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R DUBOS

Publications and source records attributed to R DUBOS.

17 recordsLinked to original sources

THE DEVELOPMENT OF THE BACTERIAL FLORA IN THE GASTROINTESTINAL TRACT OF MICE.

Selective culture media, and equipment for anaerobic incubation of large numbers of specimens, have been developed to facilitate the quantitative enumeration of the various aerobic and anaerobic bacterial species present in the gastrointestinal tract. The evolution of this flora has been followed in young mice from several colonies by cultivating homogenates of the different parts of the gastrointestinal tract at daily intervals from the time of birth to the time of weaning. It has been found that the lactobacilli and anaerobic streptococci become established immediately after birth and persist in large numbers, not only in the large intestine but also in the stomach and in the small intestine. In contrast, the anaerobic bacilli of the bacteroides group become established only after the 16th day; they multiply only in the large intestine but persist in this organ in very large numbers. Other bacterial species become established at different periods of time after birth, exhibit characteristic anatomic localizations, and greatly fluctuate in numbers. In general, the populations of enterobacilli and enterococci decrease precipitously after having reached a maximum level shortly after the beginning of colonization.

Animals↗

INDIGENOUS, NORMAL, AND AUTOCHTHONOUS FLORA OF THE GASTROINTESTINAL TRACT.

The bacterial flora of the gastrointestinal tract differs qualitatively and quantitatively from one colony of mice to another. Certain components of this flora, however, are always present in large and approximately constant numbers in healthy adult mice, irrespective of the colony from which the animals are derived. Lactobacilli and anaerobic streptococci are extremely numerous in the stomach, the small intestine, and the large intestine. In contrast, organisms of the bacteroides group proliferate only in the large intestine. These three bacterial species persist at approximately constant levels in their characteristic localization throughout the life span of healthy animals. They are closely associated with the walls of the digestive organs, and are probably concentrated in the mucous layer. A few experiments carried out with rats and young swine indicate that lactobacilli are also present in large numbers in the stomach of these animal species. It is suggested that some of the components of the gastrointestinal flora have become symbiotic with their hosts in the course of evolutionary development and thus constitute a true autochthonous flora. The other components of the indigenous flora are acquired early in life either through accidental contact or because they are ubiquitous in the environment. The "normal" flora is that which is always present in the environment of the animal colony under consideration.

Animals↗

A GENETIC STUDY OF SUSCEPTIBILITY TO EXPERIMENTAL TUBERCULOSIS IN MICE INFECTED WITH MAMMALIAN TUBERCLE BACILLI.

A study has been made of the genetic aspects of the difference between two inbred strains of mice (C57B1/6 and Swiss) in response to experimental infection with mammalian tubercle bacilli. Males and females, 4 to 6 weeks of age were inoculated intravenously with 0.2 ml of a 1/50 culture dilution of Mycobacterium tuberculosis var. bovis (Vallée strain) grown in tween albumin medium. Mean survival time for C57B1 animals was 28.1 +/- 0.6 days and for Swiss, 55.3 +/- 0.6 days postinfection. The characteristic survival time of the two strains was reversed in mice receiving a smaller infective dose. The age of mice at the time of inoculation also affected the results of infection: both C57B1 and Swiss, inoculated at 12 months of age, died at the same rate, but when inoculated at older ages, C57B1 survived slightly longer. Bacteriologic studies demonstrated that there was no significant difference between the two mouse strains with regard to the numbers of viable units of tubercle bacilli recovered from various organs during the 2 week period following infection with a 10(-3) culture dilution of Vallée. Moreover, the standard infective inoculum (1/50 culture dilution) did not activate corynebacterial pseudotuberculosis in C57B1 mice, a strain known to be latently infected with Corynebacterium kutscheri, rapid multiplication of tubercle bacilli occurred, but no corynebacteria were recovered. When C57B1 and Swiss strains were crossed, survival tests after infection with the standard inoculum demonstrated that mice of the F(1) generation were more resistant than either parent. Whether the overdominance was due to a new combination of parental genes for resistance or to heterosis was not determined. The increased litter size of the F(1) mice, an evidence of increased vigor, supports the view that heterosis was involved. In backcrosses to the resistant strain (Swiss), survival time gradually became stabilized at approximately the parental level. In the 1st backcross to the susceptible strain (C57B1), survival times fell into two classes indicating segregation of genes, with perhaps dominance of genes from the Swiss. After repeated backcrosses to C57B1, mice of the 4th backcross generation had a survival time essentially the same as that of the original parental strain. On the basis of having obtained progeny characterized by the original parental susceptibilities after genetic tendencies had been intermingled by crossbreeding, it was concluded that hereditary factors influenced the response of mice to experimental infection with M. tuberculosis. The number of genes was not determined.

Animals↗

CORYNEBACTERIAL PSEUDOTUBERCULOSIS IN MICE. I. COMPARATIVE SUSCEPTIBILITY OF MOUSE STRAINS TO EXPERIMENTAL INFECTION WITH CORYNEBACTERIUM KUTSCHERI.

The susceptibility of mice to experimental infection with Corynebacterium kutscheri was studied by comparing the host response to this organism of mice obtained from 31 different colonies, representing 15 different genetic types. A standardized infective dose, administered intravenously, made it possible to separate the animals into two sharply differentiated groups. All the animals of the following colonies died: Swiss Lynch, Swiss R/J, A/Jax, Princeton, RFVL, and CF(1) (SPF). All the animals of the following colonies survived: CFW, ICR, Balb/C, BSVS, BRVR, RIII, YBR/He, DBA/2 (from 3 different colonies), and C57B1/6 (from 12 different colonies). The two highly inbred strains, Swiss Lynch and C57Bl/6, were selected as prototypes of susceptible and resistant animals respectively, for more detailed studies. Following injection of an infective dose of 0.2 x 10(-4) ml of culture of C. kutscheri, all Swiss Lynch animals died within 3 to 11 days (the majority within 4 to 7 days); whereas all C57Bl/6 animals survived. The outcome of the infection in each strain was independent of age and sex of the animals. In Swiss Lynch animals, the corynebacteria multiplied rapidly in lungs, liver, kidneys, and to some extent in the spleen. In C57Bl/6 mice, there was no increase of the corynebacterial population in the lungs, liver, or spleen, but multiplication occurred in the kidneys during the early phase of the infectious process with resultant abscess formation. However, the renal infection soon subsided leaving no residual pathology. C. kutscheri could not be recovered from any organs of C57Bl/6 mice sacrificed 16 days after infection. Homogenates of organs from Swiss Lynch mice obtained while the infection was progressing contained only typical C. kutscheri. In contrast, the lungs and livers of similarly infected C57Bl/6 animals occasionally yielded large numbers of small translucent colonies distinctly different from those of typical corynebacteria. The use of mouse strains differing markedly in response to experimental infection with C. kutscheri is presented as a biologic model lending itself to further studies concerning factors which condition resistance to corynebacterial pseudotuberculosis, a disease of practical importance for investigators conducting experiments with murine species.

Allergy and Immunology↗

CORYNEBACTERIAL PSEUDOTUBERCULOSIS IN MICE. II. ACTIVATION OF NATURAL AND EXPERIMENTAL LATENT INFECTIONS.

Latent corynebactenai infection occurs naturally in many strains of mice. It can be evoked into the active disease, pseudotuberculosis, by a single injection of 10 mg of cortisone. The cortisone effect was tested in 21 colonies, representing 11 genetically different strains of mice. Animals of the C57B1/6, DBA/2, and RIII strains were shown to be latently infected with Corynebacterium kutscheri by the fact that they developed fatal pseudotuberculosis following cortisone treatment. Virulent C. kutscheri could not be isolated from homogenates of organs obtained from latently infected animals before cortisone administration; however, these homogenates yielded small translucent colonies of avirulent organisms. Recovery of these atypical colonies was facilitated by preincubating the organ homogenates before plating. The organisms constituting such colonies differed morphologically and immunologically from C. kutscheri, but had similar biochemical properties with the exception that they lacked urease and catalase activity. Mice treated with cortisone yielded both the avirulent bacteria and virulent C. kutscheri. The latter was the predominant organism present in the organs at the height of infection. Injection of avirulent organisms into Swiss Lynch mice, which are normally free of latent corynebacteria, occasionally established a latent infection which could be converted into corynebacterial pseudotuberculosis by cortisone. Cultures of fully virulent C. kutscheri were then obtained from the lesions. Latency was produced experimentally with a streptomycin-resistant strain of virulent C. kutscheri (CKsr) derived from the stock culture. When sublethal doses of CKsr were injected into NCS mice (Institut Pasteur colony), they induced a latent infection characterized by the presence of avirulent organisms possessing the streptomycin resistance marker. These were isolated in the form of small translucent colonies from the livers of the infected animals. Administration of cortisone to these animals subsequently evoked active infection from which virulent CKsr could be obtained. Injection of the avirulent streptomycin-resistant organisms into normal NCS mice established a latent infection which could be uniformly converted into corynebacterial pseudotuberculosis by cortisone. The virulent C. kutscheri obtained from the lesions bore the genetic marker of streptomycin resistance, thus being identical with CKsr. Except for streptomycin resistance, the avirulent organisms isolated from the experimentally induced latent infections were identical with those found in the naturally occurring latent infections. These results suggest that C. kutscheri can persist in vitro in an avirulent form which is resistant to the defense mechanisms of the host, and can thus establish a latent infection. Treatment of the animal with cortisone results in the conversion of the avirulent form into virulent C. kutscheri, and of the latent infection into active corynebacterial pseudotuberculosis. The findings are discussed with regard to their relevance to infection immunity, and to the conversion of latent infection into overt disease.

Allergy and Immunology↗

Measurement of resistance to experimental tuberculosis in mice.

NCS mice were found to be susceptible to a hyperacute form of disease induced by injection of relatively large doses of Mycobacterium tuberculosis. Susceptibility to this type of disease was conditioned by the sex, age, and dietary history of the animals. Unlike the more usual response of mice to mycobacterial disease, these conditions affected primarily the relative occurrence of early-acute deaths rather than average survival time. Resistance to this form of disease was increased by previous exposure of the animals to Gram-negative bacteria, to their endotoxin, or to various preparations of killed mycobacterial cells.

Animals↗