Okamoto and Suzuki1) reported that a multiple drug resistant E. coli K12 (R-5) produces an enzyme inactivating kanamycin. The strain used by these authors was obtained by transmission of an R-factor (R-5) from a naturally isolated drug resistant strain of Shigella sonnei2) which was resistant to chloramphenicol, tetracycline, dihydrostreptomycin, sulphanilamides and kanamycin. These authors suggested that the enzyme obtained from this strain would acetylate and inactivate kanamycin, because of the requirement of coenzyme A and acetate for the inactivation. Umezawa, Okanishi, Utahara, Maeda and Kondo8) have isolated the inactivated kanamycin and determined that amino group of 6-amino-6-deoxy-D-glucose moiety of kanamycin is acetylated.
As determined by Murase4), kanamycin C has glucosamine(2-amino-2-deoxy-D-glucose) instead of 6-amino-6-deoxy-D-glucose and this structure suggests that kanamycin C would show a different attitude to the inactivation by the cell-free system of the kanamycin resistant strain. Structural relations among kanamycins, paromomycins and neomycins stimulated us to study relations between the resistances and inactivations. In this paper, studies on the resistances of E. coli to these antibiotics and on the inactivation of these antibiotics by the cell-free system of these strains are described. An observation on resistance of S. sonnei is added.
Bleomycin discovered by Umezawa et al.1) is separated into bleomycin A and B, and these antibiotics, as reported by these authors in another paper2), are further separated into six components of bleomycin A and five components of bleomycin B. Ishizuka et al.3) reported the antitumor and antibacterial activity of each bleomycin, and the antitumor effect, toxicity, excretion and distribution of bleomycin A complex. These authors found that when bleomycin A complex was injected twice a week to dogs, the toxicity appeared in the reduction of liver function which was reversible. Recently, Ichikawa and his associates4) observed a marked effect of bleomycin A complex on a human skin cancer.
In dogs which were injected with bleomycin A complex twice a week and which showed no toxic sign in function of liver, kidney and hematopoetic organs, the falling out of hair and inflammation on foot pad were observed by Ishizuka et al.3). These phenomena and the effect on human skin cancer suggest a high distribution of bleomycin A complex in the skin. Therefore, the distribution of bleomycin A complex in lung, kidney and skin and the toxic sign in skin and nails of animals were studied in detail. In this paper, the toxic appearance in mouse nail and the concentrations in skin and other organs are reported together with some observations on antimicrobial activity, subacute toxicity of bleomycin A complex.
Fusidic and helvolinic acids, steroidal antibiotics of protolanostane skeleton, exhibit an antibacterial activity against gram-positive organisms. The molecular mechanism of action of both antibiotics has been investigated and the inhibition of protein synthesis has been observed. The results, concerning the inhibition of protein synthesis in the growing cells and in the cell-free systems directed by native messengers or by polyuridylate, have been presented in the previous paper1). Harvey et al. have recently reported the inhibition of protein synthesis by fusidic acid2).
The mechanism of action of the steroidal antibiotics has been further studied, in reference to the detailed site of action in the protein-synthesizing systems, and the results are presented in this publication.
Primocarcin is an antibiotic which has antitumor effect and antimicrobial activities. Primocarcin, firstly reported by Sumiki et al.1), is the product of Nocardia fukayae Nagatsu et al2). We have recently isolated independently primocarcin from the culture filtrate of a streptomycete which was isolated from a soil sample collected at Mori-machi, Shizuoka Prefecture, Japan.
From the taxonomic studies, the strain IN-701 was named Streptomyces diastatochromogenes var. luteus. The isolation procedures of primocarcin and taxonomic studies of the Streptomyces IN-701 are described in this report.
In our screenmg studies of macrolide antibiotics produced by soil actinomycetes, a new macrolide antibiotic was isolated from a culture broth of a strain, A 204-P2, which resembles Streptomyces narbonensis. The antibiotic has an absorption maximum at 232 mμ which is common among spiramycins, leucomycins and tertiomycins, and it is different
from narbomycin which shows a maximum at 225 mμo. The strain, A 204-P2, was classified as Streptomyces narbonensis var. josamyceticus nov. var., and produces the antibiotic as the main product which can easily be obtained as colorless needle crystals by the recrystallization from benzene. As presented in this paper, the antibiotic was differentiated from all known macrolide antibiotics and was named josamycin. In the present paper, characters of the source, isolation and characterization of josamycin are described.
Josamycin, a new macrolide antibiotic, was obtained from culture filtrate of Streptomyces narbonensis var. josamyceticus nov. var., and its isolation and physico-chemical properties were presented1). In this paper, results of biological studies on josamycin are described.