Current Infectious Disease Reports

, Volume 10, Issue 2, pp 99–104 | Cite as

Enterotoxigenic Bacteroides fragilis

  • John Holton


Bacteroides fragilis is a minor component of the microbial flora of the intestine but the most frequent disease-causing anaerobe. Virulence characteristics are its capsule, which induces abscess formation, and the production of fragilysin, a Zn-metalloprotease. This toxin’s action is to hydrolyze the extracellular domain of E-cadherin, the effect of which is to disrupt intercellular adhesion and thus increase permeability of the epithelium, causing intracellular redistribution of actin with morphologic changes to the cells and release of β-catenin, which translocates to the nucleus and ultimately increases cellular proliferation. Clinically, enterotoxigenic B. fragilis is linked to secretory diarrhea, particularly in children. Preliminary evidence suggests that enterotoxigenic B. fragilis may also be linked to inflammatory bowel disease and colon cancer.


Intestinal Epithelial Cell Transepithelial Electrical Resistance Basolateral Surface Human Intestinal Epithelial Cell Bacteroides Fragilis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Kuwahara T, Yamashite A, Hirakawa H, et al.: Genomic analysis of Bacteroides fragilis reveals extensive DNA inversions regulating cell surface adaptation. Proc Nat Acad Sci USA 2004, 101:14919–14924.PubMedCrossRefGoogle Scholar
  2. 2.
    Cerdeño-Tárraga AM, Patrick S, Crossman LC, et al.: Extensive DNA inversions in the B. fragilis genome control variable gene expression. Science 2005, 307:1463–1465.PubMedCrossRefGoogle Scholar
  3. 3.
    Podglajen I, Breuil J, Casin I, Collatz E: Genotypic identification of two groups within the species Bacteroides fragilis by ribotyping and by analysis of PCR-generated fragment patterns and insertion sequence content. J Bacteriol 1995, 177:5270–5275.PubMedGoogle Scholar
  4. 4.
    Gutacker M, Valsangiacomo C, Piffaretti JC: Identification of two genetic groups in Bacteroides fragilis by multi locus enzyme electrophoresis: distribution of antibiotic resistance (CfiA, CepA) and enterotoxin (btf) encoding genes. Microbiology 2000, 146:1241–1254.PubMedGoogle Scholar
  5. 5.
    Moncrief JC, Duncan AJ, Wright RL et al.: Molecular characterization of the fragilysin pathogenicity islet of enterotoxigenic Bacteroides fragilis. Infect Immun 1998, 66:1735–1739.PubMedGoogle Scholar
  6. 6.
    Franco AA, Cheng RK, Chung GT, et al.: Molecular evolution of the pathogenicity island of enterotoxigenic Bacteroides fragilis strains. J Bacteriol 1999, 181:6623–6633.PubMedGoogle Scholar
  7. 7.
    Buckwold SL, Shoemaker NB, Sears CL, Franco AA: Identification and characterisation of conjugative transposons CTn86 and CTn9343 in Bacteroides fragilis strains. App Environ Microbiol 2007, 73:53–63.CrossRefGoogle Scholar
  8. 8.
    Kato N, Liu CX, Kato H, et al.: A new subtype of the metalloprotease toxin gene and the incidence of the three subtypes among Bacteroides fragilis isolates in Japan. FEMS Microbiol Lett 2000, 182:171–176.PubMedCrossRefGoogle Scholar
  9. 9.
    van Tassell RL, Lyerly DM, Wilkins TD: Purification and characterisation of an enterotoxin from Bacteroides fragilis. Infect Immun 1992, 60:1343–1350.PubMedGoogle Scholar
  10. 10.
    Franco AA, Buckwold SL, Shin JW, et al.: Mutation of the zinc binding metalloprotease motif affects Bacteroides fragilis toxin activity but does not affect propeptide processing. Infect Immun 2005, 73:5273–5277.PubMedCrossRefGoogle Scholar
  11. 11.
    Sears CL, Buckwald SL, Shin JW, Franco AA: The C-terminal region of Bacteroides fragilis toxin is essential to its biological activity. Infect Immun 2006, 74:5595–5601.PubMedCrossRefGoogle Scholar
  12. 12.
    Franco AA, Mundy LM, Trucksis M, et al.: Cloning and characterization of the Bacteroides fragilis metalloprotease toxin gene. Infect Immun 1997, 65:1007–1013.PubMedGoogle Scholar
  13. 13.
    Moncrief JS, Obiso RJ, Barroso LA, et al.: The enterotoxin of Bacteroides fragilis is a metalloprotease. Infect Immun 1995, 63:175–181.PubMedGoogle Scholar
  14. 14.
    Weikel CS, Grieco FD, Reuben J, et al.: Human colonic epithelial cells HT29/C1 treated with crude Bacteroides fragilis enterotoxin dramatically alter their morphology. Infect Immun 1992, 60:321–327.PubMedGoogle Scholar
  15. 15.
    Obiso RJ, Lyerly DM, van Tassell RL, Wilkins TD: Proteolytic activity of the Bacteroides fragilis enterotoxin causes fluid secretion and intestinal damage in vivo. Infect Immun 1995, 63:3820–3826.PubMedGoogle Scholar
  16. 16.
    Donelli G, Fabbri A, Fiorentini C: Bacteroides fragilis enterotoxin induces cytoskeletal changes and surface blebbing in HT-29 cells. Infect Immun 1996, 64:113–119.PubMedGoogle Scholar
  17. 17.
    Koshy SS, Montrose MH, Sears CL: Human intestinal epithelial cells swell and demonstrate actin re-arrangement in response to the metalloprotease toxin of Bacteroides fragilis. Infect Immun 1996, 64:5022–5028.PubMedGoogle Scholar
  18. 18.
    Saidi RF, Jaeger K, Montrose MH, et al.: Bacteroides fragilis toxin re-arranges the actin cytoskeleton of HT-29/C1 cells without direct proteolysis of actin or decrease in F-actin. Cell Motil Cytoskeleton 1997, 37:159–165.PubMedCrossRefGoogle Scholar
  19. 19.
    Obiso RJ, Azghani AO, Wilkins TD: The Bacteroides fragilis toxin fragilysin disrupts the paracellular barrier of epithelial cells. Infect Immun 1977, 65:1431–1439.Google Scholar
  20. 20.
    Chambers FG, Koshy SS, Saidi RF, et al.: Bacteroides fragilis toxin exhibits polar activity on monolayers of human intestinal epithelial cells (T84 cells) in vitro. Infect Immun 1997, 65:3561–3570.PubMedGoogle Scholar
  21. 21.
    Riegler M, Lotz M, Sears CL, et al.: Bacteroides fragilis toxin 2 damages human colonic mucosa in vitro. Gut 1999, 44:504–510.PubMedCrossRefGoogle Scholar
  22. 22.
    Wu S, Shin J, Zhang G, et al.: The Bacteroides fragilis toxin binds to a specific intestinal epithelial cell receptor. Infect Immun 2006, 74:5382–5390.PubMedCrossRefGoogle Scholar
  23. 23.
    Wu S, Lim KC, Huang J, et al.: Bacteroides fragilis enterotoxin cleaves the zonula adherens protein, E-cadherin. Proc Natl Acad Sci USA 1998, 95:14979–14984.PubMedCrossRefGoogle Scholar
  24. 24.
    Wu S, Rhee KJ, Zhang M, et al.: Bacteroides fragilis toxin stimulates intestinal epithelial cell shedding and gamma-secretase-dependent E-cadherin cleavage. J Cell Science 2007, 120:1944–1952.PubMedCrossRefGoogle Scholar
  25. 25.
    Wu S, Morin PJ, Maouyo D, Sears CL: Bacteroides fragilis enterotoxin induces c-myc expression and cellular proliferation. Gastroenterology 2003, 124:392–400.PubMedCrossRefGoogle Scholar
  26. 26.
    Sanfilippo L, Li CK, Seth R, et al.: Bacteroides fragilis enterotoxin induces the expression of IL-8 and transforming growth factor beta (TGF-beta) by human colonic epithelial cells. Clin Exp Immunol 2000, 119:456–463.PubMedCrossRefGoogle Scholar
  27. 27.
    Kim JM, Oh YK, Kim YJ, Cho YJ: Polarized secretion of CXC chemokines by human intestinal epithelial cells in response to Bacteroides fragilis enterotoxin: NFkappaB plays a major role in the regulation of IL-8 expression. Clin Exp Immunol 2001, 123:421–427.PubMedCrossRefGoogle Scholar
  28. 28.
    Kim JM, Cho SJ, Oh YK, et al.: Nuclear factor kappa B activation pathway in intestinal epithelial cells is a major regulator of chemokine gene expression and neutrophil migration induced by Bacteroides fragilis enterotoxin. Clin Exp Immunol 2002, 130:59–66.PubMedCrossRefGoogle Scholar
  29. 29.
    Wu S, Powell J, Mathioudakis N, et al.: Bacteroides fragilis enterotoxin induces intestinal epithelial cell secretion of interleukin 8 through mitogen activated protein kinases and a tyrosine kinase regulated nuclear factor kappa B pathway. Infect Immun 2004, 72:5832–5839.PubMedCrossRefGoogle Scholar
  30. 30.
    Kim JM, Jung HY, Lee JY, et al.: Mitogen activated protein kinase and activator protein-1 dependent signals are essential for Bacteroides fragilis enterotoxin induced enteritis. Eur J Immunol 2005, 35:2648–2657.PubMedCrossRefGoogle Scholar
  31. 31.
    Myers LL, Firehammer BD, Shoop DS, Border MM: Bacteroides fragilis: a possible cause of acute diarrhoeal disease in newborn lambs. Infect Immun 1984, 44:241–244.PubMedGoogle Scholar
  32. 32.
    Myers LL, Shoop DS, Stackhouse LL, et al.: Isolation of enterotoxigenic Bacteroides fragilis from humans with diarrhoea. J Clin Micro 1987, 25:2330–2333.Google Scholar
  33. 33.
    Shoop DS, Meyers LL, LeFever JB: Enumeration of enterotoxigenic Bacteroides fragilis in municipal sewage. App Env Microbiol 1990, 56:2243–2244.Google Scholar
  34. 34.
    Sack RB, Meyers LL, Almeido-Hill J, et al.: Enterotoxigenic Bacteroides fragilis: epidemiological studies of its role as a human diarrhoeal pathogen. J Diarrhoeal Dis Res 1992, 10:4–9.PubMedGoogle Scholar
  35. 35.
    Sack RB, Albert MJ, Alam K, et al.: Isolation of enterotoxigenic Bacteroides fragilis from Babgladeshi children with diarrhoea: a case controlled study. J Clin Micro 1994, 32:960–963.Google Scholar
  36. 36.
    San Joaquin VH, Griffis JC, Lee C, Dears CL: Association of Bacteroides fragilis with childhood diarrhoea. Scand J Infect Dis 1995, 27:211–215.PubMedCrossRefGoogle Scholar
  37. 37.
    Bressane MA, Durigon LE, Avila-Campos MJ: Prevalence of the Bacteroides fragilis group and enterotoxigenic Bacteroides fragilis in immunodeficient children. Anaerobe 2001, 7:277–281.CrossRefGoogle Scholar
  38. 38.
    Pantosi A, Menozzi MG, Frate A, et al.: Detection of enterotoxigenic Bacteroides fragilis and its toxin in stool samples from adults and children in Italy. Clin Infect Dis 1997, 24:12–16.Google Scholar
  39. 39.
    Zhang G, Svenungsson B, Karnell A, Weintraub A: Prevalence of enterotoxigenic Bacteroides fragilis in adult patients with diarrhoea and healthy controls. Clin Infect Dis 1999, 29:590–594.PubMedCrossRefGoogle Scholar
  40. 40.
    Scotto d’Abusco AS, Del Grosso M, Censini S, et al.: The alleles of the bft gene are distributed differently among enterotoxigenic Bacteroides fragilis strains from human sources and can be present in double copies. J Clin Microbiol 2000, 38:607–612.PubMedGoogle Scholar
  41. 41.
    Toprak UN, Rajendram D, Yagci A, et al.: The distribution of the bft alleles among enterotoxigenic Bacteroides fragilis strains from stool specimens and extraintestinal sites. Anaerobe 2006, 12:71–74.CrossRefGoogle Scholar
  42. 42.
    Avila-Campos MJ, Liu C, Song Y, et al.: Determination of bft gene subtypes in Bacteroides fragilis clinical isolates. J Clin Microbiol 2007, 45:1336–1338.PubMedCrossRefGoogle Scholar
  43. 43.
    Cohen SH, Shetab R, Tang-Feldman YJ, et al.: Prevalence of enterotoxigenic Bacteroides fragilis in hospital acquired diarrhoea. Diagn Microbiol Infect Dis 2006, 55:251–254.PubMedCrossRefGoogle Scholar
  44. 44.
    Toptak NU, Yagci A, Gulluoglu BM, et al.: A possible role of Bacteroides fragilis in the aetiology of colorectal cancer. Clin Microbiol Infect 2006, 12:782–786.Google Scholar
  45. 45.
    Prindiville TP, Sheikh RA, Cohen SH, et al.: Bacteroides fragilis enterotoxin gene sequence in patients with inflammatory bowel disease. Emerg Infect Dis 2000, 6:171–174.PubMedGoogle Scholar
  46. 46.
    Basset C, Holton J, Bazeos A, et al.: Are Helicobacter species and enterotoxigenic Bacteroides fragilis involved in inflammatory bowel disease? Dig Dis Sci 2004, 49:1425–1432.PubMedCrossRefGoogle Scholar
  47. 47.
    Vines RR, Perdue SS, Moncrief JS, et al.: Fragilysin, the enterotoxin from Bacteroides fragilis enhances the serum antibody response to antigens co-administered by the intranasal route. Vaccine 2000, 19:655–660.PubMedCrossRefGoogle Scholar
  48. 48.
    Rabizadeh S, Rhee KJ, Wu S, et al.: Enterotoxigenic bacteroides fragilis: a potential instigator of colitis. Inflamm Bowel Dis 2007, 13:1475–1483.PubMedCrossRefGoogle Scholar
  49. 49.
    Kato N, Kato H, Watanabe K, Ueno K: Association of enterotoxigenic Bacteroides fragilis with bacteraemia. Clin Infect Dis 1996, 23(Suppl 1):S83–S86.PubMedGoogle Scholar
  50. 50.
    Foulon I, Pierard D, Muyldermans G. et al.: Prevalence of fragilysin gene in Bacteroides fragilis isolates from blood and other extraintestinal samples. J Clin Microbiol 2003, 41:4428–4430.PubMedCrossRefGoogle Scholar

Copyright information

© Current Medicine Group LLC 2008

Authors and Affiliations

  1. 1.Centre for Infectious Diseases and International Health, Windeyer Institute of Medical SciencesUniversity College LondonLondonUK

Personalised recommendations