1887

Abstract

Enterohaemorrhagic (EHEC) colonizes and proliferates at the mucosal surface, inducing severe diarrhoea. Short-chain fatty acids (SCFAs) are abundant in the intestine owing to the metabolic activity of microflora, and are important for colonic health. We found that, although a high concentration of SCFAs inhibited the growth of EHEC, at low concentrations, the SCFAs markedly enhanced the expression of the virulence genes required for cell adherence and the induction of attaching and effacing (A/E) lesions. Of the SCFAs tested, butyrate markedly enhanced the expression of these virulence-associated genes, even at the low concentration of 1.25 mM, but acetate and propionate showed only a small effect at concentrations higher than 40 mM. Butyrate enhanced the promoter activity of the operon, which encodes a global regulator of the LEE genes, Ler. This enhancement was dependent on a regulator, PchA. Butyrate sensing was completely abrogated by the deletion of , the gene for the leucine-responsive regulatory protein, Lrp. Expression of a constitutively active mutant of Lrp enhanced the expression of the LEE genes in the absence of butyrate, and a response-defective Lrp derivative reduced the response to butyrate. Thus, upon entering the distal ileum, EHEC may respond to the higher butyrate level via Lrp by increasing its virulence expression, leading to efficient colonization of the target niche.

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2009-02-01
2024-12-14
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References

  1. Abe H., Miyahara A., Oshima T., Tashiro K., Ogura Y., Kuhara S., Ogasawara N., Hayashi T., Tobe T. 2008; Global regulation by horizontally transferred regulators establishes the pathogenicity of Escherichia coli . DNA Res 15:25–38
    [Google Scholar]
  2. Argenzio R. A., Southworth M., Stevens C. E. 1974; Sites of organic acid production and absorption in the equine gastrointestinal tract. Am J Physiol 226:1043–1050
    [Google Scholar]
  3. Brinkman A. B., Ettema T. J. G., de Vos W. M., van der Oost J. 2003; The Lrp family of transcriptional regulators. Mol Microbiol 48:287–294
    [Google Scholar]
  4. Chen S., Hao Z., Bieniek E., Calvo J. M. 2001; Modulation of Lrp action in Escherichia coli by leucine: effects on non-specific binding of Lrp to DNA. J Mol Biol 314:1067–1075
    [Google Scholar]
  5. Chong Y., Fitzhenry R., Heuschkel R., Torrente F., Frankel G., Phillips A. D. 2007; Human intestinal tissue tropism in Escherichia coli O157 : H7 – initial colonization of terminal ileum and Peyer's patches and minimal colonic adhesion ex vivo . Microbiology 153:794–802
    [Google Scholar]
  6. Cummings J. H., Macfarlane G. T. 1991; The control and consequences of bacterial fermentation in the human colon. J Appl Bacteriol 70:443–459
    [Google Scholar]
  7. Datsenko K. A., Wanner B. L. 2000; One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci U S A 97:6640–6645
    [Google Scholar]
  8. Hamer H. M., Jonkers D., Venema K., Vanhoutvin S., Troost F. J., Brummer R. J. 2008; Review article: the role of butyrate on colonic function. Aliment Pharmacol Ther 27:104–119
    [Google Scholar]
  9. Hayashi T., Makino K., Ohnishi M., Kurokawa K., Ishii K., Yokoyama K., Han C. G., Ohtsubo E., Nakayama K. other authors 2001; Complete genome sequence of enterohemorrhagic Escherichia coli O157 : H7 and genomic comparison with a laboratory strain K-12. DNA Res 8:11–22
    [Google Scholar]
  10. Iyoda S., Watanabe H. 2004; Positive effects of multiple pch genes on expression of the locus of enterocyte effacement genes and adherence of enterohaemorrhagic Escherichia coli O157 : H7 to HEp-2 cells. Microbiology 150:2357–2371
    [Google Scholar]
  11. Lawhon S. D., Maurer R., Suyemoto M., Altier C. 2002; Intestinal short-chain fatty acids alter Salmonella typhimurium invasion gene expression and virulence through BarA/SirA. Mol Microbiol 46:1451–1464
    [Google Scholar]
  12. Louis P., Scott K. P., Duncan S. H., Flint H. J. 2007; Understanding the effects of diet on bacterial metabolism in the large intestine. J Appl Microbiol 102:1197–1208
    [Google Scholar]
  13. Mellies J. L., Barron A. M. S., Carmona A. M. 2007; Enteropathogenic and enterohemorrhagic Escherichia coli virulence gene regulation. Infect Immun 75:4199–4210
    [Google Scholar]
  14. Miller J. H. 1972 Experiments in Molecular Genetics Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
  15. Nakanishi N., Abe H., Ogura Y., Hayashi T., Tashiro K., Kuhara S., Sugimoto N., Tobe T. 2006; ppGpp with DksA controls gene expression in the locus of enterocyte effacement (LEE) pathogenicity island of enterohaemorrhagic Escherichia coli through activation of two virulence regulatory genes. Mol Microbiol 61:194–205
    [Google Scholar]
  16. Nataro J. P., Kaper J. B. 1998; Diarrheagenic Escherichia coli . Clin Microbiol Rev 11:142–201
    [Google Scholar]
  17. Platko J. V., Calvo J. M. 1993; Mutations affecting the ability of Escherichia coli Lrp to bind DNA, activate transcription, or respond to leucine. J Bacteriol 175:1110–1117
    [Google Scholar]
  18. Tatsuno I., Kimura H., Okutani A., Kanamaru K., Abe H., Nagai S., Makino K., Shinagawa H., Yoshida M. other authors 2000; Isolation and characterization of mini-Tn5Km2 insertion mutants of enterohemorrhagic Escherichia coli O157 : H7 deficient in adherence to Caco-2 cells. Infect Immun 68:5943–5952
    [Google Scholar]
  19. Tobe T., Ando H., Ishikawa H., Abe H., Tashiro K., Hayashi T., Kuhara S., Sugimoto N. 2005; Dual regulatory pathways integrating the RcsC-RcsD-RcsB signalling system control enterohaemorrhagic Escherichia coli pathogenicity. Mol Microbiol 58:320–333
    [Google Scholar]
  20. Topping D. L., Clifton P. M. 2001; Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol Rev 81:1031–1064
    [Google Scholar]
  21. Van Deun K., Pasmans F., Van Immerseel F., Ducatelle R., Haesebrouck F. 2008; Butyrate protects Caco-2 cells from Campylobacter jejuni invasion and translocation. Br J Nutr 100:480–484
    [Google Scholar]
  22. Van Immerseel F., Boyen F., Gantois I., Timbermont L., Bohez L., Pasmans F., Haesebrouck F., Ducatelle R. 2005; Supplementation of coated butyric acid in the feed reduces colonization and shedding of Salmonella in poultry. Poult Sci 84:1851–1856
    [Google Scholar]
  23. Wong J. M., de Souza R., Kendall C. W., Emam A., Jenkins D. J. 2006; Colonic health: fermentation and short chain fatty acids. J Clin Gastroenterol 40:235–243
    [Google Scholar]
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