Enterotoxigenic Bacteroides Fragilis: a Rogue Among Symbiotes

Overview

Journal Clin Microbiol Rev

Publisher American Society for Microbiology

Specialty Microbiology

Date 2009 Apr 16

PMID 19366918

Citations 186

Authors

Cynthia L Sears

Affiliations

Soon will be listed here.

Abstract

Enterotoxigenic Bacteroides fragilis (ETBF) strains are strains of B. fragilis that secrete a 20-kDa heat-labile zinc-dependent metalloprotease toxin termed the B. fragilis toxin (BFT). BFT is the only recognized virulence factor specific for ETBF. ETBF strains are associated with inflammatory diarrheal disease in children older than 1 year of age and in adults; limited data suggest an association of ETBF colonization with inflammatory bowel disease flare-ups and colorectal cancer. ETBF secretes one of three highly related BFT isoforms. The relationship between BFT isoform and disease expression is unknown. Although the mechanism of action of BFT is incompletely understood, available data suggest that BFT binds to a specific intestinal epithelial cell receptor, stimulating intestinal cell signal transduction pathways that result in cell morphology changes, cleavage of E-cadherin, reduced colonic barrier function, and increased epithelial cell proliferation and cytokine expression (such as the proinflammatory chemokine interleukin-8). Together, the data suggest that in some hosts, ETBF acts via secretion of BFT to induce colitis. However, the full spectrum of clinical disease related to ETBF and the impact of chronic ETBF colonization on the host remain to be defined.

Citing Articles

Advances in gut microbiota-related treatment strategies for managing colorectal cancer in humans.

Roy B, Cao K, Singh C, Fang X, Yang H, Wei D Cancer Biol Med. 2025; 22(2).

PMID: 40072039 PMC: 11899591. DOI: 10.20892/j.issn.2095-3941.2024.0263.

Implications of intratumoral microbiota in tumor metastasis: a special perspective of microorganisms in tumorigenesis and clinical therapeutics.

Zhang L, Duan X, Zhao Y, Zhang D, Zhang Y Front Immunol. 2025; 16:1526589.

PMID: 39995663 PMC: 11847830. DOI: 10.3389/fimmu.2025.1526589.

Interplay of m6A RNA methylation and gut microbiota in modulating gut injury.

Wang H, Han J, Zhang X Gut Microbes. 2025; 17(1):2467213.

PMID: 39960310 PMC: 11834532. DOI: 10.1080/19490976.2025.2467213.

Tumor microbiome: roles in tumor initiation, progression, and therapy.

Zhang S, Huang J, Jiang Z, Tong H, Ma X, Liu Y Mol Biomed. 2025; 6(1):9.

PMID: 39921821 PMC: 11807048. DOI: 10.1186/s43556-025-00248-9.

Gut microbial composition associated with risk of premature aging in women with Yin-deficiency constitution.

Zhai Y, Li J, Cao Y, Li Y, Bao X, Liang J Front Cell Infect Microbiol. 2025; 14():1500959.

PMID: 39831109 PMC: 11739288. DOI: 10.3389/fcimb.2024.1500959.

References

Qadri F, Mohi M, Chowdhury A, Alam K, Azim T, Sears C . Monoclonal antibodies to the enterotoxin of Bacteroides fragilis: production, characterization, and immunodiagnostic application. Clin Diagn Lab Immunol. 1996; 3(5):608-10. PMC: 170417. DOI: 10.1128/cdli.3.5.608-610.1996. View

Gutacker M, Valsangiacomo C, Piffaretti J . Identification of two genetic groups in Bacteroides fragilis by multilocus enzyme electrophoresis: distribution of antibiotic resistance (cfiA, cepA) and enterotoxin (bft) encoding genes. Microbiology (Reading). 2000; 146 ( Pt 5):1241-1254. DOI: 10.1099/00221287-146-5-1241. View

Salyers A . Bacteroides of the human lower intestinal tract. Annu Rev Microbiol. 1984; 38:293-313. DOI: 10.1146/annurev.mi.38.100184.001453. View

Claros M, Claros Z, Hecht D, Citron D, Goldstein E, Silva Jr J . Characterization of the Bacteroides fragilis pathogenicity island in human blood culture isolates. Anaerobe. 2006; 12(1):17-22. DOI: 10.1016/j.anaerobe.2005.06.005. View

McIver K, Kessler E, Olson J, Ohman D . The elastase propeptide functions as an intramolecular chaperone required for elastase activity and secretion in Pseudomonas aeruginosa. Mol Microbiol. 1995; 18(5):877-89. DOI: 10.1111/j.1365-2958.1995.18050877.x. View

Hooper L, Gordon J . Commensal host-bacterial relationships in the gut. Science. 2001; 292(5519):1115-8. DOI: 10.1126/science.1058709. View

Riegler M, Lotz M, Sears C, Pothoulakis C, Castagliuolo I, Wang C . Bacteroides fragilis toxin 2 damages human colonic mucosa in vitro. Gut. 1999; 44(4):504-10. PMC: 1727476. DOI: 10.1136/gut.44.4.504. View

Basset C, Holton J, Bazeos A, Vaira D, Bloom S . Are Helicobacter species and enterotoxigenic Bacteroides fragilis involved in inflammatory bowel disease?. Dig Dis Sci. 2004; 49(9):1425-32. DOI: 10.1023/b:ddas.0000042241.13489.88. View

Saidi R, Sears C . Bacteroides fragilis toxin rapidly intoxicates human intestinal epithelial cells (HT29/C1) in vitro. Infect Immun. 1996; 64(12):5029-34. PMC: 174484. DOI: 10.1128/iai.64.12.5029-5034.1996. View

10.

Shetab R, Cohen S, Prindiville T, Tang Y, Cantrell M, Rahmani D . Detection of Bacteroides fragilis enterotoxin gene by PCR. J Clin Microbiol. 1998; 36(6):1729-32. PMC: 104908. DOI: 10.1128/JCM.36.6.1729-1732.1998. View

11.

Myers L, Shoop D, FIREHAMMER B, Border M . Association of enterotoxigenic Bacteroides fragilis with diarrheal disease in calves. J Infect Dis. 1985; 152(6):1344-7. PMC: 7110030. DOI: 10.1093/infdis/152.6.1344. View

12.

Kato N, Kato H, Watanabe K, Ueno K . Association of enterotoxigenic Bacteroides fragilis with bacteremia. Clin Infect Dis. 1996; 23 Suppl 1:S83-6. DOI: 10.1093/clinids/23.supplement_1.s83. View

13.

Antunes E, Ferreira E, Falcao L, Paula G, Avelar K, Barroso D . Non-toxigenic pattern II and III Bacteroides fragilis strains: coexistence in the same host. Res Microbiol. 2004; 155(7):522-4. DOI: 10.1016/j.resmic.2004.04.008. View

14.

Krzyzanowsky F, Avila-Campos M . Detection of non-enterotoxigenic and enterotoxigenic Bacteroides fragilis in stool samples from children in São Paulo, Brazil. Rev Inst Med Trop Sao Paulo. 2003; 45(4):225-7. DOI: 10.1590/s0036-46652003000400010. View

15.

Pantosti A, Cerquetti M, Colangeli R, DAmbrosio F . Detection of intestinal and extra-intestinal strains of enterotoxigenic Bacteroides fragilis by the HT-29 cytotoxicity assay. J Med Microbiol. 1994; 41(3):191-6. DOI: 10.1099/00222615-41-3-191. View

16.

Saidi R, Jaeger K, Montrose M, Wu S, Sears C . Bacteroides fragilis toxin rearranges the actin cytoskeleton of HT29/C1 cells without direct proteolysis of actin or decrease in F-actin content. Cell Motil Cytoskeleton. 1997; 37(2):159-65. DOI: 10.1002/(SICI)1097-0169(1997)37:2<159::AID-CM8>3.0.CO;2-3. View

17.

Holton J . Enterotoxigenic Bacteroides fragilis. Curr Infect Dis Rep. 2008; 10(2):99-104. DOI: 10.1007/s11908-008-0018-7. View

18.

Moore W, Holdeman L . Human fecal flora: the normal flora of 20 Japanese-Hawaiians. Appl Microbiol. 1974; 27(5):961-79. PMC: 380185. DOI: 10.1128/am.27.5.961-979.1974. View

19.

Kato N, Liu C, Kato H, Watanabe K, Nakamura H, Iwai N . Prevalence of enterotoxigenic Bacteroides fragilis in children with diarrhea in Japan. J Clin Microbiol. 1999; 37(3):801-3. PMC: 84562. DOI: 10.1128/JCM.37.3.801-803.1999. View

20.

Pathela P, Zahid Hasan K, Roy E, Alam K, Huq F, Siddique A . Enterotoxigenic Bacteroides fragilis-associated diarrhea in children 0-2 years of age in rural Bangladesh. J Infect Dis. 2005; 191(8):1245-52. DOI: 10.1086/428947. View