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R J DUBOS

Publications and source records attributed to R J DUBOS.

At least 73 records · Page 4Linked to original sources
PubMed1953

Multiplication and survival of tubercle bacilli in the organs of mice.

Cultures of tubercle bacilli (typical bovine and human strains) known to differ in the severity of the lesions they induce in experimental animals, were injected in various doses into the cerebrum, peritoneal cavity, or blood stream of mice. Quantitative determinations of the numbers of living bacilli present in the tissues at different intervals of time after infection led to the following classification of the cultures tested:- (a) Certain well known variant forms of tubercle bacilli were found to be unable to multiply in vivo, although they could survive for many weeks in the tissues of mice. These organisms proved to be truly avirulent. (b) Other variant forms underwent multiplication in vivo, even when extremely small infective doses were used, but could not give rise to progressive disease. It is proposed to designate these strains, which produce only abortive infections, as "attenuated." Different levels of attenuation could be detected. The maximum numbers of living bacilli that were recovered from the tissues corresponded directly to the severity and duration of the abortive lesions that could be produced by the strain in guinea pigs or in mice and were characteristic for each strain tested. The two BCG substrains tested were found to differ markedly in their level of attenuation. (c) The cultures virulent for guinea pigs were also capable of establishing a progressive infection in mice even when small infective doses were used. In the case of the attenuated and virulent strains, the population of living bacilli present in the lungs was at first much lower than that in the spleen, but it continued to increase in the former organs throughout the period of observation. This was notably true in the case of the virulent cultures. In contrast, the numbers of living bacilli in the spleen rapidly reached a maximum in the case of all cultures and then decreased progressively. For a given infective dose, and a given interval of time after inoculation, the maximum levels of living bacterial population attained in the spleen and in the lungs proved to be a direct expression of the virulence of the strain.

Animals↗
PubMed1953

Antituberculous immunity induced in mice by vaccination with living cultures of attenuated tubercle bacilli.

The immunity induced in mice by vaccination with living attenuated cultures of tubercle bacilli was measured by two criteria. (a) Increase in survival time of the vaccinated animals after infection with a dose of virulent bacilli sufficient to kill all the unvaccinated controls within 10 to 20 days. (b) Difference in the number of living bacilli recovered from the spleen and lungs of vaccinated and normal animals infected with a small dose of virulent bacilli. The level of immunity induced was found to depend upon the extent of multiplication in vivo of the bacilli used for vaccination. This in turn was conditioned by the degree of attenuation characteristic of the bacterial strain used in the preparation of the vaccine, the amount of vaccine injected, the route of vaccination, and the time interval between vaccination and challenge infection. It was possible to prevent or retard the development of immunity by treating the mice in course of immunization with a drug, isoniazid, capable of interrupting the multiplication in vivo of the bacilli used as vaccine. Although immunity regularly developed and lasted for many weeks when the proper conditions of vaccination were used, the immune response was never sufficient to protect the animals against ultimate death from infection with virulent tubercle bacilli. The prolongation of life in the vaccinated mice was not consequent on a direct bactericidal effect but rather on a retarded or interrupted multiplication of the virulent bacilli in vivo. The quantitative bacteriological techniques used in the present study would appear to be of value for the analysis of certain problems of immunity, and for the appraisal of vaccines and techniques of vaccination.

Animals↗
PubMed1953

Antituberculous immunity in mice vaccinated with killed tubercle bacilli.

The resistance of white mice to tuberculous infection could be increased by preliminary vaccination with small amounts of tubercle bacilli killed by contact with 2 per cent phenol. Vaccine prepared from a variant strain of human tubercle bacilli unable to multiply in vivo (H37Ra) proved as active as vaccines prepared from either virulent or attenuated strains. The immunity induced by phenol-killed bacilli persisted for several weeks. Under the conditions of the experiments, however, it was never able to bring about the death of the virulent bacilli used for the challenge infection, even when the infective inoculum was very small. Its protective effect could be detected (a) by the increased survival time of mice infected with a very large dose of virulent bacilli, and particularly (b) by the lower numbers of bacilli present in the organs of mice sacrificed at various periods of time after injection of sublethal infective doses. Under the proper conditions of vaccination the immunity produced in mice by phenol-killed cells of avirulent bacilli was of the same order as that produced by BCG. The protective antigen proved to be susceptible to heat, particularly at acid reactions. It retained its activity when the bacilli were disintegrated and rendered non-acid-fast by grinding with concentrated phenol. It remained in the insoluble cellular debris when the bacilli were extracted with 88 per cent phenol. Reasons are presented to support the view that the antigenic components present in the tubercle bacilli (avirulent as well as virulent) killed with phenol play a significant part in several manifestations of increased resistance to tuberculosis.

Animals↗
PubMed1953

Effect of the composition of the gaseous and aqueous environments on the survival of tubercle bacilli in vitro.

Tubercle bacilli die much more rapidly under anaerobic than under aerobic conditions. Anaerobically, the rate of death is accelerated by increased CO(2) pressure, and when certain metabolites (lactate for example) are present in the medium. Death of the bacilli under certain conditions of anaerobiosis is accompanied by loss of ability to take the acid-fast stain and by progressive cellular disintegration. These findings are discussed in relation to (a) the glycolytic equipment of tubercle bacilli, (b) their fate in tuberculous lesions.

Bacillus↗
PubMed1953

Effect of ketone bodies and other metabolites on the survival and multiplication of staphylococci and tubercle bacilli.

A study has been made of the fate of staphylococci and tubercle bacilli resuspended in aqueous media at slightly acid reactions. The tests were carried out at several acid reactions in balanced ionic media containing 0.5 per cent serum albumin. These experimental conditions were selected in order to approximate those which are probably encountered by pathogenic agents in inflammatory areas and in the intracellular environment of the leucocytes after phagocytosis. The viability of the microorganisms at a given pH was markedly influenced by the composition of the medium, being decreased by addition to the latter of lactic, acetic, propionic, and butyric acids, and increased by the addition of certain ketone bodies such as dihydroxyacetone and pyruvic, beta-hydroxybutyric, alpha-ketoglutaric, and oxalacetic acids. The presence of ketone bodies in the medium afforded to the microorganisms some protection against the bactericidal effect of lactic and acetic acids at acid reactions. The minimum and the optimum pH for growth were found to be dependent on the composition of the medium. Both were higher in the presence of lactic, acetic, propionic, and butyric acids than in the media without organic acids added. In contrast, the addition of ketone bodies to the medium allowed microbial multiplication even in acid media (approximately at pH 5.3 or even lower). The fact that lactic acid antagonizes, whereas ketone bodies favor, the survival and multiplication of staphylococci and tubercle bacilli at acid reactions, is discussed in relation to the high susceptibility to infection which is often associated with ketosis of various etiology.

Bacillus↗
PubMed1952

The effect of spermine on tubercle bacilli.

A crystalline substance capable of suppressing the growth of a variety of mycobacteria in vitro has been isolated from extracts of tissue in acidified dilute ethanol. This inhibitory material was found to be equally active against virulent, attenuated, and avirulent variants of human and bovine tubercle bacilli, but had little or no effect on saprophytic mycobacteria and on several non-acid-fast microorganisms under the conditions of the test. Its inhibitory activity on the growth of tubercle bacilli was essentially independent of the size of the inoculum within the limits studied. The crystalline material appeared to exert a bactericidal action on the susceptible organisms. Tubercle bacilli maintained in the presence of the agent for 4 days failed to grow when transferred to inhibitor-free media. The findings were not appreciably altered by minor variations in the composition of the medium or by shift in its reaction. When certain preparations of whole serum were used in the medium in place of albumin, no antimycobacterial activity was observed; however, this activity was restored by adding bovine albumin (fraction V) to the media containing whole serum. By chemical purification and analysis, the inhibitory material was identified as spermine, an organic base widely distributed in animal tissues.

Animals↗
PubMed1951

Variability of BCG strains (Bacillus Calmette-Guérin).

Three different cultures of BCG propagated for over 2 years in a liquid medium containing Tween 80 and albumin were found to differ in several of their intrinsic properties. Cultures of the three strains were found to consist of morphologically heterogeneous populations-each culture being made up of three main colonial types-spreading, intermediate, and non-spreading. The percentage distribution of colonial types was characteristic for each culture and remained constant during cultivation in liquid media. Injection of the various cultures into mice and guinea pigs resulted in a self-limited disease. The distribution, extent, and duration of the lesions were also characteristic for each culture. Both the spreading and non-spreading substrains derived from the various cultures exhibited the degree of attenuation of virulence characteristic of the parent strain.

Animals↗
PubMed1950

The effect of organic acids on mammalian tubercle bacilli.

The growth of tubercle bacilli in vitro was inhibited by the addition of the sodium salts of very low concentrations of certain organic acids to a variety of liquid and agar culture media containing whole serum or serum albumin. Capric acid was the most active of the compounds tested, but inhibition of growth occurred also with the shorter aliphatic acids. Lactic acid was also growth-inhibitory, whereas the keto and dicarboxylic acids tested were inactive in this respect. The inhibitory activity of the aliphatic acids and of lactic acid increased as the pH of the medium was lowered by addition of HCl. It was greater in media enriched with serum or with oleic acid-albumin complex, but was otherwise fairly independent of the composition of the medium. The inhibitory effect appears to be bacteriostatic rather than bactericidal and to depend upon a disturbance of the normal metabolic processes of the bacilli. Some of the long chain fatty acids caused a marked enhancement of growth when used in low concentrations and in admixture with enough serum albumin to overcome their toxicity. The significance of these findings is discussed with reference to the survival and multiplication of tubercle bacilli in vivo within inflammatory and caseous areas, which are known to be often acidic and to contain high concentrations of organic acids.

Acids↗