The bacillary cords characteristic for virulent tubercle bacilli are readily disrupted when wet bacilli are suspended in hydrocarbons such as paraffin oil or petroleum ether. The disruption of cords is due to the removal of a material coating the surface of the bacilli and causing them to adhere to each other. This material can be obtained from virulent bacilli by extracting them with petroleum ether. It is a lipid. Avirulent variants of tubercle bacilli do not yield a similar material after extraction in the same manner; only little of it is obtained from BCG bacilli. The following properties of the fraction obtained by petroleum ether extraction are described: (a) It inhibits the migration of leukocytes in vitro. (b) If repeatedly injected in small doses into mice, it is toxic, whereas a single high dose does not give rise to toxic manifestations. (c) The susceptibility of mice to the toxic action of repeated injections parallels to some extent their degree of susceptibility to infection with the strain of tubercle bacilli from which the fraction was obtained. (d) The injection of the extracted material into guinea pigs does not induce a state of allergic reactivity toward tuberculin. Likewise, tuberculin-positive guinea pigs do not show hypersensitivity against injections of the extracted substance. Bacilli extracted with petroleum ether do not lose their viability. They grow out normally in vitro, and they are still pathogenic. However, the removal of the petroleum ether-soluble lipid from the bacilli results in a loss of the ability of the organisms to inhibit the migration of polymorphonuclear leukocytes. Moreover, mice and guinea pigs infected with extracted bacilli may develop tuberculosis considerably slower than animals injected with comparable amounts of unextracted organisms. The significance of these findings is discussed in relation to the problem of the virulence of tubercle bacilli.

Alkanes↗

PubMed1950

Studies on the virulence of tubercle bacilli; the relationship of the physiological state of the organisms to their pathogenicity.

On the basis of earlier observations dealing with the relation of a petroleum ether-soluble material (cord factor) obtained from young cultures of virulent tubercle bacilli to the pathogenicity of these organisms, it was expected that young cultures yielding more cord factor than older ones of the same strain would also be more virulent for susceptible animals. By infecting mice with equal numbers of bacteria from 3 day and 3 week old cultures, significant differences in the character of disease produced were observed. The mice infected with the younger cultures died of a rapid, septicemic infection with tuberculous lesions in many organs including the heart. A tuberculous myocarditis was probably the immediate cause of death. Mice infected with the older bacteria died of a chronic disease corresponding to the well known mouse tuberculosis. In these cases, the heart was completely free of lesions. No histologic tissue reactions typical of tuberculosis were seen in the animals dying from the acute type of the disease. A similar rapidly progressing infection was observed in rabbits infected with bacteria from young cultures. The symptoms corresponded to the ones seen in the disease known as the Yersin type of tuberculosis. It seems that the pathology of this latter can be produced with every type of pathogenic mycobacteria, human as well as bovine and avian, provided the cultures used are young. Thus it may be inferred that the acute type of tuberculosis is more frequent than commonly accepted both in experimental infection and in the naturally occurring disease. It is proposed to explain the mechanism of this acute infection within the framework of the cord factor hypothesis.

Animals↗

PubMed1950