Shimi and Shoukry1) isolated a new antibiotic from metabolites of a strain of Streptomyces. Because of its polypeptide nature and the presence of iron and chlorine in its molecule the antibiotic was denoted ferramido chloromycin (FACM). The antimicrobial activities of FACM in combination with other antibiotics revealed some interesting findings which are described below.
The concentrated efforts in search for anticancer substance have been made in many laboratories. Our investigation along this line has led a finding of a protein1), designated as neocarzinostatin, in a culture filtrate of Streptomyces carzinostaticus. The production and preliminary characterization of the neocarzinostatin was reported previously1) and the study of the mechanism has revealed that the protein posesses a regulatory function of DNA metabolism; inhibition of DNA synthesis followed by DNA degradation2). On the contrary to mitomycin C, which exhibits analogous biochemical activity to the neocarzinostatin, the latter has much higher molecular weight of protein nature, and lower critical inhibitory concentration against DNA synthesis. Present paper describes further purification and characterization of the protein.
As described by Maeda, Kosaka, Yagishita And Umezawa1) and Takita, Maeda and Umezawa2), phleomycin is obtained as a blue powder containing copper from a culture filtrate of Streptomyces verticillus and it shows inhibition of growth of Gram positive and negative bacteria. Lein, Heinemann and Gourevitch3) found its effect of inducing lysogenic bacteria, and Bradner and Pindell4) and Umezawa, Hori, Ishizuka and Takeuchi5) found its inhibitory effect on tumors in mice and rats. Ikekawa, Iwami, Hiranaka and Umezawa6) tried the complete purification of this antibiotic and found that phleomycin were separated into 11 or 12 active components. Copper of phleomycin is removed by treatment with 8-hydroxyquinoline and the copper-free phleomycin was also found to have both antimicrobial and antitumor activities.
Tanaka, Yamaguchi and Umezawa7) found the inhibition of DNA synthesis by this antibiotic and Falashi and Kornberg8 found the selective inhibition of DNA polymerase. Thus, this antibiotic is suggested by its mode of action and its high therapeutic index against tumors in mice and rats to be an interesting antibiotic also in view point of cancer chemotherapy. In this paper, the antitumor activity, the antimicrobial activity and the toxicity of each component of phleomycin which has been obtained in a sufficient amount and those of phleomycin complex containing 11 components are presented.
It has long been known1,2) that the penicillin resistance of staphylococci isolated from pathological materials depends chiefly on the penicillinase produced by the cocci. Recently, Miyamura et al.,3, 4, 5) Chabbert6) et al. and Dunsmoor7) et al. disclosed that chloramphenicol resistance of Staphylococcus, Shigella and Escherichia coli isolated from pathological materials were closely related to the production of the enzyme inactivating chloramphenicol. In addition, nitrofuran derivatives8, 9) also reported to be inactivated by various species of bacteria.
The authors12) examined the relation between the MIC (minimum inhibitory concentration) value obtained by the agar dilution method and the ability to be inactivated by bacteria and found that in combinations of various bacteria and drugs the MIC value and the ability of inactivating drugs were not always parallel, the same MIC value sometimes
being associated with different ability to inactivate drugs.
In the treatment of infectious diseases, the ability of causative bacteria inactivating the drug used is naturally thought to have an influence on the clinical effect of the chemotherapy. Cosequently, the examinations of drug-inactivating ability of bacteria and the drug-sensitivity are considered to be greatly useful for the analysis of the chemotherapy, the estimation of clinical effects and the choice of drugs to be used.
Although the drug-inactivating ability of bacteria is being determined mostly by the test-tube method with liquid media, this method is too laborious to be done as a routine work in the clinical laboratory. In the present paper the authors intend to describe a simple method for the determination of drug-inactivating ability of bacteria which could simply be conducted as an application of the sensitivity disc method.
Little work has been reported on the action of antibiotics on muscle metabolism and presumably few problems have been encountered clinically in this regard, especially at the dosages generally employed. In the present study, various antibiotics have been screened up to very high or pharmacological levels on the oxygen and glucose uptakes and the glycogen content of the isolated rat diaphragm. Tests with kojic acid (5-hydroxy-2-(hydroxymethyl)-4-pyrone) and usnic acid, antibiotics elaborated by Aspergilli and lichens, respectively, in addition to sulfanilamide and the antituberculous drug, p-aminosalicylic acid (PAS), were also included.