1887

Abstract

The increasing incidence of associated disease, and the problems associated with its control, highlight the need for additional countermeasures. The attenuation of virulence through the blockade of bacterial cell-to-cell communication (quorum sensing) is one potential therapeutic target. Preliminary studies have shown that produces at least one potential signalling molecule. Through the molecule's ability to induce bioluminescence in a reporter strain, it has been shown to correspond to autoinducer 2 (AI-2). In keeping with this observation, a homologue of has been identified in the genome of . Adjacent to a potential transcriptional regulator and sensor kinase, and , have been located. RT-PCR has been used to confirm the genetic organization of the locus. While AI-2 production has not been blocked so far using antisense technology, AI-2 levels could be modulated by controlling expression of the putative transcriptional regulator . RolA, therefore, acts as a negative regulator of AI-2 production. Finally, it has been shown that the exogenous addition of AI-2 or 4-hydroxy-5-methyl-3(2) furanone has no discernible effect on the production of toxins by .

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2005-02-01
2024-03-28
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References

  1. Banu S., Ohtani K., Yaguchi H., Swe T., Cole S. T., Hayashi H., Shimizu T. 2000; Identification of novel VirR/VirS-regulated genes in Clostridium perfringens . Mol Microbiol 35:854–864 [CrossRef]
    [Google Scholar]
  2. Bassler B. L., Wright M., Showalter R. E., Silverman M. R. 1993; Intercellular signaling in Vibrio harveyi – sequence and function of genes regulating expression of luminescence. Mol Microbiol 9:773–786 [CrossRef]
    [Google Scholar]
  3. 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]
  4. Burgess N. A., Kirke D. F., Williams P., Winzer K., Hardie K. R., Meyers N. L., Aduse-Opoku J., Curtis M. A., Camara M. 2002; LuxS-dependent quorum sensing in Porphyromonas gingivalis modulates protease and haemagglutinin activities but is not essential for virulence. Microbiology 148:763–772
    [Google Scholar]
  5. 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]
  6. Chambers S. P., Prior S. E., Barstow D. A., Minton N. P. 1988; The pMTL nic- cloning vectors.I. Improved pUC polylinker regions to facilitate the use of sonicated DNA for nucleotide sequencing. Gene 68:139–149 [CrossRef]
    [Google Scholar]
  7. Day W. A., Maurelli A. T. 2001; Shigella flexneri LuxS quorum-sensing system modulates virB expression but is not essential for virulence. Infect Immun 69:15–23 [CrossRef]
    [Google Scholar]
  8. Desai R. P., Papoutsakis E. T. 1999; Antisense RNA strategies for metabolic engineering of Clostridium acetobutylicum . Appl Environ Microbiol 65:936–945
    [Google Scholar]
  9. Dupuy B., Sonenshein A. L. 1998; Regulated transcription of Clostridium difficile toxin genes. Mol Microbiol 27:107–120 [CrossRef]
    [Google Scholar]
  10. 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]
  11. Guzman L. M., Belin D., Carson M. J., Beckwith J. 1995; Tight regulation, modulation, and high-level expression by vectors containing the arabinose P-Bad promoter. J Bacteriol 177:4121–4130
    [Google Scholar]
  12. Kleerebezem M., Quadri L. E. N., Kuipers O. P., de Vos W. M. 1997; Quorum sensing by peptide pheromones and two-component signal-transduction systems in Gram-positive bacteria. Mol Microbiol 24:895–904 [CrossRef]
    [Google Scholar]
  13. Liyanage H., Kashket S., Young M., Kashket E. R. 2001; Clostridium beijerinckii and Clostridium difficile detoxify methylglyoxal by a novel mechanism involving glycerol dehydrogenase. Appl Environ Microbiol 67:2004–2010 [CrossRef]
    [Google Scholar]
  14. Lyon W. R., Madden J. C., Levin J. C., Stein J. L., Caparon M. G. 2001; Mutation of luxS affects growth and virulence factor expression in Streptococcus pyogenes . Mol Microbiol 42:145–157
    [Google Scholar]
  15. McDowell P., Affas Z., Reynolds C. & 8 other authors; 2001; Structure, activity and evolution of the group I thiolactone peptide quorum-sensing system of Staphylococcus aureus . Mol Microbiol 41:503–512 [CrossRef]
    [Google Scholar]
  16. Miller M. A., Hyland M., Ofner-Agostini M., Gourdeau M., Ishak M. 2002; Morbidity, mortality, and healthcare burden of nosocomial C.difficile -associated diarrhea in Canadian hospitals. Infect Control Hosp Epidemiol 23:137–140 [CrossRef]
    [Google Scholar]
  17. Minton N. P., Brehm J. K., Oultram J. D. & 8 other authors; 1990; Vector systems for the genetic analysis of Clostridium acetobutylicum . In Anaerobes in Human Medicine and Industry pp 187–206 Edited by Boriello P., Hardie J. Petersfield, UK: Wrightson Publishing;
    [Google Scholar]
  18. Mylonakis E., Ryan E. T., Calderwood S. B. 2001; C.difficile -associated diarrhea : a review. Arch Intern Med 161:525–533 [CrossRef]
    [Google Scholar]
  19. Novick R. P., Muir W. M. 1999; Virulence gene regulation by peptides in staphylococci and other Gram-positive bacteria. Curr Opin Microbiol 2:40–45 [CrossRef]
    [Google Scholar]
  20. Ohtani K., Hayashi H., Shimizu T. 2002; The luxS gene is involved in cell-cell signalling for toxin production in Clostridium perfringens . Mol Microbiol 44:171–179 [CrossRef]
    [Google Scholar]
  21. Perret S., Maamar H., Belaich J. P., Tardif C. 2004; Use of antisense RNA to modify the composition of cellulosomes produced by Clostridium cellulolyticum . Mol Microbiol 51:599–607 [CrossRef]
    [Google Scholar]
  22. Purdy D., O'Keeffe T. A. T., Elmore M., Herbert M., McLeod A., Bokori-Brown M., Ostrowski A., Minton N. P. 2002; Conjugative transfer of clostridial shuttle vectors from Escherichia coli to Clostridium difficile through circumvention of the restriction barrier. Mol Microbiol 46:439–452 [CrossRef]
    [Google Scholar]
  23. Riley T. V. 1998; C.difficile : a pathogen of the nineties. Eur J Clin Microbiol Infect Dis 17:137–141
    [Google Scholar]
  24. Sambrook J., Fritsch E. F., Maniatis T. 1989 Molecular Cloning: a Laboratory Manual , 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  25. Schneider R., Lockatell C. V., Johnson D., Belas R. 2002; Detection and mutation of a luxS -encoded autoinducer in Proteus mirabilis . Microbiology 148:773–782
    [Google Scholar]
  26. Shimizu T., Okabe A., Rood J. I. 1997; Regulation of toxin production in Clostridium perfringens . In The Clostridia: Molecular Biology and Pathogenesis . pp 451–470 Edited by Rood J. I., McClane B. A., Songer J. G., Titball R. W. London: Academic Press;
  27. Spencer R. C. 1998; Clinical impact and associated costs of C.difficile -associated disease. J Antimicrob Chemother 41:5–12 [CrossRef]
    [Google Scholar]
  28. Sperandio V., Mellies J. L., Nguyen W., Shin S., Kaper J. B. 1999; Quorum sensing controls expression of the type III secretion gene transcription and protein secretion in enterohemorrhagic and enteropathogenic Escherichia coli . Proc Natl Acad Sci U S A 96:15196–15201 [CrossRef]
    [Google Scholar]
  29. Sturme M. H. J., Kleerebezem M., Nakayama J., Akkermans A. D. L., Vaughan E. E., de Vos W. M. 2002; Cell to cell communication by autoinducing peptides in Gram-positive bacteria. Antonie van Leeuwenhoek 81:233–243 [CrossRef]
    [Google Scholar]
  30. Surette M. G., Bassler B. L. 1999; Regulation of autoinducer production in Salmonella typhimurium . Mol Microbiol 31:585–595 [CrossRef]
    [Google Scholar]
  31. Surette M. G., Miller M. B., Bassler B. L. 1999; Quorum sensing in Escherichia coli , Salmonella typhimurium and Vibrio harveyi : a new family of genes responsible for autoinducer production. Proc Natl Acad Sci U S A 96:1639–1644 [CrossRef]
    [Google Scholar]
  32. Swift S., Downie J. A., Whithead N., Barnard A. M. L., Salmond G. P. C., Williams P. 2001; Quorum sensing as a population density dependent determinant of bacterial physiology. Adv Microb Physiol 45:199–270
    [Google Scholar]
  33. Tummala S. B., Welker N. E., Papoutsakis E. T. 2002; Metabolic engineering of the acetone formation pathway of Clostridium acetobutylicum using antisense RNA.In Abstracts of Papers of the American Chemical Society. 224116–BIOT
  34. Wilcox M. H., Smyth E. T. M. 1998; Incidence and impact of C.difficile infection in the UK, 1993-1996. J Hosp Infect 39:181–187 [CrossRef]
    [Google Scholar]
  35. Wilcox M. H., Cunniffe J. G., Trundle C., Redpath C. 1996; Financial burden of hospital-acquired C.difficile infection. J Hosp Infect 34:23–30 [CrossRef]
    [Google Scholar]
  36. Williams P. 2002; Quorum sensing: an emerging target for antibacterial chemotherapy?. Expert Opin Ther Targets 6:257–274 [CrossRef]
    [Google Scholar]
  37. Williams P., Camara M., Hardman A. & 7 other authors; 2000; Quorum sensing and the population dependent control of virulence. Philos Trans R Soc Lond Ser B Biol Sci 355:667–680 [CrossRef]
    [Google Scholar]
  38. Winzer K., Hardie K. R., Williams P. 2002a; Bacterial cell-to-cell communication: sorry, can't talk now – gone to lunch!. Curr Opin Microbiol 5:216–222 [CrossRef]
    [Google Scholar]
  39. Winzer K., Sun Y. H., Green A., Delory M., Blackley D., Hardie K. R., Baldwin T. J., Tang C. M. 2002b; Role of Neisseria meningitidis luxS in cell-to-cell signaling and bacteremic infection. Infect Immun 70:2245–2248 [CrossRef]
    [Google Scholar]
  40. Winzer K., Hardie K. R., Burgess N. & 8 other authors; 2002c; LuxS: its role in central metabolism and the in vitro synthesis of 4-hydroxy-5-methyl-3( 2H )-furanone. Microbiology 148:909–922
    [Google Scholar]
  41. Winzer K., Hardie K. R., Williams P. 2003; LuxS and autoinducer-2: their contribution to quorum sensing and metabolism in bacteria. Adv Appl Microbiol 53:291–396
    [Google Scholar]
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