Bacteroides fragilis is a species of anaerobic bacteria which lives in the colon of humans and animals. It makes up only about 1% of the human colonic flora, however, it is the most commonly isolated anaerobe from abscesses and soft tissue infections. Recent reports have shown that certain strains of B. fragilis produce an enterotoxin, suggesting a new role for this organism as an enteropathogen as well as evidence for a new virulence factor involved in its pathogenicity in tissues. This toxin has been implicated as a cause of diarrhea in several species of farm animals and more recently in humans, particularly infants. In preliminary studies, it appears that about 10% of isolates produce the toxin, suggesting that it is present in the colon in many individuals over long periods of time. The activity of the toxin was first discovered in the mid-1980's using the ligated ileal loop assay in lambs. Then, in 1990, it was shown that the activity could be detected by tissue culture assay using HT-29 colon carcinoma cells. We have now purified the toxin to homogeneity and showed that the enterotoxic activity observed in the lamb ligated loop assay and the cytotoxic activity (i.e., rounding of HT-29 cells) is due to the same protein. We have characterized the toxin, which has an M of about 20,000 and determined a partial N-terminal amino acid sequence. We are now cloning and sequencing the toxin gene, and studying its receptors and mechanism of action. We are also making specific polyclonal and monoclonal antibodies against the toxin to develop specific ELISA assays for detecting the toxin in feces and other clinical samples. This will establish a firm base for future collaborations with clinical investigators to determine the role of this toxin in etiology of diarrheal and infectious diseases and to determine approaches to diagnosis, therapy and treatment.
| Kling, J J; Wright, R L; Moncrief, J S et al. (1997) Cloning and characterization of the gene for the metalloprotease enterotoxin of Bacteroides fragilis. FEMS Microbiol Lett 146:279-84 |
