Cytotoxic Activity of Mycobacterium ulcerans

Although Mycobacterium ulcerans elicits extensive necrosis of human skin and subcutaneous tissue, the specific cause of the necrosis has never been elucidated. In an attempt to define a toxic substance, 18 strains of M. ulcerans were inoculated into mice, and the progress of each infection was observed and compared with infections of other mycobacteria, including M. cheloni, M. marinum, and M. bovis. Culture filtrates and viable organisms of each of these mycobacteria were inoculated onto tissue culture cells. Inoculation of mouse footpads with M. ulcerans resulted in progressive infections, leading to ulceration and eventual death. Strains of M. cheloni, M. marinum, and M. bovis did not produce progressive infections in the mice. Culture filtrates of M. ulcerans produced severe cytopathogenic effects on tissue cells, but washed, viable organisms of the same strains had no cytopathogenic effect. Culture filtrates and viable organisms of M. cheloni, M. marinum, and M. bovis did not produce a cytopathogenic effect on the tissue cells. Viable organisms of selected strains of M. ulcerans and the culture filtrates of the same strains were inoculated into guinea pig skin. The culture filtrates and the viable organisms both caused focal necrosis and focal inflammation, changes that resemble those in the naturally occurring infection in man. Preliminary purification of the culture filtrate by ultrafiltration indicates that the toxic fraction has a molecular weight of approximately 100,000, and temperature studies indicate that the toxic fraction is heat labile.