Cord-forming property, lethality and pathogenicity of Mycobacteria.

The genus Mycobacterium include a great number of non-pathogenic organisms as well as some pathogenic species which cause tuberculosis in mammals, birds and cold-blooded animals. The differentiation between pathogenic strains and non-pathogenic ones is based on the lethal properties of the bacilli for experimental animals, particularly the guinea pig. A strain is not considered pathogenic when i t does not kill the animal, even when it causes considerable morbid lesions. This simple criterion of pathogenicity makes it possible to differentiate the lethal strains from non-pathogenic or saprophytic Mycobacteria but it does not enable to recognize the non-lethal strains of reduced or intermediate pathogenicity. I t was accepted by inference, that these latter strains are not of importance in human pathology. Interest in these strains was aroused recently when it was found that the cultures of acidfast bacilli from patients under streptomycin or isoniazid therapy are often not lethal to guinea pigs.=-" The discovery that these strains although not lethal to guinea pigs are lethal to mice (Karlson and Ikemi, 1952), that the BCG strain, which was thoroughly studied and recognized a s not lethal to animals and humans, has killed two men (Meyer and Jensen, 1954; Oeding and co-workers, 1954) further complicated the pathogenicity problem of Mycobacteria. The amount of lesions in animals cannot differentiate the strains of reduced pathogenicity. Other suggested procedures, such a s the inoculation of the chorioallantoic membrane of the developing chick embryo, have also failed to differentiate Mycobacteria of reduced pathogenicity (Fite and Olson, 1944). I n vitro methods would be of considerable advantage over animal inoculation in pathogenicity studies. They would save time and money and might eventually demonstrate the pathogenicity of Mycobacteria not revealed by animal inoculations. Middlebrook, Dubos and Pierce, 1947, recognized the "cord formation" in Mycobacteria a s an indicator of pathogenicity. These findings were confirmed by Roth, 1949, Bloch, 1950, and others. Doubts about the significance of "cord formation" as an indicator of pathogenicity were aroused when this kind of formation was found in seemingly non-lethal or even saprophytic strains of Mycobacteria, (Richmond and Cummings, 1950) and when photographs of BCG cords were published by Kolbel, 1951, Engbaek, 1952. These findings forced Dubos, 1950, to pose the question of how to reconcile the presence of cords and the absence of pathogenicity in Mycobacteria.