As reported by Umezawa1,2) among substances exhibiting inhibition against experimental animal tumors there are those which did not inhibit growth of tumor cells in tissue culture. These substances were considered to exhibit the antitumor effect in vivo after they had converted to an active form in vivo or to influence the host and indirectly to exhibit inhibition of tumor growth. As examples of the latter, Umezawa reported a polysaccharide of bacteria which showed inhibition against ascites type of Ehrlich carcmoma. Peptimycin presented in this paper is also another example. It exhibited inhibition against both ascites and solid types of Ehrlich carcinoma, but it did not inhibit HeLa cells and it did not exhibit destruction on Ehrlich carcinoma cells, when these cells were suspended in solution of this substance. This substance was isolated, found to be a peptide and named peptimycin.
This paper presents production, isolation, properties and biological activities of peptimycin.
Nucleoside antibiotics, angustmycins A and C1–3), were observed to exhibit inhibitory activity against experimental infections and transplantable tumors in animals4). Their in vitro antimicrobial activities were demonstrated in synthetic media, but they were markedly decreased in organic media5,6). Their activities were reversed by guanine, guanosine, adenosine, inosine, xanthosine and other related substances5). These results as well as their chemical structures2,3) suggested that angustmycins may act as antimetabolites in nucleic acid biosynthesis. The influence of angustmycins on 32P and 14C-labeled amino acids incorporations of Bacillus subtilis was investigated and the results are described in this report.
Blasticidin S, a water-soluble and basic antibiotic active against certain genera of bacteria and fungi, was isolated in crystalline form and characterized in our laboratory1). It is especially effective against Piricularia oryzae in the field as well as in vitro, which is a causative agent of the most drastic rice plant disease in Japan. The antibiotic was, found to exhibit a considerable effect against transplantable animal tumors, although it is highly toxic to animals. It was also confirmed that this substance contains cytosine in the molecule. Cytomycin, a cytosine-containing component, was obtained by mild alkaline hydrolysis of blasticidin S or from the culture filtrate of the producing organism2). Cytomycin was observed to have low toxicity and to be active against transplantable animal tumors. However, there seems to be a large difference in the weight of the effective doses of these antibiotics. The details of the results are described in this publication.
The study of the mode of action of streptomycin on the sensitive bacterial cells has revealed a multiplicity of effects on the bacterial metabolism1–4). With the accumulation of such informations, the usual question arises as to whether one is dealing with a, direct effect of the antibiotic on the metabolic activity under investigation, or whether instead these are secondary effects in dying cell. The difficulty of distinguishing between a biochemical change which is a direct effect of the antibiotic, and a secondary effect in a damaged cell continues complicate the interpretation of the data. To evaluate these experimental data on the metabolic effect of streptomycin in relation to its cytotoxic action, it becomes necessary to establish certain criteria for judgement of the significance, of these observations. The following criteria were selected by Oginsky5).
(1) The metabolic effects should be induced by the minimal concentrations of streptomycin effective in bacteriostasis.
(2) Only the antibiotically active derivatives of streptomycin should produce such effects.
(3) The phenomenon should be specific to streptomycin, as distinguished from other antibiotics.
(4) The reactions involved should be of vital importance to the economy of the cell.
In this paper, investigation has been undertaken in order to ascertain whether the, effect of dihydrostreptomycin upon the oxidative decomposition of α-ketoglutarate would appear to be in agreement with the described criteria.
There is various informations on the inhibitory action of oxytetracycline and chlortetracycline upon the bacterial metabolism. The following reactions are reported to be inhibited by oxytetracycline and chlortetracycline; the respiration system1–5), the oxidative phosphorylation system6-8), the formation of adaptive enzyme9), the metabolism of nucleic acid10–13), the oxidation of amino acid2,14), the reduction of nitrite15–16) and the activity of metal-protein 17).
The experiments presented in this paper, are concerned with the effect of oxytetracycline and chlortetracycline on the aerobic carbohydrate metabolism by the sensitive bacteria of coli-aerogenes.
In our laboratory, primary screening procedure to find out antibacterial streptomyces has been carried out on the solid agar from 1956 to 1958. Firstly, isolated organisms were streaked out on glycerol-meat extract-peptone agar plate and after 4-day incubation at 27°C, agar piece of definite size just beneath the grown colony was cut out and transferred on the center of freshly prepared nutrient agar plate. Secondly, several indicator organisms were streaked around this agar piece, and the activities of this agar piece against these organisms were examined. Thus potent strains were selected primarily and then the culture filtrates of these organisms were obtained in 4 different media under shaking condition, for secondary screening purpose.
The strain K-288 was quite particular during these examinations because it showed fairly high activity against gram positive organisms in the primary screening procedure described above but the activity was hardly detectable in the secondary screening, in spite of repeated examinations in different media. Thus the explanation of this inconformity was thought to be a matter of interest and several experiments have been conducted. Finally, the mass production of the active principle found at the time of primary screening was achieved only by a surface culture of the organism.
The procedure described above may suggest a new approach to find out a new antibiotic which will be hardly found under usual submerged cultures. However, the present report chiefly concerns with biological and chemical properties of the final product obtained from this filtrate together with the taxonomic characteristics of the strain K-288. As a result, the antibiotic K-288 was found to be closely related to vancomycin1,2). The strain K-288, however, was quite different from the known vancomycin producing strain, Streptomyces orientalis3).
Recently, with the introduction of various new antibiotics, a great advance has been made in the therapeutic field. However, on the other hand, the appearance of drug-resistance has posed a difficult problem, and 1s drawing much attention. The new antibiotic kanamycin (KM) discovered by Umezawa1)et al., is not an exception, and the relation between KM-resistance and streptomycin (SM)-resistance has been the subject of investigation by many researchers. However, their results are not always consistent. We think that this disparity of reasults is due to the fact that these investigators did not use the pure clone of the resistant mutants.
In order to clarify this relation between KM-resistance and SM-resistance, we have, checked the purity of resistant clones by the agar plating method at each step of resistance increase, and studies were made with these pure clones.
In a previous report the author reported analytical studies on the cross resistance of Escherichia coli B/r strain to kanamycin (KM) and streptomycin (SM). The present paper will undertake to analyze the results of experiment on the cross resistance between KM and SM in staphylococci.