Bacteroides fragilis (Fig.20-3), the most important of all anaerobes because of its frequency of occurrence in clinical infection and its resistance to antimicrobial agents, is a Gram-negative bacillus with rounded ends 0.5 to 0.8 μm in diameter and 1.5 to 4.5 μm long. Most strains are encapsulated. Vacuolization or irregular staining is common, particularly in broth media. Some pleomorphism also may be seen. By electron microscopy, the ultrastructure of B fragilis is similar to that of other Gram-negative bacteria. The guanine-plus-cytosine content is 42 percent. Prevotella melaninogenica and Porphyromonas asaccharolytica are short to coccoid Gram- negative rods; they produce a distinctive pigment (brown to black), which is a heme derivative that colors the colony (Figs.20-4 and 20-5). Many strains of P melaninogenica require vitamin K, or similar compounds, as well as heme.

Numerous studies of the endotoxin of Gram-negative anaerobic bacilli have determined that the B fragilis endotoxin contains little or no lipid A, 2-ketodeoxyoctanate, or heptose. It also lacks β-hydroxymyristic acid. This endotoxin exhibits little biologic activity in various test systems and little chemotactic activity; what activity there is is complement-mediated by the alternative pathway. Poor biologic activity of endotoxin also has been demonstrated for the closely related species B thetaiotaomicron, B ovatus, B vulgatus, and B distasonis. Prevotella melaninogenica endotoxin contains no heptose or 2-ketodeoxyoctanate, and it and the endotoxin of P oralis both show weak biologic activity. Serologic methods have not been reliable for characterizing Gram-negative anaerobic rods.

Members of the genus Fusobacterium (Figs.20-6 and 20-7) may be spindle shaped or may have parallel sides and rounded ends. The guanine-plus-cytosine content ranges from 26 to 34 percent. Cells of F necrophorum often are elongated or filamentous, are curved, and possess spherical enlargements and large, free, round bodies. Fusobacterium nucleatum, although not producing infections as serious as those caused by F necrophorum, is a virulent organism and is much more common clinically. The cells of this species are usually spindle shaped, are 5 to 10 μm long, and are often seen in pairs, end to end.

The lipopolysaccharide of F necrophorum is located in a multilayered external coat. The endotoxin varies from strain to strain in its content of 2-ketodeoxyoctanate and sugars. Although biologic activity varies also, many strains do show strong biologic activity, comparable to that of Salmonella enteritidis. The endotoxin of F nucleatum also is variable in its biologic activity, but often exhibits strong activity, comparable to that of S enteritidis.

Bacteriophages active against B fragilis are not uncommon. They are species specific and active against most strains. Bacteriocins also are produced by strains of B fragilis and B thetaiotaomicron. Plasmids have been found in about half the Bacteroides strains studied. For the most part, the biologic and clinical significance of these plasmids is not known; however, some code for resistance to such antimicrobial agents as clindamycin, erythromycin, tetracycline, chloramphenicol, ampicillin, and cephalothin. Plasmid-mediated antibiotic resistance has been transferred from strains of B fragilis to other strains of this species, to B thetaiotaomicron, and to Escherichia coli. Such resistance also has been transferred from B distasonis to B fragilis.

Most strains of the B fragilis group can deconjugate bile acids and are equally active whether the bile acid is conjugated with glycine or with taurine. Rarely, P melaninogenica may deconjugate bile acids, but in general this species, P oralis, and F nucleatum are inhibited by bile acids and do not deconjugate them. Fusobacterium necrophorum also is active in deconjugating bile acids but is active primarily on taurine conjugates. A few strains of Gram-negative anaerobic bacilli can convert primary bile acids to secondary bile acids. Bacteroides thetaiotaomicron can convert some lithocholic acid to its ethyl ester. Because lithocholic acid is toxic in humans and has been shown to exert tumor-promoting activity in animals, this reaction may be important. Bacteroides fragilis hydrolyzes the conjugated metabolites of benzpyrene. Glucuronidase produced by anaerobic Gram-negative bacilli may be of special significance in deconjugating compounds that had previously been detoxified in the liver by combination with glucuronide. There is speculation that this enzyme may be important in promoting bowel cancer. The activity of B thetaiotaomicron, B distasonis, and other members of the B fragilis group against plant polysaccharides, chondroitin, and mucin may be a factor in colon cancer and other disorders. Dietary fiber consists primarily of plant cell wall polysaccharides that are not digested in the stomach or small bowel.

Certain Bacteroides species possess distinguishing enzymes. Superoxide dismutase has been found in B fragilis, B thetaiotaomicron, B vulgatus, and B ovatus. In general, a good correlation exists between superoxide dismutase activity and oxygen tolerance. No consistent relationship has been found between catalase activity and oxygen tolerance, however. β-Lactamase activity has been demonstrated in several Bacteroides species, some Prevotella, and Bilophila; it accounts for most of the resistance to various β-lactam antibiotics, such as penicillins and cephalosporins, although other mechanisms are responsible occasionally. Urease is produced by Bilophila wadsworthia and by Bacteroides ureolyticus. The latter organism also produces an agarase, which accounts for pitting of the agar by the colonies. A related pitting organism, Sutterella wadsworthensis, is much more pathogenic and is relatively resistant to antimicrobial agents.