1887

Abstract

is an intestinal commensal that cannot synthesize porphyrins and only expresses a functional respiratory chain when provided with exogenous haematin. In the absence of haematin, reverts to fermentative metabolism and produces extracellular superoxide that can damage epithelial-cell DNA. The acute response of the colonic mucosa to haematin-starved was identified by gene array. was inoculated into murine colons using a surgical ligation model that preserved tissue architecture and homeostasis. The mucosa was exposed to haematin-starved and compared with a control consisting of the same strain grown with haematin. At 1 h post-inoculation, 6 mucosal genes were differentially regulated and this increased to 42 genes at 6 h. At 6 h, a highly significant biological interaction network was identified with functions that included nuclear factor-B (NF-B) signalling, apoptosis and cell-cycle regulation. Colon biopsies showed no histological abnormalities by haematoxylin and eosin staining. Immunohistochemical staining, however, detected NF-B activation in tissue macrophages using antibodies to the nuclear localization sequence for p65 and the F4/80 marker for murine macrophages. Similarly, haematin-starved strongly activated NF-B in murine macrophages . Furthermore, primary and transformed colonic epithelial cells activated the G/M checkpoint following exposure to haematin-starved . Modulation of this cell-cycle checkpoint was due to extracellular superoxide produced as a result of the respiratory block in haematin-starved . These results demonstrate that the uniquely dichotomous metabolism of can significantly modulate gene expression in the colonic mucosa for pathways associated with inflammation, apoptosis and cell-cycle regulation.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.47798-0
2008-10-01
2019-10-22
Loading full text...

Full text loading...

/deliver/fulltext/jmm/57/10/1193.html?itemId=/content/journal/jmm/10.1099/jmm.0.47798-0&mimeType=html&fmt=ahah

References

  1. Arakawa, H. ( 2004; ). Netrin-1 and its receptors in tumorigenesis. Nat Rev Cancer 4, 978–987.[CrossRef]
    [Google Scholar]
  2. Attene-Ramos, M. S., Wagner, E. D., Plewa, M. J. & Gaskins, H. R. ( 2006; ). Evidence that hydrogen sulfide is a genotoxic agent. Mol Cancer Res 4, 9–14.[CrossRef]
    [Google Scholar]
  3. Augenlicht, L. H., Mariadason, J. M., Wilson, A., Arango, D., Yang, W., Heerdt, B. G. & Velcich, A. ( 2002; ). Short chain fatty acids and colon cancer. J Nutr 132, 3804S–3808S.
    [Google Scholar]
  4. Austyn, J. M. & Gordon, S. ( 1981; ). F4/80, a monoclonal antibody directed specifically against the mouse macrophage. Eur J Immunol 11, 805–815.[CrossRef]
    [Google Scholar]
  5. Bäckhed, F., Ley, R. E., Sonnenburg, J. L., Peterson, D. A. & Gordon, J. I. ( 2005; ). Host–bacterial mutualism in the human intestine. Science 307, 1915–1920.[CrossRef]
    [Google Scholar]
  6. Balish, E. & Warner, T. ( 2002; ). Enterococcus faecalis induces inflammatory bowel disease in interleukin-10 knockout mice. Am J Pathol 160, 2253–2257.[CrossRef]
    [Google Scholar]
  7. Benno, Y., Suzuki, K., Suzuki, K., Narisawa, K., Bruce, W. R. & Mitsuoka, T. ( 1986; ). Comparison of the fecal microflora in rural Japanese and urban Canadians. Microbiol Immunol 30, 521–532.[CrossRef]
    [Google Scholar]
  8. Bouwmeester, T., Bauch, A., Ruffner, H., Angrand, P. O., Bergamini, G., Croughton, K., Cruciat, C., Eberhard, D., Gagneur, J. & other authors ( 2004; ). A physical and functional map of the human TNF-α/NF-κB signal transduction pathway. Nat Cell Biol 6, 97–105.[CrossRef]
    [Google Scholar]
  9. Bryan-Jones, D. G. & Whittenbury, R. ( 1969; ). Haematin-dependent oxidative phosphorylation in Streptococcus faecalis. J Gen Microbiol 58, 247–260.[CrossRef]
    [Google Scholar]
  10. Calvano, S. E., Xiao, W., Richards, D. R., Felciano, R. M., Baker, H. V., Cho, R. J., Chen, R. O., Brownstein, B. H., Cobb, J. P. & other authors ( 2005; ). A network-based analysis of systemic inflammation in humans. Nature 437, 1032–1037.[CrossRef]
    [Google Scholar]
  11. Chang, D. K., Goel, A., Ricciardiello, L., Lee, D. H., Chang, C. L., Carethers, J. M. & Boland, C. R. ( 2003; ). Effect of H2O2 on cell cycle and survival in DNA mismatch repair-deficient and -proficient cell lines. Cancer Lett 195, 243–251.[CrossRef]
    [Google Scholar]
  12. Chien, W., Kumagai, T., Miller, C. W., Desmond, J. C., Frank, J. M., Said, J. W. & Koeffler, H. P. ( 2004; ). Cyr61 suppresses growth of human endometrial cancer cells. J Biol Chem 279, 53087–53096.[CrossRef]
    [Google Scholar]
  13. Chu, F. F., Esworthy, R. S. & Doroshow, J. H. ( 2004; ). Role of Se-dependent glutathione peroxidases in gastrointestinal inflammation and cancer. Free Radic Biol Med 36, 1481–1495.[CrossRef]
    [Google Scholar]
  14. Debruyne, P. R., Bruyneel, E. A., Li, X., Zimber, A., Gespach, C. & Mareel, M. M. ( 2001; ). The role of bile acids in carcinogenesis. Mutat Res 480–481, 359–369.
    [Google Scholar]
  15. Dove, W. F., Clipson, L., Gould, K. A., Luongo, C., Marshall, D. J., Moser, A. R., Newton, M. A. & Jacoby, R. F. ( 1997; ). Intestinal neoplasia in the ApcMin mouse: independence from the microbial and natural killer (beige locus) status. Cancer Res 57, 812–814.
    [Google Scholar]
  16. Eckburg, P. B., Bik, E. M., Bernstein, C. N., Purdom, E., Dethlefsen, L., Sargent, M., Gill, S. R., Nelson, K. E. & Relman, D. A. ( 2005; ). Diversity of the human intestinal microbial flora. Science 308, 1635–1638.[CrossRef]
    [Google Scholar]
  17. Egeblad, M. & Werb, Z. ( 2002; ). New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2, 161–174.[CrossRef]
    [Google Scholar]
  18. Engle, S. J., Ormsby, I., Pawlowski, S., Boivin, G. P., Croft, J., Balish, E. & Doetschman, T. ( 2002; ). Elimination of colon cancer in germ-free transforming growth factor beta 1-deficient mice. Cancer Res 62, 6362–6366.
    [Google Scholar]
  19. Feng, D., Tu, Z., Wu, W. & Liang, C. ( 2003; ). Inhibiting the expression of DNA replication-initiation proteins induces apoptosis in human cancer cells. Cancer Res 63, 7356–7364.
    [Google Scholar]
  20. Fleiss, J. L. ( 1981; ). The comparison of proportions from several independent samples: ridit analysis. In Statistical Methods for Rates and Proportions, pp. 150–157. New York: John Wiley & Sons.
  21. Gentry-Weeks, C. R., Karkhoff-Schweizer, R., Pikis, A., Estay, M. & Keith, J. M. ( 1999; ). Survival of Enterococcus faecalis in mouse peritoneal macrophages. Infect Immun 67, 2160–2165.
    [Google Scholar]
  22. Gibson, G. R., Macfarlane, G. T. & Cummings, J. H. ( 1988; ). Occurrence of sulphate-reducing bacteria in human faeces and the relationship of dissimilatory sulphate reduction to methanogenesis in the large gut. J Appl Bacteriol 65, 103–111.[CrossRef]
    [Google Scholar]
  23. Gloire, G., Legrand-Poels, S. & Piette, J. ( 2006; ). NF-κB activation by reactive oxygen species: fifteen years later. Biochem Pharmacol 72, 1493–1505.[CrossRef]
    [Google Scholar]
  24. Gomez, D. E., Alonso, D. F., Yoshiji, H. & Thorgeirsson, U. P. ( 1997; ). Tissue inhibitors of metalloproteinases: structure, regulation and biological functions. Eur J Cell Biol 74, 111–122.
    [Google Scholar]
  25. Huycke, M. M. ( 2002; ). Physiology of enterococci. In Enterococci: Pathogenesis, Molecular Biology and Antibiotic Resistance, pp. 133–175. Edited by M. S. Gilmore. Washington, DC: American Society for Microbiology.
  26. Huycke, M. M. & Moore, D. R. ( 2002; ). In vivo production of hydroxyl radical by Enterococcus faecalis colonizing the intestinal tract using aromatic hydroxylation. Free Radic Biol Med 33, 818–826.[CrossRef]
    [Google Scholar]
  27. Huycke, M. M., Gilmore, M. S., Jett, B. D. & Booth, J. L. ( 1992; ). Transfer of pheromone-inducible plasmids between Enterococcus faecalis in the Syrian hamster gastrointestinal tract. J Infect Dis 166, 1188–1191.[CrossRef]
    [Google Scholar]
  28. Huycke, M. M., Joyce, W. & Wack, M. F. ( 1996; ). Augmented production of extracellular superoxide production by blood isolates of Enterococcus faecalis. J Infect Dis 173, 743–746.[CrossRef]
    [Google Scholar]
  29. Huycke, M. M., Moore, D., Shepard, L., Joyce, W., Wise, P., Kotake, Y. & Gilmore, M. S. ( 2001; ). Extracellular superoxide production by Enterococcus faecalis requires demethylmenaquinone and is attenuated by functional terminal quinol oxidases. Mol Microbiol 42, 729–740.
    [Google Scholar]
  30. Huycke, M. M., Abrams, V. & Moore, D. R. ( 2002; ). Enterococcus faecalis produces extracellular superoxide and hydrogen peroxide that damages colonic epithelial cell DNA. Carcinogenesis 23, 529–536.[CrossRef]
    [Google Scholar]
  31. Kado, S., Uchida, K., Funabashi, H., Iwata, S., Nagata, Y., Ando, M., Onoue, M., Matsuoka, Y., Ohwaki, M. & Morotomi, M. ( 2001; ). Intestinal microflora are necessary for development of spontaneous adenocarcinoma of the large intestine in T-cell receptor β chain and p53 double-knockout mice. Cancer Res 61, 2395–2398.
    [Google Scholar]
  32. Karin, M. & Greten, F. R. ( 2005; ). NF-κB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol 5, 749–759.[CrossRef]
    [Google Scholar]
  33. Khadaroo, R. G., Kapus, A., Powers, K. A., Cybulsky, M. I., Marshall, J. C. & Rotstein, O. D. ( 2003; ). Oxidative stress reprograms lipopolysaccharide signaling via Src kinase-dependent pathway in RAW 264.7 macrophage cell line. J Biol Chem 278, 47834–47841.[CrossRef]
    [Google Scholar]
  34. Kim, S. C., Tonkonogy, S. L., Albright, C. A., Tsang, J., Balish, E. J., Braun, J., Huycke, M. M. & Sartor, R. B. ( 2005; ). Variable phenotypes of enterocolitis in IL-10 deficient mice monoassociated with two different commensal bacteria. Gastroenterology 128, 891–906.[CrossRef]
    [Google Scholar]
  35. Klein, S., de Fougerolles, A. R., Blaikie, P., Khan, L., Pepe, A., Green, C. D., Koteliansky, V. & Giancotti, F. G. ( 2002; ). α5β1 integrin activates an NF-κB-dependent program of gene expression important for angiogenesis and inflammation. Mol Cell Biol 22, 5912–5922.[CrossRef]
    [Google Scholar]
  36. Kraehenbuhl, J.-P. & Neutra, M. R. ( 2000; ). Epithelial M cells: differentiation and function. Annu Rev Cell Dev Biol 16, 301–332.[CrossRef]
    [Google Scholar]
  37. Lin, M. T., Chang, C. C., Chen, S. T., Chang, H. L., Su, J. L., Chau, Y. P. & Kuo, M. L. ( 2004; ). Cyr61 expression confers resistance to apoptosis in breast cancer MCF-7 cells by a mechanism of NF-κB-dependent XIAP up-regulation. J Biol Chem 279, 24015–24023.[CrossRef]
    [Google Scholar]
  38. Lorimore, S. A. & Wright, E. G. ( 2003; ). Radiation-induced genomic instability and bystander effects: related inflammatory-type responses to radiation-induced stress and injury? A review. Int J Radiat Biol 79, 15–25.[CrossRef]
    [Google Scholar]
  39. Maggio-Price, L., Treuting, P., Zeng, W., Tsang, M., Bielefeldt-Ohmann, H. & Iritani, B. M. ( 2006; ). Helicobacter infection is required for inflammation and colon cancer in SMAD3-deficient mice. Cancer Res 66, 828–838.[CrossRef]
    [Google Scholar]
  40. Marnett, L. J. ( 2000; ). Oxyradicals and DNA damage. Carcinogenesis 21, 361–370.[CrossRef]
    [Google Scholar]
  41. Mazelin, L., Bernet, A., Bonod-Bidaud, C., Pays, L., Arnaud, S., Gespach, C., Bredesen, D. E., Scoazec, J. Y. & Mehlen, P. ( 2004; ). Netrin-1 controls colorectal tumorigenesis by regulating apoptosis. Nature 431, 80–84.[CrossRef]
    [Google Scholar]
  42. McGarr, S. E., Ridlon, J. M. & Hylemon, P. B. ( 2005; ). Diet, anaerobic bacterial metabolism, and colon cancer: a review of the literature. J Clin Gastroenterol 39, 98–109.
    [Google Scholar]
  43. Mendes, A. F., Caramona, M. M., Carvalho, A. P. & Lopes, M. C. ( 2003; ). Differential roles of hydrogen peroxide and superoxide in mediating IL-1-induced NF-κB activation and iNOS expression in bovine articular chondrocytes. J Cell Biochem 88, 783–793.[CrossRef]
    [Google Scholar]
  44. Mitra, S. & Abraham, E. ( 2006; ). Participation of superoxide in neutrophil activation and cytokine production. Biochim Biophys Acta 1762, 732–741.[CrossRef]
    [Google Scholar]
  45. Moore, W. E. C. & Moore, L. H. ( 1995; ). Intestinal floras of populations that have a high risk of colon cancer. Appl Environ Microbiol 61, 3202–3207.
    [Google Scholar]
  46. Nougayrede, J. P., Homburg, S., Taieb, F., Boury, M., Brzuszkiewicz, E., Gottschalk, G., Buchrieser, C., Hacker, J., Dobrindt, U. & Oswald, E. ( 2006; ). Escherichia coli induces DNA double-strand breaks in eukaryotic cells. Science 313, 848–851.[CrossRef]
    [Google Scholar]
  47. Ritchey, T. W. & Seeley, H. W. ( 1974; ). Cytochromes in Streptococcus faecalis var. zymogenes grown in a haematin-containing medium. J Gen Microbiol 85, 220–228.[CrossRef]
    [Google Scholar]
  48. Rowland, I. R. ( 1995; ). Toxicology of the colon: role of the intestinal microflora. In Human Colonic Bacteria: Role in Nutrition, Physiology, and Pathology, pp. 155–174. Edited by G. R. Gibson & G. T. Macfarlane. Boca Raton, FL: CRC Press.
  49. Su, T. T. ( 2006; ). Cellular responses to DNA damage: one signal, multiple choices. Annu Rev Genet 40, 187–208.[CrossRef]
    [Google Scholar]
  50. Taieb, F., Nougayrede, J. P., Watrin, C., Samba-Louaka, A. & Oswald, E. ( 2006; ). Escherichia coli cyclomodulin Cif induces G2 arrest of the host cell cycle without activation of the DNA-damage checkpoint-signalling pathway. Cell Microbiol 8, 1910–1921.[CrossRef]
    [Google Scholar]
  51. Vadigepalli, R., Chakravarthula, P., Zak, D. E., Schwaber, J. S. & Gonye, G. E. ( 2003; ). PAINT: a promoter analysis and interaction network generation tool for gene regulatory network identification. OMICS J Integr Biol 7, 235–252.[CrossRef]
    [Google Scholar]
  52. Waddell, S. J., Butcher, P. D. & Stoker, N. G. ( 2007; ). RNA profiling in host–pathogen interactions. Curr Opin Microbiol 10, 297–302.[CrossRef]
    [Google Scholar]
  53. Wang, X. & Huycke, M. M. ( 2007; ). Extracellular superoxide production by Enterococcus faecalis promotes chromosomal instability in mammalian cells. Gastroenterology 132, 551–561.[CrossRef]
    [Google Scholar]
  54. Wells, C. L., Jechorek, R. P. & Erlandsen, S. L. ( 1990; ). Evidence for the translocation of Enterococcus faecalis across the mouse intestinal tract. J Infect Dis 162, 82–90.[CrossRef]
    [Google Scholar]
  55. Whitehead, R. H., VanEeden, P. E., Noble, M. D., Ataliotis, P. & Jat, P. S. ( 1993; ). Establishment of conditionally immortalized epithelial cell lines from both colon and small intestine of adult H-2Kb -tsA58 transgenic mice. Proc Natl Acad Sci U S A 90, 587–591.[CrossRef]
    [Google Scholar]
  56. Xie, D., Miller, C. W., O’Kelly, J., Nakachi, K., Sakashita, A., Said, J. W., Gornbein, J. & Koeffler, H. P. ( 2001; ). Breast cancer. Cyr61 is overexpressed, estrogen-inducible, and associated with more advanced disease. J Biol Chem 276, 14187–14194.
    [Google Scholar]
  57. Yang, M., Sang, H., Rahman, A., Wu, D., Malik, A. B. & Ye, R. D. ( 2001; ). Gα 16 couples chemoattractant receptors to NF-κB activation. J Immunol 166, 6885–6892.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.47798-0
Loading
/content/journal/jmm/10.1099/jmm.0.47798-0
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