Journal of Okayama Medical Association
Published by Okayama Medical Association

Full-text articles are available 3 years after publication.

結核菌のストレプトマイシン耐性に関する研究 第2編 ストレプトマイシン耐性結核菌の耐性持続性並びに緩解に就いて

Nozaki, Tatsuo
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In 1887, Kossiakoff first described the phenomenon of drug-resistance of bacteria. Recently with the wide-spread use of streptomycin and other various antibiotics in the field of therapeutics, this phenomenon of drug-resistance has become very important in clinical medicine. As to streptomycin alone, which was discovered in 1944 by Waksmann and brought the epoch-making progress to the therapy ef tuberculosis, the acquisition of resistance is one of the problems which need great precautions at the execution of streptomycin-therapy. Since 1946 when Luria and Delbrück first reported about the mechanism of acquisition of resistance to sulfonamide, the mechanism of acquisition of resistance to streptomycin and other antibiotics and that of reversion from it have been hotly argued. No decidedly substantiating results, however, have yet been obtained, though two confronting theories, spotaneous mutation theory and adaptation theory, are now advocated. The former is the theory which asserts that the acquisition of resistance is originated in their spontaneous mutation happening during the process of proliferation and in the selective action of drugs; this theory has nowadays many sustaining scholars. In the latter theory, the direct action of drugs to the rise of resistance is considered as the mehanism of the acquisition of resistance. Now that this phenomenon of drug-resistance is demonstrated to be the genetic variation with heredity and its mode of transmission is also clarified by Lederberg and Newcombe, it is difficult to explain the mechanism of acquisition of resistance according to the adaptation theory only. In the adaptation theory, however, refering to the idea of “Dauermodifikation” described on paramecium by Jollos in 1921, they have become to consider that antibiotics have the mutagenicity which seems to be the direct cause of the acquisition of drug-resistance. Since 1952, the author has carried out many experiments to study the essential features of streptomycin-resistant tubercle bacilli in vitro and in vivo, according to the "theory of spontaneous mutation with selection" which is supported by many researchers. The results are as follows: 1) Wolinsky reported that mutants over 0.1% of the original streptomycin-sensitive tubercle bacilli were observed on the culture media containig 1000γ/cc of streptomycin. In the present reports, the author studied the development of resistance by succesive cultures of the strains newly isolated from the tnberculosis patients who had received no or little streptomycin-therapy, and observed the spontaneous mutants over 0.1% of 0.1 mg and 1 mg of the inoculated bacilli. 2) Akiba et al. reported that, besides the spontaneous mutation, streptomycin itself had some effect on the mutation of gene. In the present work, many facts were observed which were hardly explained by “spontaneous mutation with selection” only. For example, the author also isolated one strain which seemed to be caused by such cause as that Akiba et al. reported. 3) There are many reports that the resistance of streptomycin-resistant tubercle bacilli is stable and long-lasting. The author performed many experiments in vitro and in vivo to study the development of the resistance of highly resistant strain over 1000γ/cc, of middle grade-resistant one over 100γ/cc and of low grade-resistant one under 10γ/cc. As a result of these experiments, the falling tendency of resistance was clearly observed in not only low and middle grade-resistant but also in highly resistant strains.