Clostridium histolyticum

Clostridium histolyticum is a species of bacteria found in feces and the soil. It is a motile, gram-positive, aerotolerant anaerobe. C. histolyticum is pathogenic in many species, including guinea pigs, mice, and rabbits, and humans. C. histolyticum has been shown to cause gas gangrene, often in association with other bacteria species. In 1916, Weinberg and Séguin isolated this bacterium from patients with gas gangrene and called it Bacillus histolyticus. They discovered this bacterium was pathogenic for guinea pigs, mice, and rabbits, but less so for rats. Intramuscular injection of culture caused extensive local tissue destruction, extrusion of a hemorrhagic muscle pulp, splitting of the skin, denudation of the bone, and sometimes autoamputation. In 1922, Heller renamed the bacterium Weinbergillus histolyticus, and a year later Bergey, Harrison, et al. reclassified it as Clostridium histolyticum. Clostridium histolyticum can be isolated from soil during the early stage of soil cultivation, by heating the sample at 60 °C for 30 minutes. C. histolyticum can be plated on Zeissler plate agar, and appear as dewlike colonies of either rough or smooth morphology, surrounded by a zone of weak hemolysis. On blood agar, colonies appear small, rough, irregularly round, and are surrounded by a zone of weak hemolysis. These bacteria tend to clump in pairs or short chains and are rods of 3-5μm x 0.5-0.7μm. Cells are richly flagellate and very motile. Clostridium histolyticum produces large endospores and are asaccharolytic and proteolytic. This bacterium is anaerobic, however minimal growth may be obtained through aerobic culture. Clostridium histolyticum is difficult to culture because growth is inhibited by sugars, and spores are not very heat resistant. In wound smears, C. histolyticum closely resembles C. perfringens, but without the capsule of C. perfringens. This may interfere with diagnosis of C. histolyticum infection. Studies have shown that the toxigenicity of a strain of Clostridium histolyticum is directly related to its sporulating potency: the higher the sporulating potency, the more toxigenic the strain. Additionally, toxigenic strains possess a stronger potential for growth than less toxigenic or nontoxigenic strains. Smooth substrains of C. histolyticum seem to show higher toxigenicity than rough substrains. Clostridium histolyticum produces five toxins: alpha, beta, gamma, delta, and epsilon. The alpha-toxin is the major toxigenic factor of C. histolyticum. When injected into muscle, it can cause death in laboratory animals within hours. Alpha-toxin is a necrotizing, but not hemolytic, toxin. This toxin is secreted, as it is isolated from filtrates of C. histolyticum cultures. It is neutralized by antisera produced against toxic filtrates of C. septicum cultures through cross-neutralization. Additionally, alpha-toxin is readily inactivated by proteolytic enzymes. It has been shown that only about 29% of C. histolyticum strains isolated from soil actually produce this alpha-toxin. The beta-toxin of C. histolyticum is a group of seven collagenases. Collagenases are zinc metalloproteases that cleave collagen and gelatin into small fragments. The seven collagenases are alpha, beta, gamma, delta, epsilon, zeta, and eta. They are further identified by their molecular masses (68, 115,79,110, 125, and 130 kDa, respectively) to distinguish them from the five toxins. Beta-toxin plays a major role in the pathogenicity of C. histolyticum, due to its ability to destroy collagen fibers in the body and cause necrosis. Beta-toxin has been shown to induce hemorrhage when placed on the surface of lungs of animals, hemorrhage and edema when injected into rat paws, and lethal intrapulmonary hemorrhage when injected intravenously into animals.