The human body comprises fewer host cells than bacterial cells, most of which are obligate anaerobes residing in the gut. The symbiont Bacteroides fragilis constitutes a relatively small proportion (up to 1%–2%) of cultured fecal bacteria, but colonizes most humans. There are 2 classes of B. fragilis distinguished by their ability to secrete a zinc-dependent metalloprotease toxin, B. fragilis toxin (BFT). Strains that do not secrete BFT are nontoxigenic B. fragilis (NTBF), and those that do are called enterotoxigenic B. fragilis (ETBF). ETBF can induce clinical pathology, including inflammatory diarrhea, although asymptomatic colonization may be common. Intestinal inflammation is mediated by BFT, as yet the only known virulence factor of ETBF. Recent experimental evidence demonstrating that ETBF-driven colitis promotes colon tumorigenesis has generated interest in the potential contribution of ETBF to human colon carcinogenesis. Critical questions about the epidemiology of chronic, subclinical human colonization with ETBF and its impact on the biology of the colon need to be addressed.
B. fragilis commonly colonize humans and are considered as 2 molecular types based on expression of BFT protein. NTBF is a human symbiont not associated with diarrheal disease, but able to cause invasive human disease. In contrast, ETBF is associated with diarrheal disease in all age groups and expresses 1 of 3 subtypes of BFT (BFT-1–BFT-3). BFT is a pre-proprotein toxin that is processed by ETBF to the secreted, mature 20-kDa protein toxin. Based on the HEXXH motif and other studies (69), the toxin is classified as a zinc-dependent metalloprotease toxin. BFT is related to other metalloprotease toxins important in human medicine, such as anthrax toxin, tetanus toxin, and botulinum toxin. Adapted with permission from Clinical Microbiology Reviews (6).