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.

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2008-10-01
2020-04-10
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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- κ B 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 480:481359–369
    [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;
    [Google Scholar]
  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- κ B 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 Gilmore M. S. Washington, DC: American Society for Microbiology;
    [Google Scholar]
  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- κ B: 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; α 5 β 1 integrin activates an NF- κ B-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- κ B-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- κ B 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 Gibson G. R., Macfarlane G. T. Boca Raton, FL: CRC Press;
    [Google Scholar]
  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; G α 16 couples chemoattractant receptors to NF- κ B activation. J Immunol 166:6885–6892 [CrossRef]
    [Google Scholar]
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