizer, H. P., Mattick, J. S. & Cordwell, S. J. ( 2003; ). Proteome analysis of extracellular proteins regulated by the las and rhl quorum sensing systems in Pseudomonas aeruginosa PAO1. Microbiology 149, 1311–1322.[CrossRef]
    [Google Scholar]
  37. Olsen, J. A., Severinsen, R., Rasmussen, T. B., Hentzer, M., Givskov, M. & Nielsen, J. ( 2002; ). Synthesis of new 3- and 4-substituted analogues of acyl homoserine lactone quorum sensing autoinducers. Bioorg Med Chem Lett 12, 325–328.[CrossRef]
    [Google Scholar]
  38. Passador, L., Tucker, K. D., Guertin, K. R., Journet, M. P., Kende, A. S. & Iglewski, B. H. ( 1996; ). Functional analysis of the Pseudomonas aeruginosa autoinducer PAI. J Bacteriol 178, 5995–6000.
    [Google Scholar]
  39. Pedersen, S. S., Shand, G. H., Hansen, B. L. & Hansen, G. N. ( 1990; ). Induction of experimental chronic Pseudomonas aeruginosa lung infection with P. aeruginosa entrapped in alginate microspheres. APMIS 98, 203–211.[CrossRef]
    [Google Scholar]
  40. Pritt, J. I. ( 1979; ). The Genus Penicillium and its Teleomorphic States Eupenicillium and Taleromyces. London: Academic Press.
  41. Rasmussen, T. B., Manefield, M., Andersen, J. B., Eberl, L., Anthoni, U., Christophersen, C., Steinberg, P., Kjelleberg, S. & Givskov, M. ( 2000; ). How Delisea pulchra furanones affect quorum sensing and swarming motility in Serratia liquefaciens MG1. Microbiology 146, 3237–3244.
    [Google Scholar]
  42. Rasmussen, T. B., Bjarnsholt, T., Skindersoe, M. E., Hentzer, M., Kristoffersen, P., Köte, M., Nielsen, J., Eberl, L. & Givskov, M. ( 2005; ). Screening for quorum sensing inhibitors using a novel genetic system – the QSI selector. J Bacteriol 187, 1799–1814.[CrossRef]
    [Google Scholar]
  43. Reverchon, S., Chantegrel, B., Deshayes, C., Doutheau, A. & Cotte-Pattat, N. ( 2002; ). New synthetic analogues of N-acyl homoserine lactones as agonists or antagonists of transcriptional regulators involved in bacterial quorum sensing. Bioorg Med Chem Lett 12, 1153–1157.[CrossRef]
    [Google Scholar]
  44. Salmond, G. P., Bycroft, B. W., Stewart, G. S. & Williams, P. ( 1995; ). The bacterial ‘enigma’: cracking the code of cell-cell communication. Mol Microbiol 16, 615–624.[CrossRef]
    [Google Scholar]
  45. Schaefer, A. L., Hanzelka, B. L., Eberhard, A. & Greenberg, E. P. ( 1996; ). Quorum sensing in Vibrio fischeri: probing autoinducer-LuxR interactions with autoinducer analogs. J Bacteriol 178, 2897–2901.
    [Google Scholar]
  46. Schuster, M., Lostroh, C. P., Ogi, T. & Greenberg, E. P. ( 2003; ). Identification, timing, and signal specificity of Pseudomonas aeruginosa quorum-controlled genes: a transcriptome analysis. J Bacteriol 185, 2066–2079.[CrossRef]
    [Google Scholar]
  47. Smedsgaard, J. ( 1997; ). Micro-scale extraction procedure for standardized screening of fungal metabolite production in cultures. J Chromatogr A 760, 264–270.[CrossRef]
    [Google Scholar]
  48. Smith, R. S. & Iglewski, B. H. ( 2003; ). Pseudomonas aeruginosa quorum sensing as a potential antimicrobial target. J Clin Invest 112, 1460–1465.[CrossRef]
    [Google Scholar]
  49. Smith, K. M., Bu, Y. & Suga, H. ( 2003a; ). Induction and inhibition of Pseudomonas aeruginosa quorum sensing by synthetic autoinducer analogs. Chem Biol 10, 81–89.[CrossRef]
    [Google Scholar]
  50. Smith, K. M., Bu, Y. & Suga, H. ( 2003b; ). Library screening for synthetic agonists and antagonists of a Pseudomonas aeruginosa autoinducer. Chem Biol 10, 563–571.[CrossRef]
    [Google Scholar]
  51. Steinberg, P. D., Schneider, R. & Kjelleberg, S. ( 1997; ). Chemical defences of seaweeds against microbial colonization. Biodegradation 8, 211–220.[CrossRef]
    [Google Scholar]
  52. Van Delden, C. & Iglewski, B. H. ( 1998; ). Cell-to-cell signalling and Pseudomonas aeruginosa infections. Emerg Infect Dis 4, 551–560.[CrossRef]
    [Google Scholar]
  53. Wagner, V. E., Bushnell, D., Passador, L., Brooks, A. I. & Iglewski, B. H. ( 2003; ). Microarray analysis of Pseudomonas aeruginosa quorum-sensing regulons: effects of growth phase and environment. J Bacteriol 185, 2080–2095.[CrossRef]
    [Google Scholar]
  54. Whiteley, M., Lee, K. M. & Greenberg, E. P. ( 1999; ). Identification of genes controlled by quorum sensing in Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 96, 13904–13909.[CrossRef]
    [Google Scholar]
  55. Wilderman, P. J., Vasil, A. I., Johnson, Z., Wilson, M. J., Cunliffe, H. E., Lamont, I. L. & Vasil, M. L. ( 2001; ). Characterization of an endoprotease (PrpL) encoded by a PvdS-regulated gene in Pseudomonas aeruginosa. Infect Immun 69, 5385–5394.[CrossRef]
    [Google Scholar]
  56. Wu, H., Song, Z., Hentzer, M., Andersen, J. B., Molin, S., Givskov, M. & Hoiby, N. ( 2004; ). Synthetic furanones inhibit quorum-sensing and enhance bacterial clearance in Pseudomonas aeruginosa lung infection in mice. J Antimicrob Chemother 53, 1054–1061.[CrossRef]
    [Google Scholar]
  57. Zhu, J., Beaber, J. W., More, M. I., Fuqua, C., Eberhard, A. & Winans, S. C. ( 1998; ). Analogues of the autoinducer 3-oxooctanoyl-homoserine lactone strongly inhibit activity of the TraR protein of Agrobacterium tumefaciens. J Bacteriol 180, 5398–5405.
    [Google Scholar]
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