Evaluation of the Pathogenicity of the Bacteroides fragilis Toxin Gene Subtypes in Gnotobiotic Mice

Abstract

Enterotoxigenic Bacteroides fragilis (ETBF) strains produce a metalloprotease toxin (BFT) related to diarrheal disease in animals, young children, and adults. Three different isoforms of the enterotoxin, designated BFT-1, BFT-2, and BFT-3, have been identified and sequenced. In the present study, the pathogenicity of the ETBF strains carrying bft-1 or bft-2 was evaluated. Each toxin gene subtype of ETBF (bft-1 or bft-2) was intragastrically monoassociated to germ-free mice during 10 days and histopathological data from intestines and liver compared with those from mice monoassociated to a non-enterotoxigenic B. fragilis. Histopathological alterations were observed in all groups of animals related to ETBF. These alterations were characterized mainly by ulceration, edema, and inflammatory infiltration in intestine. However, these lesions were slightly more severe in mice monoassociated with bft-2 subtype. No alteration or lesion was observed in animals associated with the non-enterotoxigenic B. fragilis. In conclusion, strains harboring bft-1 or bft-2 gene subtypes were able to induce histopathological alterations in intestine of a gnotobiotic mice model and it could explain the effect produced for the enterotoxin.

Induction of Persistent Colitis by a Human Commensal, Enterotoxigenic Bacteroides fragilis , in Wild-Type C57BL/6 Mice

“…Recently, Nakano et al (31) reported that outbred germfree NIH (Swiss Webster) mice housed under short-term germfree conditions and infected with a human strain of WT-ETBF developed only mild, nonlethal colitis. Potential reasons for the experimental discrepancies include differences in susceptibility to colitis by different mouse strains and different amounts of BFT secretion among clinical strains of ETBF (4,43,53).…”

“…Recently, we described that ETBF colonization in C57BL/6J mice results in early colitis (by 1 to 2 weeks) and augments dextran sodium sulfate (DSS)-induced colitis (37). One brief study limited to histopathology reported that ETBF induces mild colitis in outbred germfree mice (31). Pharmacologic doses of BFT are reported to induce fluid accumulation in ligated murine intestinal loops (17).…”

EnterotoxigenicBacteroides fragilis: a Rogue among Symbiotes

“…Recently, colonization of gnotobiotic mice with ETBF, but not NTBF, has been shown to induce acute, sometimes lethal, colitis (71,92). In contrast, conventional mice colonized with ETBF develop rapid-onset, transient diarrhea lasting 3 to 4 days.…”

Distribution, detection of enterotoxigenic strains and antimicrobial drug susceptibility patterns of Bacteroides fragilis group in diarrheic and non-diarrheic feces from Brazilian infants

“…However, many cases of diarrhea are not diagnosed, due to mild and self-limited manifestations for which the patients do not seek medical service, or because there is an overload on the public health services, which makes the use of the available medical and laboratory resources difficult (21). Furthermore, there is a lack of scientific data on the incidence and the epidemiology of these diseases, which may interfere with public health policies, especially in developing countries.…”