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PubMed1956

On the specificity of the desoxyribonucleic acid which induces streptomycin resistance in Hemophilus.

Streptomycin resistance of a high degree has been induced in sensitive populations of Hemophilus influenzae and Hemophilus parainfluenzae by desoxyribonucleic acids (DNA's) derived from streptomycin (SM)-resistant cells of at least one heterologous species of Hemophilus. The specificity of the DNA which controls SM resistance has been studied within and among species of Hemophilus by comparing, in a given population, the proportion of cells transformed to SM-resistant by DNA's derived from highly resistant cells of heterologous type or species with the proportion changed by the DNA derived from SM-resistant cells of the homologous type or species. The ratio resulting from this comparison correlates in general with the degree of kinship between recipient and donor cells suggested by accepted methods of bacteriologic classification. The numerical value of the ratio is much lower when the species of the recipient population and donor of the DNA differ than when they are of the same species. The data suggest that this ratio is of value as an index of degree of kinship of recipient and donor cells. Comparison of the activity of heterologous and homologous DNA's shows differences within species and degrees of differences among species not brought out by other available methods. The data suggest that H. influenzae is more closely related to H. parainfluenzae than to H. suis and that the relationship between H. parainfluenzae and H. suis is remote. Within the species H. influenzae and H. parainfluenzae the ratio of hetero-specific transformants to homospecific transformants appears to be relatively constant for a given recipient population. This ratio also appears to be independent of the type or group source of the heterologous species SM resistance DNA. The low proportion of cells in H. influenzae populations which are transformed to SM-resistant by DNA's derived from SM-resistant H. parainfluenzae and vice versa has been increased 4- to 15-fold by the replication of the heterologous species SM resistance DNA in the heterologous species. An alteration of the heterologous DNA by the host is suggested.

DNA↗
PubMed1956

Fate of Mycobacterium tuberculosis in mouse tissues as determined by the microbial enumeration technique. I. The persistence of drug-susceptible tubercle bacilli in the tissues despite prolonged antimicrobial therapy.

Observations are presented on the behavior of populations of tubercle bacilli in the tissues of mice during the administration of antimicrobial drugs. The behavior of the populations during therapy with any particular drug was different depending upon whether the tubercle bacilli were subsisting in the lung or in the spleen. Moreover, the pattern of microbial behavior was distinctive and predictable for each drug studied. Changes in the size of the populations of tubercle bacilli in the tissues appeared to be a more sensitive reflection of drug influence than microscopic study of the number and character of the tuberculous lesions. Nevertheless, in untreated animals, pulmonary lesions evolved and progressed steadily to a fatal outcome despite the fact that the populations of tubercle bacilli had stabilized at a relatively high census early in the course of therapy. The uniform persistence of tubercle bacilli in the spleen throughout prolonged drug administration was demonstrated with every drug or multiple drug regimens except for pyrazinamide when accompanied by isoniazid. Cultures of the bacilli which survived in the tissues despite antimicrobial therapy were highly susceptible to the drugs employed when tested in vitro. Thus the survival of the tubercle bacilli in the tissues represented microbial persistence rather than drug resistance. When pyrazinamide and isoniazid were administered together, it was not possible to detect the microorganisms in the spleen or lungs of treated animals. A detailed investigation of this apparent abolition of microbial persistence forms the subject of an accompanying report.

Aminosalicylic Acid↗
PubMed1957

The effect of x-rays on the rickettsiostatic activity of streptomycin, aureomycin, and penicillin.

The effect of x-rays on the rickettsiostatic activity of streptomycin, penicillin and aureomycin in the embryonate egg was investigated. Only a slight reversal of the rickettsiostatic action of 5 mg. of streptomycin occurred in embryonate eggs given 100 r of x-rays at 4 days of incubation, whereas complete reversal occurred in those given 1000 r. Groups of eggs irradiated with intermediate doses of x-rays showed a graded response. The rickettsiostatic activity of 5 mg. (1660 Oxford units/mg.) of penicillin or of 5 mg. of aureomycin was not reversed by doses of x-rays ranging from 100 to 1000 r. 500 r of x-rays reversed the rickettsiostatic activity of 2 mg., 4 mg., 8 mg., or 16 mg. of streptomycin per egg in proportion to the amount of streptomycin injected. The rickettsiostatic activity of 2 mg. of streptomycin was completely reversed and the activity of 16 mg. only partially reversed. Reversal of the rickettsiostatic activity of streptomycin by x-rays was observed when radiation was given up to 6 days after the injection of the antibiotic into 7-day-old embryos. Reversal of the rickettsiostatic activity of 4 mg. of streptomycin could be detected when the antibiotic was injected 3 days after 500 r of x-radiation. Explanations of the observed phenomena are discussed in terms of biochemical and biophysical alterations of the cells of the host.

Anti-Bacterial Agents↗
PubMed1952

The lysis in rabbits of intravascular blood clots by the streptococcal fibrinolytic system (streptokinase).

1. Based upon quantitative estimations of the factors that promote or retard the development and activity of the streptococcal fibrinolytic phenomenon, an active lytic system was developed within the circulating blood stream of rabbits following the intravenous infusion of streptokinase. During the infusion of adequate doses of SK, an active lytic system was observed to be present within 30 minutes following the beginning of the experiment and remained present for periods of time ranging from 1 to 20 hours depending primarily upon the concentration of SK and the duration of the infusion. Some of the biochemical changes accompanying the lytic system in vivo were: (a) a striking fall in the plasminogen; (b) a moderate fall in the serum inhibitor and the fibrinogen; and, (c) a rise in the acid-soluble nitrogen. These changes were usually self-terminating within 24 hours following the infusion of SK. In earlier studies similar trends were observed in the chest fluid of patients with hemothorax and empyema treated locally with streptokinase (22). 2. Intravascular clots, induced artificially by local applications of sodium morrhuate within the ear vein of the rabbits, were observed to liquefy and disappear in 23 of 25 rabbits during the intravenous infusion of SK into the opposite ear. The average quantity of SK necessary to effect an active lytic system was found to be about 40,000 units per kilo per hour. The clot in the ear vein was observed to be lysed completely in periods of time ranging from 3 to 7 hours after the infusion of SK was begun. Maintenance of an active lytic system for 3 to 4 additional hours was required to prevent re-formation of the clots at the original site. In 3 of 4 rabbits in which clots did reform, ACTH had been given to combat the toxic effects of the streptococcal concentrates. 3. The toxicity of the unusually large dose of the streptococcal concentrates, containing measured amounts of SK, along with other identifiable and unknown substances, was considerable, inasmuch as 8 animals eventually died. No evidence of pulmonary infarction was observed at autopsy. The administration of ACTH appeared to prevent a fatal outcome in at least 3 of the rabbits. Further studies of toxicity are in progress.

Animals↗
PubMed1953

Induction of streptomycin resistance in sensitive Hemophilus influenzae by extracts containing desoxyribonucleic acid from resistant Hemophilus influenzae.

Resistance to streptomycin, of a degree exceeding 1000 microg. per ml., has been induced in sensitive strains of Hemophilus influenzae by exposure for 10 minutes to desoxyribonucleic acid-containing extracts isolated from a strain of type b Hemophilus influenzae which had emerged resistant to 1000 microg. of streptomycin per ml. DNA is essential for the process which brings out this change; the reaction can be prevented by destruction of the DNA with crystalline desoxyribonuclease.The resistant trait which is created in this way is heritable. The nature of the process which induces resistance is similar in all respects to the reaction which induces heritable changes in type specificity of H. influenzae. These results offer another example of the gene-like action of highly specific DNA's. The pattern of resistance brought out in a bacterial population exposed to the DNA-containing, resistance-inducing extract, is similar to that which occurs when emergence of resistance of H. influenzae to streptomycin follows the selection by streptomycin of spontaneously occurring resistant mutants. The change in a bacterial cell from average susceptibility to streptomycin to resistance to 1000 microg. of streptomycin per ml. can occur in a single step.

DNA↗